The American Journal of Orthopedics

 Compartment syndrome (CS) is one of the true orthopedic emergencies. Identifying the high-risk patient, making a prompt diagnosis, and initiating effective treatment are the crucial steps in avoiding a poor outcome. A physician’s inability to communicate with young children can interfere with diagnosing CS in a timely fashion. Many young patients in hospitals are admitted to pediatric floors where routine orthopedic care is not the norm and staff are unfamiliar with the signs and symptoms of evolving CS. As orthopedic surgeons are often involved in caring for these patients, they should be aware of the aspects of CS that are unique to children and should be able to identify patients who are at risk and would benefit from close monitoring. In addition, given the consequences of late diagnosis, early diagnosis is important from a medicolegal standpoint. Only 44% of cases of adult and pediatric CS are decided in favor of treating physicians, compared with 75% of cases in other orthopedic malpractice claims.1,2

Risk Factors for Posttraumatic Compartment Syndrome

Supracondylar Humeral Fracture

CS is a well-described complication of this injury. CS develops in 0.1% to 0.3% of children who present with supracondylar humeral fracture.^3,4 Casted elbow flexion beyond 90° and concomitant vascular injury put these children at increased risk for CS. Mubarak and Carroll⁵ reported 9 cases of CS in the volar compartment of the forearm after an extension-type supracondylar humeral fracture and attributed 8 of them to elbow flexion beyond 90° after closed reduction. In 29 children with supracondylar humeral fracture,Battaglia and colleagues³ found the highest compartment pressure in the deep volar compartment, especially near the fracture site, as well as a significant increase in pressure with the elbow flexed beyond 90°.

In a study of children with supracondylar humeral fracture, Choi and colleagues⁶ found 2 cases of CS among 9 patients who presented with a pulseless, poorly perfused hand and no cases of CS among 24 patients who presented with a pulseless but well-perfused hand.

Studies have found that a treatment delay of 8 to 12 hours did not increase the rate of CS in Gartland type 2 and type 3 fractures.^7-10 The investigators in these studies did not recommend delaying treatment of patients with neurologic deficit and absent radial pulse. Ramachandran and colleagues4 reported 11 cases of CS in patients with low-energy supracondylar humeral fracture and intact radial pulse at presentation. The patients who developed CS presented with severe swelling, and their mean treatment delay was 22 hours (range, 6-64 hours). Given the data, we do not recommend delayed treatment for children with supracondylar humeral fracture and neurologic deficit or absent pulse. We do recommend close inpatient preoperative monitoring of patients with severe swelling.

CS after supracondylar humeral fracture is mostly seen in the volar compartment of the forearm, but it has also been reported in the mobile wad, the anterior arm compartment, and the posterior arm compartment.^11,12

Floating Elbow

CS has been reported in children with ipsilateral humeral and forearm fractures. Blakemore and colleagues¹³ reported a 33% rate of CS in children with displaced distal humeral and forearm fractures. A retrospective review of 16 cases of floating elbow treated at Boston Children’s Hospital found CS in 2 patients and incipient CS in 4 of 10 patients with forearm fractures treated with closed reduction and plaster casting. There were no signs of CS in 6 patients with distal humeral and forearm fractures stabilized with Kirschner wires.¹⁴ Given the data, we do not recommend circumferential casting for forearm fractures in children with floating elbow.

Forearm Fracture

Haasbeek and Cole¹⁵ reported CS in 5 (11%) of 46 children with open forearm fracture. Yuan and colleagues¹⁶ reported CS in 3 (6%) of 50 open forearm fractures and 3 of 30 closed fractures treated with closed reduction and intramedullary nailing. They found increased risk for CS in patients with longer operative time, indicating prolonged closed manipulation of these fractures as a risk factor for CS. They did not find any cases of CS among 205 forearm fractures treated with closed reduction and casting.

Flynn and colleagues17 reported CS in 2 of 30 patients treated with intramedullary nailing within 24 hours of injury and in 0 of 73 patients treated after 24 hours.

Blackman and colleagues¹⁸ reported CS in 3 (7.7%) of 39 open forearm fractures and 0 of 74 closed fractures treated operatively. In their series, a small incision was made to facilitate reduction in 38 (51.4%) of 74 closed fractures to decrease closed manipulation and operative time. The rate of CS after intramedullary nailing of closed forearm fractures was lower in this series than in similar reports in the literature.

Reported data indicate increased risk for CS in children with open forearm fractures and fractures treated with closed reduction and intramedullary nailing, especially performed within 24 hours of injury, and prolonged closed manipulation performed during surgery. We recommend close monitoring of all children with operatively treated forearm fractures and, in particular, children with the risk factors mentioned.

Femoral Fracture

Although CS after femoral shaft fractures is not common, CS has been reported after 90/90 spica casting of femoral shaft fractures in children. Mubarak and colleagues19 reported on 9 children who developed calf CS after treatment of femoral shaft fracture in 90/90 spica casts. The technique used in 7 of the 9 reported cases involved initial application of a short leg cast and then traction applied to the leg—believed to cause impinging of the cast on the posterior compartment of the leg. The authors recommended an alternative method of applying spica casts, which is beyond the scope of this review.

Tibial Fracture

Children with tibial fracture, especially a fracture sustained in a motor vehicle accident, are at risk for CS. Hope and Cole²⁰ found CS in 4 (4%) of 92 children with open tibial fracture.

Children with tibial tubercle fracture are at increased risk for CS because of concomitant vascular injury. Pandya and colleagues²¹ reported CS or vascular compromise in 4 of 40 patients with tibial tubercle fracture. We recommend close monitoring for signs of impending CS in children who present with high-energy tibial shaft fracture and tibial tubercle fracture.

Flynn and colleagues²² reported outcomes of 43 cases of acute CS of the leg in children treated at 2 pediatric trauma centers. Mean time from injury to fasciotomy was 20.5 hours (range, 3.9-118 hours). Functional outcome was excellent at time of follow-up; 41 of 43 cases had no sequelae, and the 2 patients who lost function underwent fasciotomy more than 80 hours after injury. Despite the long interval between injury and surgery, excellent results were achieved with fasciotomy, suggesting an increased potential for recovery in the pediatric population.

Mubarak²³ reported on 6 cases of distal tibial physis fracture in patients who presented with severe pain and swelling of the ankle, hyposthesia of the first web space, weakness of the extensor hallucis longus and extensor digitorum communis, and pain on passive flexion of the toes. In all these patients, intramuscular pressure was more than 40 mm Hg beneath the extensor retinaculum and less than 20 mm Hg in the anterior compartment. All patients experienced prompt relief of pain and improved sensation and strength within 24 hours after release of the superior extensor retinaculum and fracture stabilization.

Miscellaneous and Nontraumatic Causes of Compartment Syndrome

Neonatal CS is very rare, and diagnosis is often missed. Neonatal CS is thought to be caused by a combination of low neonatal blood pressure and birth trauma.²⁴ Ragland and colleagues²⁵ reported on 24 cases of neonatal CS; in only 1 case was the diagnosis made within 24 hours.They described a “sentinel skin lesion” on the forearm of each patient as the sign of neonatal CS. Late diagnosis results in contracture and growth arrest of the involved extremity. In their series, only 1 patient underwent fasciotomy within 24 hours, and it resulted in a good functional outcome. High clinical suspicion is the key to early diagnosis and treatment of this rare pathology.

Medical problems that cause intracompartmental bleeding (hepatic failure, renal failure, leukemia, hemophilia) have been cited as causing CS.^26-28 CS may be the first symptom of occult hemophilia²⁹ Correction of the coagulation defect may take priority over surgical treatment in these cases, though the decision should be made on a case-by-case basis.²⁶

CS in children can also be caused by snakebites. Shaw and Hosalkar³⁰ reported on successful use of antivenin in preventing the need for surgical treatment in 16 of 19 patients with rattlesnake bites. Two patients had limited surgical débridement, and 1 underwent fasciotomy for CS. The authors recommended using antivenin to prevent CS in children with snakebites.³⁰

Prasarn and colleagues² reported on 12 cases of upper extremity CS in children in the absence of fractures. Of the 12 patients, 10 were managed in an intensive care unit and had an obtunded sensorium. Etiology in 7 (58%) of the 12 cases was iatrogenic (intravenous infiltration, retained phlebotomy tourniquet). In this series, 4 amputations were performed on affected extremities.

Diagnosis

Identification of evolving CS in a child is difficult because of the child’s limited ability to communicate and anxiety about being examined by a stranger. Orthopedists are trained to look for the 5 Ps (pain, paresthesia, paralysis, pallor, pulselessness) associated with CS. Examining an anxious, frightened young child is difficult, and documenting the degree of pain is not practical in a child who may not be able or willing to communicate effectively.

In a series of 33 children with CS, Bae and colleagues³¹ found that the 5 Ps were relatively unreliable in making a timely diagnosis. The authors also found that increased analgesic use was documented a mean of 7.3 hours before a change in vascular status and that it was a more sensitive indicator of CS in children. The resulting recommendation is that children at risk for CS be closely monitored for the 3 As (increasing analgesic requirement, anxiety, agitation).³²

Regional anesthesia is used to control postoperative pain in adults and children.^33,34 Injudicious use may mask the primary symptom (pain) of CS.^32,35-38 Use of regional anesthesia in patients at high risk for CS is highly discouraged.

Although CS is a clinical diagnosis, compartment pressure measurements can be useful in making decisions in certain clinical scenarios. In an obtunded child or in a child with severe mental and communication disability, such a measurement can help confirm or rule out the diagnosis.

Normal compartment pressures are higher in children than in adults. Staudt and colleagues³⁹ compared pressures in 4 lower leg compartments of 20 healthy children and 20 healthy adults. Mean pressure varied from 13.3 mm Hg to 16.6 mm Hg in children and from 5.2 mm Hg to 9.7 mm Hg in adults—indicating higher normal pressure in lower leg compartments in children.

Compartment pressures were reported highest within 5 cm of the fracture site.⁴⁰ When clinically indicated, they should be measured in that area in an injured extremity. The pressure threshold that requires fasciotomy is debatable. Intracompartmental pressures of 30 to 45 mm Hg, or measurements less than 30 mm Hg of diastolic blood pressure (pressure change = diastolic blood pressure – compartment pressure), have been recommended as cutoffs by some authors.^41-44 As resting normal compartment pressures are higher in children, these cutoffs cannot be used as reliably in children as in adults. Direct measurement of intracompartmental pressure is invasive and can be difficult in an agitated, awake child. The potential utility of near-infrared spectroscopy in the diagnosis of increased compartment pressure has been reported.^45,46 This method uses differential light absorption properties of oxygenated hemoglobin to measure tissue ischemia—similar to the method used in pulse oximetry. Compared with pulse oximetry, near-infrared spectroscopy can sample deeper tissue (3 cm below skin level). Shuler and colleagues⁴⁵ reported near-infrared spectroscopy findings for 14 adults with acute CS. Lower tissue oxygenation levels correlated with increased intracompartmental pressures, but the authors could not define a cutoff for which near-infrared spectroscopy measurements would indicate significant tissue ischemia. Use of this method in diagnosing CS in children was described in a case report.⁴⁶

CS remains a clinical diagnosis. Informing family and staff about the signs and symptoms of this syndrome and closely monitoring analgesic use in these patients are crucial. Compartment pressure measurements can be used when the diagnosis is unclear, particularly in noncommunicative patients, but these values should be interpreted with caution.

Treatment

Once CS is diagnosed, emergent fasciotomy and decompression are indicated. Surgeons planning fasciotomy should be aware of the definitive treatment of the CS etiology. Treatment of clotting deficiency in cases caused by excessive bleeding, fracture fixation, and vascular repair may be indicated during fasciotomy and decompression.

Summary

Increased need for analgesics is often the first sign of CS in children and should be considered the sentinel alarm for ongoing tissue necrosis. CS remains a clinical diagnosis, and compartment pressure should be measured only as a confirmatory test in noncommunicative patients or when the diagnosis is unclear. Children with supracondylar humeral fractures, forearm fractures, tibial fractures, and medical risk factors for coagulopathy are at increased risk and should be monitored closely. When the diagnosis is made promptly and the condition is treated with fasciotomy, good long-term clinical results can be expected.

 Compartment syndrome (CS) is one of the true orthopedic emergencies. Identifying the high-risk patient, making a prompt diagnosis, and initiating effective treatment are the crucial steps in avoiding a poor outcome. A physician’s inability to communicate with young children can interfere with diagnosing CS in a timely fashion. Many young patients in hospitals are admitted to pediatric floors where routine orthopedic care is not the norm and staff are unfamiliar with the signs and symptoms of evolving CS. As orthopedic surgeons are often involved in caring for these patients, they should be aware of the aspects of CS that are unique to children and should be able to identify patients who are at risk and would benefit from close monitoring. In addition, given the consequences of late diagnosis, early diagnosis is important from a medicolegal standpoint. Only 44% of cases of adult and pediatric CS are decided in favor of treating physicians, compared with 75% of cases in other orthopedic malpractice claims.1,2

Risk Factors for Posttraumatic Compartment Syndrome

Supracondylar Humeral Fracture

CS is a well-described complication of this injury. CS develops in 0.1% to 0.3% of children who present with supracondylar humeral fracture.^3,4 Casted elbow flexion beyond 90° and concomitant vascular injury put these children at increased risk for CS. Mubarak and Carroll⁵ reported 9 cases of CS in the volar compartment of the forearm after an extension-type supracondylar humeral fracture and attributed 8 of them to elbow flexion beyond 90° after closed reduction. In 29 children with supracondylar humeral fracture,Battaglia and colleagues³ found the highest compartment pressure in the deep volar compartment, especially near the fracture site, as well as a significant increase in pressure with the elbow flexed beyond 90°.

In a study of children with supracondylar humeral fracture, Choi and colleagues⁶ found 2 cases of CS among 9 patients who presented with a pulseless, poorly perfused hand and no cases of CS among 24 patients who presented with a pulseless but well-perfused hand.

Studies have found that a treatment delay of 8 to 12 hours did not increase the rate of CS in Gartland type 2 and type 3 fractures.^7-10 The investigators in these studies did not recommend delaying treatment of patients with neurologic deficit and absent radial pulse. Ramachandran and colleagues4 reported 11 cases of CS in patients with low-energy supracondylar humeral fracture and intact radial pulse at presentation. The patients who developed CS presented with severe swelling, and their mean treatment delay was 22 hours (range, 6-64 hours). Given the data, we do not recommend delayed treatment for children with supracondylar humeral fracture and neurologic deficit or absent pulse. We do recommend close inpatient preoperative monitoring of patients with severe swelling.

CS after supracondylar humeral fracture is mostly seen in the volar compartment of the forearm, but it has also been reported in the mobile wad, the anterior arm compartment, and the posterior arm compartment.^11,12

Floating Elbow

CS has been reported in children with ipsilateral humeral and forearm fractures. Blakemore and colleagues¹³ reported a 33% rate of CS in children with displaced distal humeral and forearm fractures. A retrospective review of 16 cases of floating elbow treated at Boston Children’s Hospital found CS in 2 patients and incipient CS in 4 of 10 patients with forearm fractures treated with closed reduction and plaster casting. There were no signs of CS in 6 patients with distal humeral and forearm fractures stabilized with Kirschner wires.¹⁴ Given the data, we do not recommend circumferential casting for forearm fractures in children with floating elbow.

Forearm Fracture

Haasbeek and Cole¹⁵ reported CS in 5 (11%) of 46 children with open forearm fracture. Yuan and colleagues¹⁶ reported CS in 3 (6%) of 50 open forearm fractures and 3 of 30 closed fractures treated with closed reduction and intramedullary nailing. They found increased risk for CS in patients with longer operative time, indicating prolonged closed manipulation of these fractures as a risk factor for CS. They did not find any cases of CS among 205 forearm fractures treated with closed reduction and casting.

Flynn and colleagues17 reported CS in 2 of 30 patients treated with intramedullary nailing within 24 hours of injury and in 0 of 73 patients treated after 24 hours.

Blackman and colleagues¹⁸ reported CS in 3 (7.7%) of 39 open forearm fractures and 0 of 74 closed fractures treated operatively. In their series, a small incision was made to facilitate reduction in 38 (51.4%) of 74 closed fractures to decrease closed manipulation and operative time. The rate of CS after intramedullary nailing of closed forearm fractures was lower in this series than in similar reports in the literature.

Reported data indicate increased risk for CS in children with open forearm fractures and fractures treated with closed reduction and intramedullary nailing, especially performed within 24 hours of injury, and prolonged closed manipulation performed during surgery. We recommend close monitoring of all children with operatively treated forearm fractures and, in particular, children with the risk factors mentioned.

Femoral Fracture

Although CS after femoral shaft fractures is not common, CS has been reported after 90/90 spica casting of femoral shaft fractures in children. Mubarak and colleagues19 reported on 9 children who developed calf CS after treatment of femoral shaft fracture in 90/90 spica casts. The technique used in 7 of the 9 reported cases involved initial application of a short leg cast and then traction applied to the leg—believed to cause impinging of the cast on the posterior compartment of the leg. The authors recommended an alternative method of applying spica casts, which is beyond the scope of this review.

Tibial Fracture

Children with tibial fracture, especially a fracture sustained in a motor vehicle accident, are at risk for CS. Hope and Cole²⁰ found CS in 4 (4%) of 92 children with open tibial fracture.

Children with tibial tubercle fracture are at increased risk for CS because of concomitant vascular injury. Pandya and colleagues²¹ reported CS or vascular compromise in 4 of 40 patients with tibial tubercle fracture. We recommend close monitoring for signs of impending CS in children who present with high-energy tibial shaft fracture and tibial tubercle fracture.

Flynn and colleagues²² reported outcomes of 43 cases of acute CS of the leg in children treated at 2 pediatric trauma centers. Mean time from injury to fasciotomy was 20.5 hours (range, 3.9-118 hours). Functional outcome was excellent at time of follow-up; 41 of 43 cases had no sequelae, and the 2 patients who lost function underwent fasciotomy more than 80 hours after injury. Despite the long interval between injury and surgery, excellent results were achieved with fasciotomy, suggesting an increased potential for recovery in the pediatric population.

Mubarak²³ reported on 6 cases of distal tibial physis fracture in patients who presented with severe pain and swelling of the ankle, hyposthesia of the first web space, weakness of the extensor hallucis longus and extensor digitorum communis, and pain on passive flexion of the toes. In all these patients, intramuscular pressure was more than 40 mm Hg beneath the extensor retinaculum and less than 20 mm Hg in the anterior compartment. All patients experienced prompt relief of pain and improved sensation and strength within 24 hours after release of the superior extensor retinaculum and fracture stabilization.

Miscellaneous and Nontraumatic Causes of Compartment Syndrome

Neonatal CS is very rare, and diagnosis is often missed. Neonatal CS is thought to be caused by a combination of low neonatal blood pressure and birth trauma.²⁴ Ragland and colleagues²⁵ reported on 24 cases of neonatal CS; in only 1 case was the diagnosis made within 24 hours.They described a “sentinel skin lesion” on the forearm of each patient as the sign of neonatal CS. Late diagnosis results in contracture and growth arrest of the involved extremity. In their series, only 1 patient underwent fasciotomy within 24 hours, and it resulted in a good functional outcome. High clinical suspicion is the key to early diagnosis and treatment of this rare pathology.

Medical problems that cause intracompartmental bleeding (hepatic failure, renal failure, leukemia, hemophilia) have been cited as causing CS.^26-28 CS may be the first symptom of occult hemophilia²⁹ Correction of the coagulation defect may take priority over surgical treatment in these cases, though the decision should be made on a case-by-case basis.²⁶

CS in children can also be caused by snakebites. Shaw and Hosalkar³⁰ reported on successful use of antivenin in preventing the need for surgical treatment in 16 of 19 patients with rattlesnake bites. Two patients had limited surgical débridement, and 1 underwent fasciotomy for CS. The authors recommended using antivenin to prevent CS in children with snakebites.³⁰

Prasarn and colleagues² reported on 12 cases of upper extremity CS in children in the absence of fractures. Of the 12 patients, 10 were managed in an intensive care unit and had an obtunded sensorium. Etiology in 7 (58%) of the 12 cases was iatrogenic (intravenous infiltration, retained phlebotomy tourniquet). In this series, 4 amputations were performed on affected extremities.

Diagnosis

Identification of evolving CS in a child is difficult because of the child’s limited ability to communicate and anxiety about being examined by a stranger. Orthopedists are trained to look for the 5 Ps (pain, paresthesia, paralysis, pallor, pulselessness) associated with CS. Examining an anxious, frightened young child is difficult, and documenting the degree of pain is not practical in a child who may not be able or willing to communicate effectively.

In a series of 33 children with CS, Bae and colleagues³¹ found that the 5 Ps were relatively unreliable in making a timely diagnosis. The authors also found that increased analgesic use was documented a mean of 7.3 hours before a change in vascular status and that it was a more sensitive indicator of CS in children. The resulting recommendation is that children at risk for CS be closely monitored for the 3 As (increasing analgesic requirement, anxiety, agitation).³²

Regional anesthesia is used to control postoperative pain in adults and children.^33,34 Injudicious use may mask the primary symptom (pain) of CS.^32,35-38 Use of regional anesthesia in patients at high risk for CS is highly discouraged.

Although CS is a clinical diagnosis, compartment pressure measurements can be useful in making decisions in certain clinical scenarios. In an obtunded child or in a child with severe mental and communication disability, such a measurement can help confirm or rule out the diagnosis.

Normal compartment pressures are higher in children than in adults. Staudt and colleagues³⁹ compared pressures in 4 lower leg compartments of 20 healthy children and 20 healthy adults. Mean pressure varied from 13.3 mm Hg to 16.6 mm Hg in children and from 5.2 mm Hg to 9.7 mm Hg in adults—indicating higher normal pressure in lower leg compartments in children.

Compartment pressures were reported highest within 5 cm of the fracture site.⁴⁰ When clinically indicated, they should be measured in that area in an injured extremity. The pressure threshold that requires fasciotomy is debatable. Intracompartmental pressures of 30 to 45 mm Hg, or measurements less than 30 mm Hg of diastolic blood pressure (pressure change = diastolic blood pressure – compartment pressure), have been recommended as cutoffs by some authors.^41-44 As resting normal compartment pressures are higher in children, these cutoffs cannot be used as reliably in children as in adults. Direct measurement of intracompartmental pressure is invasive and can be difficult in an agitated, awake child. The potential utility of near-infrared spectroscopy in the diagnosis of increased compartment pressure has been reported.^45,46 This method uses differential light absorption properties of oxygenated hemoglobin to measure tissue ischemia—similar to the method used in pulse oximetry. Compared with pulse oximetry, near-infrared spectroscopy can sample deeper tissue (3 cm below skin level). Shuler and colleagues⁴⁵ reported near-infrared spectroscopy findings for 14 adults with acute CS. Lower tissue oxygenation levels correlated with increased intracompartmental pressures, but the authors could not define a cutoff for which near-infrared spectroscopy measurements would indicate significant tissue ischemia. Use of this method in diagnosing CS in children was described in a case report.⁴⁶

CS remains a clinical diagnosis. Informing family and staff about the signs and symptoms of this syndrome and closely monitoring analgesic use in these patients are crucial. Compartment pressure measurements can be used when the diagnosis is unclear, particularly in noncommunicative patients, but these values should be interpreted with caution.

Treatment

Once CS is diagnosed, emergent fasciotomy and decompression are indicated. Surgeons planning fasciotomy should be aware of the definitive treatment of the CS etiology. Treatment of clotting deficiency in cases caused by excessive bleeding, fracture fixation, and vascular repair may be indicated during fasciotomy and decompression.

Summary

Increased need for analgesics is often the first sign of CS in children and should be considered the sentinel alarm for ongoing tissue necrosis. CS remains a clinical diagnosis, and compartment pressure should be measured only as a confirmatory test in noncommunicative patients or when the diagnosis is unclear. Children with supracondylar humeral fractures, forearm fractures, tibial fractures, and medical risk factors for coagulopathy are at increased risk and should be monitored closely. When the diagnosis is made promptly and the condition is treated with fasciotomy, good long-term clinical results can be expected.

 Compartment syndrome (CS) is one of the true orthopedic emergencies. Identifying the high-risk patient, making a prompt diagnosis, and initiating effective treatment are the crucial steps in avoiding a poor outcome. A physician’s inability to communicate with young children can interfere with diagnosing CS in a timely fashion. Many young patients in hospitals are admitted to pediatric floors where routine orthopedic care is not the norm and staff are unfamiliar with the signs and symptoms of evolving CS. As orthopedic surgeons are often involved in caring for these patients, they should be aware of the aspects of CS that are unique to children and should be able to identify patients who are at risk and would benefit from close monitoring. In addition, given the consequences of late diagnosis, early diagnosis is important from a medicolegal standpoint. Only 44% of cases of adult and pediatric CS are decided in favor of treating physicians, compared with 75% of cases in other orthopedic malpractice claims.1,2

Risk Factors for Posttraumatic Compartment Syndrome

Supracondylar Humeral Fracture

CS is a well-described complication of this injury. CS develops in 0.1% to 0.3% of children who present with supracondylar humeral fracture.^3,4 Casted elbow flexion beyond 90° and concomitant vascular injury put these children at increased risk for CS. Mubarak and Carroll⁵ reported 9 cases of CS in the volar compartment of the forearm after an extension-type supracondylar humeral fracture and attributed 8 of them to elbow flexion beyond 90° after closed reduction. In 29 children with supracondylar humeral fracture,Battaglia and colleagues³ found the highest compartment pressure in the deep volar compartment, especially near the fracture site, as well as a significant increase in pressure with the elbow flexed beyond 90°.

In a study of children with supracondylar humeral fracture, Choi and colleagues⁶ found 2 cases of CS among 9 patients who presented with a pulseless, poorly perfused hand and no cases of CS among 24 patients who presented with a pulseless but well-perfused hand.

Studies have found that a treatment delay of 8 to 12 hours did not increase the rate of CS in Gartland type 2 and type 3 fractures.^7-10 The investigators in these studies did not recommend delaying treatment of patients with neurologic deficit and absent radial pulse. Ramachandran and colleagues4 reported 11 cases of CS in patients with low-energy supracondylar humeral fracture and intact radial pulse at presentation. The patients who developed CS presented with severe swelling, and their mean treatment delay was 22 hours (range, 6-64 hours). Given the data, we do not recommend delayed treatment for children with supracondylar humeral fracture and neurologic deficit or absent pulse. We do recommend close inpatient preoperative monitoring of patients with severe swelling.

CS after supracondylar humeral fracture is mostly seen in the volar compartment of the forearm, but it has also been reported in the mobile wad, the anterior arm compartment, and the posterior arm compartment.^11,12

Floating Elbow

CS has been reported in children with ipsilateral humeral and forearm fractures. Blakemore and colleagues¹³ reported a 33% rate of CS in children with displaced distal humeral and forearm fractures. A retrospective review of 16 cases of floating elbow treated at Boston Children’s Hospital found CS in 2 patients and incipient CS in 4 of 10 patients with forearm fractures treated with closed reduction and plaster casting. There were no signs of CS in 6 patients with distal humeral and forearm fractures stabilized with Kirschner wires.¹⁴ Given the data, we do not recommend circumferential casting for forearm fractures in children with floating elbow.

Forearm Fracture

Haasbeek and Cole¹⁵ reported CS in 5 (11%) of 46 children with open forearm fracture. Yuan and colleagues¹⁶ reported CS in 3 (6%) of 50 open forearm fractures and 3 of 30 closed fractures treated with closed reduction and intramedullary nailing. They found increased risk for CS in patients with longer operative time, indicating prolonged closed manipulation of these fractures as a risk factor for CS. They did not find any cases of CS among 205 forearm fractures treated with closed reduction and casting.

Flynn and colleagues17 reported CS in 2 of 30 patients treated with intramedullary nailing within 24 hours of injury and in 0 of 73 patients treated after 24 hours.

Blackman and colleagues¹⁸ reported CS in 3 (7.7%) of 39 open forearm fractures and 0 of 74 closed fractures treated operatively. In their series, a small incision was made to facilitate reduction in 38 (51.4%) of 74 closed fractures to decrease closed manipulation and operative time. The rate of CS after intramedullary nailing of closed forearm fractures was lower in this series than in similar reports in the literature.

Reported data indicate increased risk for CS in children with open forearm fractures and fractures treated with closed reduction and intramedullary nailing, especially performed within 24 hours of injury, and prolonged closed manipulation performed during surgery. We recommend close monitoring of all children with operatively treated forearm fractures and, in particular, children with the risk factors mentioned.

Femoral Fracture

Although CS after femoral shaft fractures is not common, CS has been reported after 90/90 spica casting of femoral shaft fractures in children. Mubarak and colleagues19 reported on 9 children who developed calf CS after treatment of femoral shaft fracture in 90/90 spica casts. The technique used in 7 of the 9 reported cases involved initial application of a short leg cast and then traction applied to the leg—believed to cause impinging of the cast on the posterior compartment of the leg. The authors recommended an alternative method of applying spica casts, which is beyond the scope of this review.

Tibial Fracture

Children with tibial fracture, especially a fracture sustained in a motor vehicle accident, are at risk for CS. Hope and Cole²⁰ found CS in 4 (4%) of 92 children with open tibial fracture.

Children with tibial tubercle fracture are at increased risk for CS because of concomitant vascular injury. Pandya and colleagues²¹ reported CS or vascular compromise in 4 of 40 patients with tibial tubercle fracture. We recommend close monitoring for signs of impending CS in children who present with high-energy tibial shaft fracture and tibial tubercle fracture.

Flynn and colleagues²² reported outcomes of 43 cases of acute CS of the leg in children treated at 2 pediatric trauma centers. Mean time from injury to fasciotomy was 20.5 hours (range, 3.9-118 hours). Functional outcome was excellent at time of follow-up; 41 of 43 cases had no sequelae, and the 2 patients who lost function underwent fasciotomy more than 80 hours after injury. Despite the long interval between injury and surgery, excellent results were achieved with fasciotomy, suggesting an increased potential for recovery in the pediatric population.

Mubarak²³ reported on 6 cases of distal tibial physis fracture in patients who presented with severe pain and swelling of the ankle, hyposthesia of the first web space, weakness of the extensor hallucis longus and extensor digitorum communis, and pain on passive flexion of the toes. In all these patients, intramuscular pressure was more than 40 mm Hg beneath the extensor retinaculum and less than 20 mm Hg in the anterior compartment. All patients experienced prompt relief of pain and improved sensation and strength within 24 hours after release of the superior extensor retinaculum and fracture stabilization.

Miscellaneous and Nontraumatic Causes of Compartment Syndrome

Neonatal CS is very rare, and diagnosis is often missed. Neonatal CS is thought to be caused by a combination of low neonatal blood pressure and birth trauma.²⁴ Ragland and colleagues²⁵ reported on 24 cases of neonatal CS; in only 1 case was the diagnosis made within 24 hours.They described a “sentinel skin lesion” on the forearm of each patient as the sign of neonatal CS. Late diagnosis results in contracture and growth arrest of the involved extremity. In their series, only 1 patient underwent fasciotomy within 24 hours, and it resulted in a good functional outcome. High clinical suspicion is the key to early diagnosis and treatment of this rare pathology.

Medical problems that cause intracompartmental bleeding (hepatic failure, renal failure, leukemia, hemophilia) have been cited as causing CS.^26-28 CS may be the first symptom of occult hemophilia²⁹ Correction of the coagulation defect may take priority over surgical treatment in these cases, though the decision should be made on a case-by-case basis.²⁶

CS in children can also be caused by snakebites. Shaw and Hosalkar³⁰ reported on successful use of antivenin in preventing the need for surgical treatment in 16 of 19 patients with rattlesnake bites. Two patients had limited surgical débridement, and 1 underwent fasciotomy for CS. The authors recommended using antivenin to prevent CS in children with snakebites.³⁰

Prasarn and colleagues² reported on 12 cases of upper extremity CS in children in the absence of fractures. Of the 12 patients, 10 were managed in an intensive care unit and had an obtunded sensorium. Etiology in 7 (58%) of the 12 cases was iatrogenic (intravenous infiltration, retained phlebotomy tourniquet). In this series, 4 amputations were performed on affected extremities.

Diagnosis

Identification of evolving CS in a child is difficult because of the child’s limited ability to communicate and anxiety about being examined by a stranger. Orthopedists are trained to look for the 5 Ps (pain, paresthesia, paralysis, pallor, pulselessness) associated with CS. Examining an anxious, frightened young child is difficult, and documenting the degree of pain is not practical in a child who may not be able or willing to communicate effectively.

In a series of 33 children with CS, Bae and colleagues³¹ found that the 5 Ps were relatively unreliable in making a timely diagnosis. The authors also found that increased analgesic use was documented a mean of 7.3 hours before a change in vascular status and that it was a more sensitive indicator of CS in children. The resulting recommendation is that children at risk for CS be closely monitored for the 3 As (increasing analgesic requirement, anxiety, agitation).³²

Regional anesthesia is used to control postoperative pain in adults and children.^33,34 Injudicious use may mask the primary symptom (pain) of CS.^32,35-38 Use of regional anesthesia in patients at high risk for CS is highly discouraged.

Although CS is a clinical diagnosis, compartment pressure measurements can be useful in making decisions in certain clinical scenarios. In an obtunded child or in a child with severe mental and communication disability, such a measurement can help confirm or rule out the diagnosis.

Normal compartment pressures are higher in children than in adults. Staudt and colleagues³⁹ compared pressures in 4 lower leg compartments of 20 healthy children and 20 healthy adults. Mean pressure varied from 13.3 mm Hg to 16.6 mm Hg in children and from 5.2 mm Hg to 9.7 mm Hg in adults—indicating higher normal pressure in lower leg compartments in children.

Compartment pressures were reported highest within 5 cm of the fracture site.⁴⁰ When clinically indicated, they should be measured in that area in an injured extremity. The pressure threshold that requires fasciotomy is debatable. Intracompartmental pressures of 30 to 45 mm Hg, or measurements less than 30 mm Hg of diastolic blood pressure (pressure change = diastolic blood pressure – compartment pressure), have been recommended as cutoffs by some authors.^41-44 As resting normal compartment pressures are higher in children, these cutoffs cannot be used as reliably in children as in adults. Direct measurement of intracompartmental pressure is invasive and can be difficult in an agitated, awake child. The potential utility of near-infrared spectroscopy in the diagnosis of increased compartment pressure has been reported.^45,46 This method uses differential light absorption properties of oxygenated hemoglobin to measure tissue ischemia—similar to the method used in pulse oximetry. Compared with pulse oximetry, near-infrared spectroscopy can sample deeper tissue (3 cm below skin level). Shuler and colleagues⁴⁵ reported near-infrared spectroscopy findings for 14 adults with acute CS. Lower tissue oxygenation levels correlated with increased intracompartmental pressures, but the authors could not define a cutoff for which near-infrared spectroscopy measurements would indicate significant tissue ischemia. Use of this method in diagnosing CS in children was described in a case report.⁴⁶

CS remains a clinical diagnosis. Informing family and staff about the signs and symptoms of this syndrome and closely monitoring analgesic use in these patients are crucial. Compartment pressure measurements can be used when the diagnosis is unclear, particularly in noncommunicative patients, but these values should be interpreted with caution.

Treatment

Once CS is diagnosed, emergent fasciotomy and decompression are indicated. Surgeons planning fasciotomy should be aware of the definitive treatment of the CS etiology. Treatment of clotting deficiency in cases caused by excessive bleeding, fracture fixation, and vascular repair may be indicated during fasciotomy and decompression.

Summary

Increased need for analgesics is often the first sign of CS in children and should be considered the sentinel alarm for ongoing tissue necrosis. CS remains a clinical diagnosis, and compartment pressure should be measured only as a confirmatory test in noncommunicative patients or when the diagnosis is unclear. Children with supracondylar humeral fractures, forearm fractures, tibial fractures, and medical risk factors for coagulopathy are at increased risk and should be monitored closely. When the diagnosis is made promptly and the condition is treated with fasciotomy, good long-term clinical results can be expected.

Blount disease (tibia vara) is an angular tibia deformity that includes varus, increased posterior slope, and internal rotation. This deformity was first described in 1922 by Erlacher1 in Germany. In 1937, Walter Blount2 reported on it in the United States. It is the most common cause of pathologic genu varum in adolescence and childhood.

An oblique incomplete closing wedge osteotomy of the proximal tibial metaphysis was described by Wagner³ for the treatment of unicompartmental osteoarthrosis of the knee in adults. Laurencin and colleagues⁴ applied this technique to the treatment of pediatric tibia vara with favorable results. They spared the medial cortex of the tibia in their incomplete closing wedge osteotomy technique. In each of the 9 cases we treated and describe here, we accidentally completed the tibial osteotomy when attempting the Laurencin technique. Given that the osteotomy was completed, we modified the Laurencin technique by using a 6-hole, 4.5-mm compression plate rather than a 5-hole semitubular plate, and added a large oblique screw from the medial side to compress the osteotomy site and to protect the plate from fracture. In addition, in 2 patients who weighed more than 250 pounds, we used an external fixator for additional stability. In this article, we report the outcomes of correcting adolescent tibia vara with a complete closing wedge tibial osteotomy and an oblique fibular osteotomy.

Materials and Methods

This study was approved by the Institutional Review Board at Pennsylvania State University. Between 2009 and 2012, we performed 9 complete oblique proximal tibial lateral closing wedge osteotomies on 8 patients (2 girls, 6 boys). In each case, the primary diagnosis was Blount disease. One patient also had renal dysplasia and was receiving dialysis. Mean age at time of operation was 15 years (range, 13-17 years). Mean preoperative weight was 215 pounds (range, 119-317 lb). Mean weight gain at follow-up was 4.39 pounds (range, –10 to 19 lb). Mean body mass index (BMI) was 38 (range, 25-48) (Table). All patients had varus angulation of the proximal tibia before surgery. Mean preoperative varus on standing films was 22° (range, 10°-36°). Because of the patients’ size, we used standing long-leg radiographs, on individual cassettes, for each leg.

Surgical Technique

Before surgery, we use paper cutouts to template the osteotomy wedge. We also use perioperative antibiotics and a standard time-out. For visualization of the entire leg for accurate correction, we prepare and drape the entire leg. A sterile tourniquet is used. At the midshaft of the fibula, a 4-cm incision is made, and dissection is carefully carried down to the fibula. Subperiosteal dissection is performed about the fibula, allowing adequate clearance for an oblique osteotomy. The osteotomy removes about 1 cm of fibula, which is to be used as bone graft for the tibial osteotomy. In addition, a lateral compartment fasciotomy is performed to prevent swelling-related complications. The wound is irrigated and injected with bupivacaine and closed in routine fashion.

We then make an inverted hockey-stick incision over the proximal tibia, centered down to the tibial tubercle. After dissecting down to the anterior compartment, we perform a fasciotomy of about 8 cm to accommodate swelling. Subperiosteal dissection is then performed around the proximal tibia. The medial soft tissues are left attached to increase blood supply and healing. During subperiosteal dissection, soft elevators are used to gently retract the lateral soft tissues along with the inferior and posterior structures. We use fluoroscopic imaging to guide the osteotomy as well as screw and plate placement. We use a 6-hole, 4.5-mm compression plate and screws for fixation. The 2 proximal screws of the plate are predrilled in place to allow for application of the plate after completion of the osteotomy. The plate is then rotated out of position on 1 screw, and the osteotomy is identified under fluoroscopy with the appropriate position distal to the second hole of the 6-hole plate.

An oscillating saw and osteotomes are used to perform the oblique osteotomy. The pre-estimated bone wedge is removed. Wedge size is adjusted, if needed. The bone wedge is morselized for bone graft. The osteotomy is then closed, correcting both varus and internal tibial torsion. Our goal is 5° valgus. After correction is obtained, the plate is placed, and the proximal screw is snugly seated. Three cortical screws are placed distally to hold the plate in place under compression mode, and a cancellous screw is placed superiorly at the proximal portion of the plate for additional fixation. The screw placed proximal to the osteotomy site is a fully threaded cortical screw with excellent compression. Correction and proper placement of hardware are verified with fluoroscopy.

The wound is irrigated and injected with bupivacaine. Bone graft is then placed at the osteotomy site. Additional bone graft is placed posteriorly between the osteotomy site and the muscle mass to stimulate additional healing. Another screw is placed obliquely from the medial side across the osteotomy site to provide additional fixation (Figure 1).

Copyright belongs to the authors

A deep drain is placed and connected to bulb suction for 24 hours after surgery. The wound is then closed in routine fashion. In 2 patients who weighed more than 250 pounds, we used an external fixator for additional stability (Figure 2).

Copyright belongs to the authors

Postoperative Care

The incisions are dressed with antibiotic ointment and 4×4-in bandages and then wrapped with sterile cotton under-cast padding. The leg is placed into a well-padded cylinder cast with the knee flexed 10°. The leg is aligned to about 5° valgus. The cast is then split on the side and spread to allow for swelling and to prevent compartment syndrome.⁵ We also use a drain hooked to bulb suction, which is removed 24 hours after surgery. Toe-touch weight-bearing with crutches is allowed immediately after surgery. The cast is removed at 6 weeks, and a hinged range-of-motion knee brace is worn for another 6 weeks. All patients are allowed to resume normal activity after 4 months. In our 2 external-fixator cases, a cast was not used, and toe-touch weight-bearing and knee motion were allowed immediately. The external fixators were removed at about 10 weeks.

Results

Mean postoperative mechanical femoral-tibial angle was 3°, and mean correction was 26° (range, 16°-43°) (Table). Lateral distal femoral angle did not show significant femoral deformity in our sample. Mean medial proximal tibial angle was 74° (range, 63°-79°). In each case, the varus deformity was primarily in the tibia. Mean tourniquet time was 88 minutes (range, 50-119 min). Our complication rate was 11% (1 knee). In our first case, in which we did not use an extra medial screw, the 4.5-mm plate fractured at the osteotomy site 2.5 months after surgery. The 250-pound patient subsequently lost 17° of correction, and valgus alignment was not achieved. Preoperative varus was 25°, and postoperative alignment was 8° varus. This plate fracture led us to use an extra medial screw for additional stability in all subsequent cases and to consider using an external fixator for patients weighing more than 250 pounds. After the first case, there were no other plate fractures. A potential problem with closing wedge osteotomy is shortening, but varus correction restores some length. Mean postoperative leg-length difference was 10 mm (range, 0-16 mm). No patient complained of leg-length difference during the postoperative follow-up.

Eight and a half months after surgery, 1 patient had hardware removed, at the family’s request. No patient experienced perioperative infection or neurovascular damage. Our overall patient population was obese—mean BMI was 38 (range, 25-48), and mean postoperative weight was 219 pounds. Three of our 8 patients were overweight (BMI, 25-30), and 5 were obese (BMI, >30). For prevention of plate failure, we recommend using an extra oblique screw in all patients and considering an external fixator for patients who weigh more than 250 pounds.

Discussion

Correction of adolescent tibia vara can be challenging because of patient obesity. The technique described here—a modification of the technique of Laurencin and colleagues⁴—is practical and reproducible in this population. The goals in performing osteotomy are to correct the deformity, restore joint alignment, preserve leg length, and prevent recurrent deformity and other complications, such as neurovascular injury, nonunion, and infection.^3,6-8 Our technique minimizes the risk for these complications. For example, the fasciotomy provides excellent decompression of the anterior and lateral compartments, minimizing neurovascular ischemia and the risk for compartment syndrome. During cast placement, splitting and spreading reduce the risk for compartment syndrome as well.⁵

Wagner3,9 demonstrated the utility of a closing wedge proximal tibial osteotomy in adults. Laurencin and colleagues4 showed this technique is effective in correcting tibia vara in a pediatric population. However, they did not specify patient weight and used a small semitubular plate for fixation, and some of their patients had infantile Blount disease. We modified the technique in 3 ways. First, we performed a complete osteotomy. Second, because our patients were adolescents and very large, we used a 6-hole, 4.5-mm compression plate and screws. Third, we used an external fixator for increased stability in patients who weighed more than 250 pounds.

The reported technique, using an oblique metaphyseal closing wedge osteotomy with internal fixation in obese patients, is practical, safe, and reliable. This technique is a useful alternative to an external fixator. We used it on 9 knees with tibia vara, and it was completely successful in 8 cases and partially successful in 1 (hardware breakage occurred). An external fixator was used to prevent hardware breakage in 2 patients who weighed more than 250 pounds. This technique is a valuable treatment option for surgical correction, especially in obese patients.

Blount disease (tibia vara) is an angular tibia deformity that includes varus, increased posterior slope, and internal rotation. This deformity was first described in 1922 by Erlacher1 in Germany. In 1937, Walter Blount2 reported on it in the United States. It is the most common cause of pathologic genu varum in adolescence and childhood.

An oblique incomplete closing wedge osteotomy of the proximal tibial metaphysis was described by Wagner³ for the treatment of unicompartmental osteoarthrosis of the knee in adults. Laurencin and colleagues⁴ applied this technique to the treatment of pediatric tibia vara with favorable results. They spared the medial cortex of the tibia in their incomplete closing wedge osteotomy technique. In each of the 9 cases we treated and describe here, we accidentally completed the tibial osteotomy when attempting the Laurencin technique. Given that the osteotomy was completed, we modified the Laurencin technique by using a 6-hole, 4.5-mm compression plate rather than a 5-hole semitubular plate, and added a large oblique screw from the medial side to compress the osteotomy site and to protect the plate from fracture. In addition, in 2 patients who weighed more than 250 pounds, we used an external fixator for additional stability. In this article, we report the outcomes of correcting adolescent tibia vara with a complete closing wedge tibial osteotomy and an oblique fibular osteotomy.

Materials and Methods

This study was approved by the Institutional Review Board at Pennsylvania State University. Between 2009 and 2012, we performed 9 complete oblique proximal tibial lateral closing wedge osteotomies on 8 patients (2 girls, 6 boys). In each case, the primary diagnosis was Blount disease. One patient also had renal dysplasia and was receiving dialysis. Mean age at time of operation was 15 years (range, 13-17 years). Mean preoperative weight was 215 pounds (range, 119-317 lb). Mean weight gain at follow-up was 4.39 pounds (range, –10 to 19 lb). Mean body mass index (BMI) was 38 (range, 25-48) (Table). All patients had varus angulation of the proximal tibia before surgery. Mean preoperative varus on standing films was 22° (range, 10°-36°). Because of the patients’ size, we used standing long-leg radiographs, on individual cassettes, for each leg.

Surgical Technique

Before surgery, we use paper cutouts to template the osteotomy wedge. We also use perioperative antibiotics and a standard time-out. For visualization of the entire leg for accurate correction, we prepare and drape the entire leg. A sterile tourniquet is used. At the midshaft of the fibula, a 4-cm incision is made, and dissection is carefully carried down to the fibula. Subperiosteal dissection is performed about the fibula, allowing adequate clearance for an oblique osteotomy. The osteotomy removes about 1 cm of fibula, which is to be used as bone graft for the tibial osteotomy. In addition, a lateral compartment fasciotomy is performed to prevent swelling-related complications. The wound is irrigated and injected with bupivacaine and closed in routine fashion.

We then make an inverted hockey-stick incision over the proximal tibia, centered down to the tibial tubercle. After dissecting down to the anterior compartment, we perform a fasciotomy of about 8 cm to accommodate swelling. Subperiosteal dissection is then performed around the proximal tibia. The medial soft tissues are left attached to increase blood supply and healing. During subperiosteal dissection, soft elevators are used to gently retract the lateral soft tissues along with the inferior and posterior structures. We use fluoroscopic imaging to guide the osteotomy as well as screw and plate placement. We use a 6-hole, 4.5-mm compression plate and screws for fixation. The 2 proximal screws of the plate are predrilled in place to allow for application of the plate after completion of the osteotomy. The plate is then rotated out of position on 1 screw, and the osteotomy is identified under fluoroscopy with the appropriate position distal to the second hole of the 6-hole plate.

An oscillating saw and osteotomes are used to perform the oblique osteotomy. The pre-estimated bone wedge is removed. Wedge size is adjusted, if needed. The bone wedge is morselized for bone graft. The osteotomy is then closed, correcting both varus and internal tibial torsion. Our goal is 5° valgus. After correction is obtained, the plate is placed, and the proximal screw is snugly seated. Three cortical screws are placed distally to hold the plate in place under compression mode, and a cancellous screw is placed superiorly at the proximal portion of the plate for additional fixation. The screw placed proximal to the osteotomy site is a fully threaded cortical screw with excellent compression. Correction and proper placement of hardware are verified with fluoroscopy.

The wound is irrigated and injected with bupivacaine. Bone graft is then placed at the osteotomy site. Additional bone graft is placed posteriorly between the osteotomy site and the muscle mass to stimulate additional healing. Another screw is placed obliquely from the medial side across the osteotomy site to provide additional fixation (Figure 1).

Copyright belongs to the authors

A deep drain is placed and connected to bulb suction for 24 hours after surgery. The wound is then closed in routine fashion. In 2 patients who weighed more than 250 pounds, we used an external fixator for additional stability (Figure 2).

Copyright belongs to the authors

Postoperative Care

The incisions are dressed with antibiotic ointment and 4×4-in bandages and then wrapped with sterile cotton under-cast padding. The leg is placed into a well-padded cylinder cast with the knee flexed 10°. The leg is aligned to about 5° valgus. The cast is then split on the side and spread to allow for swelling and to prevent compartment syndrome.⁵ We also use a drain hooked to bulb suction, which is removed 24 hours after surgery. Toe-touch weight-bearing with crutches is allowed immediately after surgery. The cast is removed at 6 weeks, and a hinged range-of-motion knee brace is worn for another 6 weeks. All patients are allowed to resume normal activity after 4 months. In our 2 external-fixator cases, a cast was not used, and toe-touch weight-bearing and knee motion were allowed immediately. The external fixators were removed at about 10 weeks.

Results

Mean postoperative mechanical femoral-tibial angle was 3°, and mean correction was 26° (range, 16°-43°) (Table). Lateral distal femoral angle did not show significant femoral deformity in our sample. Mean medial proximal tibial angle was 74° (range, 63°-79°). In each case, the varus deformity was primarily in the tibia. Mean tourniquet time was 88 minutes (range, 50-119 min). Our complication rate was 11% (1 knee). In our first case, in which we did not use an extra medial screw, the 4.5-mm plate fractured at the osteotomy site 2.5 months after surgery. The 250-pound patient subsequently lost 17° of correction, and valgus alignment was not achieved. Preoperative varus was 25°, and postoperative alignment was 8° varus. This plate fracture led us to use an extra medial screw for additional stability in all subsequent cases and to consider using an external fixator for patients weighing more than 250 pounds. After the first case, there were no other plate fractures. A potential problem with closing wedge osteotomy is shortening, but varus correction restores some length. Mean postoperative leg-length difference was 10 mm (range, 0-16 mm). No patient complained of leg-length difference during the postoperative follow-up.

Eight and a half months after surgery, 1 patient had hardware removed, at the family’s request. No patient experienced perioperative infection or neurovascular damage. Our overall patient population was obese—mean BMI was 38 (range, 25-48), and mean postoperative weight was 219 pounds. Three of our 8 patients were overweight (BMI, 25-30), and 5 were obese (BMI, >30). For prevention of plate failure, we recommend using an extra oblique screw in all patients and considering an external fixator for patients who weigh more than 250 pounds.

Discussion

Correction of adolescent tibia vara can be challenging because of patient obesity. The technique described here—a modification of the technique of Laurencin and colleagues⁴—is practical and reproducible in this population. The goals in performing osteotomy are to correct the deformity, restore joint alignment, preserve leg length, and prevent recurrent deformity and other complications, such as neurovascular injury, nonunion, and infection.^3,6-8 Our technique minimizes the risk for these complications. For example, the fasciotomy provides excellent decompression of the anterior and lateral compartments, minimizing neurovascular ischemia and the risk for compartment syndrome. During cast placement, splitting and spreading reduce the risk for compartment syndrome as well.⁵

Wagner3,9 demonstrated the utility of a closing wedge proximal tibial osteotomy in adults. Laurencin and colleagues4 showed this technique is effective in correcting tibia vara in a pediatric population. However, they did not specify patient weight and used a small semitubular plate for fixation, and some of their patients had infantile Blount disease. We modified the technique in 3 ways. First, we performed a complete osteotomy. Second, because our patients were adolescents and very large, we used a 6-hole, 4.5-mm compression plate and screws. Third, we used an external fixator for increased stability in patients who weighed more than 250 pounds.

The reported technique, using an oblique metaphyseal closing wedge osteotomy with internal fixation in obese patients, is practical, safe, and reliable. This technique is a useful alternative to an external fixator. We used it on 9 knees with tibia vara, and it was completely successful in 8 cases and partially successful in 1 (hardware breakage occurred). An external fixator was used to prevent hardware breakage in 2 patients who weighed more than 250 pounds. This technique is a valuable treatment option for surgical correction, especially in obese patients.

Blount disease (tibia vara) is an angular tibia deformity that includes varus, increased posterior slope, and internal rotation. This deformity was first described in 1922 by Erlacher1 in Germany. In 1937, Walter Blount2 reported on it in the United States. It is the most common cause of pathologic genu varum in adolescence and childhood.

An oblique incomplete closing wedge osteotomy of the proximal tibial metaphysis was described by Wagner³ for the treatment of unicompartmental osteoarthrosis of the knee in adults. Laurencin and colleagues⁴ applied this technique to the treatment of pediatric tibia vara with favorable results. They spared the medial cortex of the tibia in their incomplete closing wedge osteotomy technique. In each of the 9 cases we treated and describe here, we accidentally completed the tibial osteotomy when attempting the Laurencin technique. Given that the osteotomy was completed, we modified the Laurencin technique by using a 6-hole, 4.5-mm compression plate rather than a 5-hole semitubular plate, and added a large oblique screw from the medial side to compress the osteotomy site and to protect the plate from fracture. In addition, in 2 patients who weighed more than 250 pounds, we used an external fixator for additional stability. In this article, we report the outcomes of correcting adolescent tibia vara with a complete closing wedge tibial osteotomy and an oblique fibular osteotomy.

Materials and Methods

This study was approved by the Institutional Review Board at Pennsylvania State University. Between 2009 and 2012, we performed 9 complete oblique proximal tibial lateral closing wedge osteotomies on 8 patients (2 girls, 6 boys). In each case, the primary diagnosis was Blount disease. One patient also had renal dysplasia and was receiving dialysis. Mean age at time of operation was 15 years (range, 13-17 years). Mean preoperative weight was 215 pounds (range, 119-317 lb). Mean weight gain at follow-up was 4.39 pounds (range, –10 to 19 lb). Mean body mass index (BMI) was 38 (range, 25-48) (Table). All patients had varus angulation of the proximal tibia before surgery. Mean preoperative varus on standing films was 22° (range, 10°-36°). Because of the patients’ size, we used standing long-leg radiographs, on individual cassettes, for each leg.

Surgical Technique

Before surgery, we use paper cutouts to template the osteotomy wedge. We also use perioperative antibiotics and a standard time-out. For visualization of the entire leg for accurate correction, we prepare and drape the entire leg. A sterile tourniquet is used. At the midshaft of the fibula, a 4-cm incision is made, and dissection is carefully carried down to the fibula. Subperiosteal dissection is performed about the fibula, allowing adequate clearance for an oblique osteotomy. The osteotomy removes about 1 cm of fibula, which is to be used as bone graft for the tibial osteotomy. In addition, a lateral compartment fasciotomy is performed to prevent swelling-related complications. The wound is irrigated and injected with bupivacaine and closed in routine fashion.

We then make an inverted hockey-stick incision over the proximal tibia, centered down to the tibial tubercle. After dissecting down to the anterior compartment, we perform a fasciotomy of about 8 cm to accommodate swelling. Subperiosteal dissection is then performed around the proximal tibia. The medial soft tissues are left attached to increase blood supply and healing. During subperiosteal dissection, soft elevators are used to gently retract the lateral soft tissues along with the inferior and posterior structures. We use fluoroscopic imaging to guide the osteotomy as well as screw and plate placement. We use a 6-hole, 4.5-mm compression plate and screws for fixation. The 2 proximal screws of the plate are predrilled in place to allow for application of the plate after completion of the osteotomy. The plate is then rotated out of position on 1 screw, and the osteotomy is identified under fluoroscopy with the appropriate position distal to the second hole of the 6-hole plate.

An oscillating saw and osteotomes are used to perform the oblique osteotomy. The pre-estimated bone wedge is removed. Wedge size is adjusted, if needed. The bone wedge is morselized for bone graft. The osteotomy is then closed, correcting both varus and internal tibial torsion. Our goal is 5° valgus. After correction is obtained, the plate is placed, and the proximal screw is snugly seated. Three cortical screws are placed distally to hold the plate in place under compression mode, and a cancellous screw is placed superiorly at the proximal portion of the plate for additional fixation. The screw placed proximal to the osteotomy site is a fully threaded cortical screw with excellent compression. Correction and proper placement of hardware are verified with fluoroscopy.

The wound is irrigated and injected with bupivacaine. Bone graft is then placed at the osteotomy site. Additional bone graft is placed posteriorly between the osteotomy site and the muscle mass to stimulate additional healing. Another screw is placed obliquely from the medial side across the osteotomy site to provide additional fixation (Figure 1).

Copyright belongs to the authors

A deep drain is placed and connected to bulb suction for 24 hours after surgery. The wound is then closed in routine fashion. In 2 patients who weighed more than 250 pounds, we used an external fixator for additional stability (Figure 2).

Copyright belongs to the authors

Postoperative Care

The incisions are dressed with antibiotic ointment and 4×4-in bandages and then wrapped with sterile cotton under-cast padding. The leg is placed into a well-padded cylinder cast with the knee flexed 10°. The leg is aligned to about 5° valgus. The cast is then split on the side and spread to allow for swelling and to prevent compartment syndrome.⁵ We also use a drain hooked to bulb suction, which is removed 24 hours after surgery. Toe-touch weight-bearing with crutches is allowed immediately after surgery. The cast is removed at 6 weeks, and a hinged range-of-motion knee brace is worn for another 6 weeks. All patients are allowed to resume normal activity after 4 months. In our 2 external-fixator cases, a cast was not used, and toe-touch weight-bearing and knee motion were allowed immediately. The external fixators were removed at about 10 weeks.

Results

Mean postoperative mechanical femoral-tibial angle was 3°, and mean correction was 26° (range, 16°-43°) (Table). Lateral distal femoral angle did not show significant femoral deformity in our sample. Mean medial proximal tibial angle was 74° (range, 63°-79°). In each case, the varus deformity was primarily in the tibia. Mean tourniquet time was 88 minutes (range, 50-119 min). Our complication rate was 11% (1 knee). In our first case, in which we did not use an extra medial screw, the 4.5-mm plate fractured at the osteotomy site 2.5 months after surgery. The 250-pound patient subsequently lost 17° of correction, and valgus alignment was not achieved. Preoperative varus was 25°, and postoperative alignment was 8° varus. This plate fracture led us to use an extra medial screw for additional stability in all subsequent cases and to consider using an external fixator for patients weighing more than 250 pounds. After the first case, there were no other plate fractures. A potential problem with closing wedge osteotomy is shortening, but varus correction restores some length. Mean postoperative leg-length difference was 10 mm (range, 0-16 mm). No patient complained of leg-length difference during the postoperative follow-up.

Eight and a half months after surgery, 1 patient had hardware removed, at the family’s request. No patient experienced perioperative infection or neurovascular damage. Our overall patient population was obese—mean BMI was 38 (range, 25-48), and mean postoperative weight was 219 pounds. Three of our 8 patients were overweight (BMI, 25-30), and 5 were obese (BMI, >30). For prevention of plate failure, we recommend using an extra oblique screw in all patients and considering an external fixator for patients who weigh more than 250 pounds.

Discussion

Correction of adolescent tibia vara can be challenging because of patient obesity. The technique described here—a modification of the technique of Laurencin and colleagues⁴—is practical and reproducible in this population. The goals in performing osteotomy are to correct the deformity, restore joint alignment, preserve leg length, and prevent recurrent deformity and other complications, such as neurovascular injury, nonunion, and infection.^3,6-8 Our technique minimizes the risk for these complications. For example, the fasciotomy provides excellent decompression of the anterior and lateral compartments, minimizing neurovascular ischemia and the risk for compartment syndrome. During cast placement, splitting and spreading reduce the risk for compartment syndrome as well.⁵

Wagner3,9 demonstrated the utility of a closing wedge proximal tibial osteotomy in adults. Laurencin and colleagues4 showed this technique is effective in correcting tibia vara in a pediatric population. However, they did not specify patient weight and used a small semitubular plate for fixation, and some of their patients had infantile Blount disease. We modified the technique in 3 ways. First, we performed a complete osteotomy. Second, because our patients were adolescents and very large, we used a 6-hole, 4.5-mm compression plate and screws. Third, we used an external fixator for increased stability in patients who weighed more than 250 pounds.

The reported technique, using an oblique metaphyseal closing wedge osteotomy with internal fixation in obese patients, is practical, safe, and reliable. This technique is a useful alternative to an external fixator. We used it on 9 knees with tibia vara, and it was completely successful in 8 cases and partially successful in 1 (hardware breakage occurred). An external fixator was used to prevent hardware breakage in 2 patients who weighed more than 250 pounds. This technique is a valuable treatment option for surgical correction, especially in obese patients.

Orthopedic surgery is going through a time of remarkable change. Health care reform, heightened public scrutiny, shifting population demographics, increased reliance on the Internet for information, ongoing metamorphosis of our profession into a business, and lack of consistent high-quality clinical evidence have created a new frontier of challenges and opportunities. At heart are the needs to deliver high-quality education that is in line with new technological media, to reclaim our ability to guide musculoskeletal care at the policymaking level, to fortify our long-held tradition of ethical responsibility, to invest in research and the training of physician-scientists, to maintain unity among the different subspecialties, and to increase female and minority representation. Never before has understanding and applying the key tenets of our philosophy as orthopedic surgeons been more crucial.

The changing landscape of orthopedic practice has been an unsettling topic in many of the American Academy of Orthopaedic Surgeons (AAOS) presidential addresses in recent years.^1-11 What are the challenges and what can we learn moving forward? In this article, we seek to answer these questions by drawing insights from the combined experience and wisdom of past AAOS presidents since the turn of the 21st century.

Education

Education is the cornerstone of providing quality musculoskeletal care¹² and staying up to date with technological advances.¹³ The modes of education delivery, however, have changed. No longer is orthopedic education confined to tangible textbooks and journal articles, nor is it limited to those of us in the profession. Instead, orthopedic education has shifted toward online learning¹⁴ and is available to patients and nonorthopedic providers.¹² With more patients gaining access to rapidly growing online resources, a unique challenge has arisen: an abundance of data with variable quality of evidence influencing the decision-making process. This has created what Richard Kyle¹⁵ described as the “trap of the new technology war,” where patient misinformation and direct-to-consumer marketing can lead to dangerous musculoskeletal care delivery, including unrealistic patient expectations.³ To compound the problem, our ability to provide orthopedic education in formats compatible with the new learning mediums has not been up to the demand, with issues of cost, accessibility, and efficacy plaguing the current process.^3,5 Also, we have yet to unlock the benefits of surgical simulation, which has the potential to provide more effective training at no risk to the patient.^4,13 By adapting to the new learning formats, we can provide numerous new opportunities for keeping up to date on evolving practice management principles, which, with added accessibility, will be used more often by orthopedic surgeons and the public.¹³ 

Research

Research is vital for quality improvement and the continuation of excellence.⁵ It is only with research that we can provide groundbreaking advances and measure the outcomes of our interventions.² Unfortunately, orthopedic research funding continues to be disproportionately low, especially given that musculoskeletal ailments are the leading cause of both physician visits and chronic impairment in the United States.² For example, the National Institute of Arthritis and Musculoskeletal and Skin Diseases receives only 10% of what our country spends on cancer research and 15% of what is spent on heart- and lung-disease research.² To compound the problem of limited funding, the number of physician-scientists has been dropping at an alarming rate.² As a result, we must not only refocus our research efforts so that they are efficient and effective, but we must also invest in the training of orthopedic physician-scientists to ensure a continuous stream of groundbreaking discoveries. We owe it to our patients to provide them with proven, effective, and high-quality care.

Industry Relationships

Local and national attention will continue to focus on our relationships with industry. The challenge is twofold: mitigating the negative portrayal of industry relationships and navigating the changes applied to industry funding for research and education.⁹ Our collaboration with industry is important for the development and advancement of orthopedics,¹⁵ but it must be guided by the professional and ethical guidelines established by the AAOS, ensuring that the best interest of patients remains a top priority.^8,15 We must maintain the public’s trust by using every opportunity to convey our lone goal in collaborating with industry, ie, improving patient care.⁹ According to James Beaty,⁷ any relationship with industry should be “so ethical that it could be printed on the front page of the newspaper and we could face our neighbors with our heads held high.”

Gender and Minority Representation

The racial and ethnic makeup of the United States is undergoing a rapid change. Over the next 4 decades, the white population is projected to become the minority, while women will continue to outnumber men.¹⁶ Despite the rapidly changing demographics of the United States, health care disparities persist. As of 2011, minorities and women made up only 22.55% and 14.52%, respectively, of all orthopedic surgery residents.¹⁷ This limited diversity in orthopedic training programs is alarming and may lead to suboptimal physician–patient relationships, because patients tend to be more comfortable with and respond better to the care provided by physicians of similar background.³ In addition, if we do not integrate women into orthopedics, the number of female medical students applying to orthopedic residency programs might decline.³

Equating excellent medical care with diversity and cultural competence requires that we bridge the gap that has prevented patients from obtaining high-quality care.⁸ To achieve this goal, we need to continue recruiting orthopedic surgeons from all segments of our population. Ultimately, health care disparities can be effectively reduced through the delivery of culturally competent care.⁸

Physician–Patient Relationship

Medical liability has resulted in the development of damaging attitudes among physicians, with many viewing patients as potential adversaries and even avoiding high-risk procedures altogether.⁶ This deterioration of the physician–patient relationship has been another troubling consequence of managed care that emphasizes quantity and speed.¹ As a result, we are perceived by the public as impersonal, poor listeners, and difficult to see on short notice.¹

The poor perception of orthopedic surgeons by the general public is not acceptable for a field that places such a high value on excellence. Patient-centered care is at the core of quality improvement, and improving patient relationships starts and ends with us and with each patient we treat.⁶ In a health care environment in which the average orthopedic surgeon cares for thousands of patients each year, we must make certain to use each opportunity to engage our patients and enhance our relationships with them.⁶ The basic necessities of patient-centered care include empowerment of the patient through education, better communication, and transparency; providing accurate and evidence-based information; and cooperation among physicians.^3,6 The benefits of improving personal relationships with patients are multifold and could have lasting positive effects: increased physician and patient satisfaction, better patient compliance, greater practice efficiency, and fewer malpractice lawsuits.¹ We can also benefit from mobilizing a greater constituency to advocate alongside us.⁶

Unity

Despite accounting for less than 3% of all physicians, orthopedic surgeons have assumed an influential voice in the field of medicine.¹³ This is attributed not only to the success of our interventions but, more importantly, to the fact that we have “stuck together.”¹³ The concept of “sticking together” may seem a cliché and facile but will certainly be a pressing need as we move ahead. We draw strength from the breadth and diversity of our subspecialties, but this strength may become a weakness if we do not join in promoting the betterment of our profession as a whole.¹⁴ To avoid duplications and bring synergy to all our efforts, we should continue to develop new partnerships in our specialty societies⁶ and speak with one voice to our patients and to the public.¹⁵ Joshua Jacobs¹¹ reminds us of the warning Benjamin Franklin imparted to the signers of the Declaration of Independence, “We must hang together, or most assuredly, we will all hang separately.” To ensure the continued strength of the house of orthopedics, we must live by this tenet.

Advocacy

The federal government has become increasingly involved in regulating the practice of medicine.⁹ Orthopedic surgery has been hit especially hard, because the cost of implants and continued innovation has fueled the belief that our profession is a major contributor to unsustainable health care costs.¹¹ We now face multiple legislative regulations related to physician reimbursement, ownership, self-referral, medical liability, and mandates of the Affordable Care Act.⁹ As a result, there has been a decreasing role for orthopedic surgeons as independent practitioners, with more orthopedists forgoing physician-owned practices for large hospital corporations. We are also in increasing competition for limited resources.¹⁰ This is compounded by the fact that those regulating health care, paying for health care, and allocating research funding fail to comprehend the high societal needs for treatment of musculoskeletal diseases and injuries,⁶ which will only increase in the coming decades.¹⁴

The aforementioned challenges make our involvement at all levels of the political process more necessary than ever before.^5,9 E. Anthony Rankin⁸ reminds us, “As physicians, we cannot in good conscience allow our patients’ access to quality orthopedic care to be determined solely by the government, the insurance companies, the trial lawyers, or others…. Either we will have a voice in defining the future of health care, or it will be defined by others for us.” Our advocacy approach, however, should be very careful. Joshua Jacobs¹¹ cautions that “we will be most effective if our advocacy message is presented as a potential solution to the current health care crisis, not just as a demand for fair reimbursement.” Instead, we can achieve this goal with what Richard Gelberman² summarized as “doing what we do best: accumulating knowledge, positioning ourselves as the authorities that we are, and using what we learn to advocate for better patient care and research.”

Value Medicine

Orthopedic surgeons are now expected to provide not just high-quality care but low-cost care. In line with the emerging emphasis on value, sharp focus has been placed on the assessment of physician performance and treatment outcomes as quality-of-care measures.⁶ But how have we measured the quality of the care we provide? We have not, or, at least, we have not had valid or reliable means of doing so.⁶ Gone are the days of telling the world of the excellence of our profession in the treatment of musculoskeletal disease. We now must prove to our patients, the government, and payers that what we do works.^12,13 If we fail to communicate the cost effectiveness of our interventions, our new knowledge and technologies will not be accepted or funded.¹⁰ We should, however, not be discouraged by the new “value equation,” but use it as an incentive to provide evidence-based care and to improve the efficiency of resource utilization.¹⁴ Today, we are urged to be leaders in quality improvement, both in our individual orthopedic practices and as a profession.^10,12,13

Conclusion

Meeting increasingly higher demands for musculoskeletal care in an evolving medical landscape will bring a new set of challenges that will be more frequent and more intense than those in the past.¹⁴ Today, we are tasked with providing fiscally efficient, culturally competent, high-quality, evidence-based, and compassionate care. We are also tasked with reclaiming our ability to shape the future of our profession at the policymaking level. In doing so, the need for unity, advocacy, commitment to education and research, women and minority representation, and open communication with the public has never been more relevant. As we continue to advance as a profession, we must resist the temptation to look back in defiance of change but move forward, confident in our ability to evolve. ◾

Orthopedic surgery is going through a time of remarkable change. Health care reform, heightened public scrutiny, shifting population demographics, increased reliance on the Internet for information, ongoing metamorphosis of our profession into a business, and lack of consistent high-quality clinical evidence have created a new frontier of challenges and opportunities. At heart are the needs to deliver high-quality education that is in line with new technological media, to reclaim our ability to guide musculoskeletal care at the policymaking level, to fortify our long-held tradition of ethical responsibility, to invest in research and the training of physician-scientists, to maintain unity among the different subspecialties, and to increase female and minority representation. Never before has understanding and applying the key tenets of our philosophy as orthopedic surgeons been more crucial.

The changing landscape of orthopedic practice has been an unsettling topic in many of the American Academy of Orthopaedic Surgeons (AAOS) presidential addresses in recent years.^1-11 What are the challenges and what can we learn moving forward? In this article, we seek to answer these questions by drawing insights from the combined experience and wisdom of past AAOS presidents since the turn of the 21st century.

Education

Education is the cornerstone of providing quality musculoskeletal care¹² and staying up to date with technological advances.¹³ The modes of education delivery, however, have changed. No longer is orthopedic education confined to tangible textbooks and journal articles, nor is it limited to those of us in the profession. Instead, orthopedic education has shifted toward online learning¹⁴ and is available to patients and nonorthopedic providers.¹² With more patients gaining access to rapidly growing online resources, a unique challenge has arisen: an abundance of data with variable quality of evidence influencing the decision-making process. This has created what Richard Kyle¹⁵ described as the “trap of the new technology war,” where patient misinformation and direct-to-consumer marketing can lead to dangerous musculoskeletal care delivery, including unrealistic patient expectations.³ To compound the problem, our ability to provide orthopedic education in formats compatible with the new learning mediums has not been up to the demand, with issues of cost, accessibility, and efficacy plaguing the current process.^3,5 Also, we have yet to unlock the benefits of surgical simulation, which has the potential to provide more effective training at no risk to the patient.^4,13 By adapting to the new learning formats, we can provide numerous new opportunities for keeping up to date on evolving practice management principles, which, with added accessibility, will be used more often by orthopedic surgeons and the public.¹³ 

Research

Research is vital for quality improvement and the continuation of excellence.⁵ It is only with research that we can provide groundbreaking advances and measure the outcomes of our interventions.² Unfortunately, orthopedic research funding continues to be disproportionately low, especially given that musculoskeletal ailments are the leading cause of both physician visits and chronic impairment in the United States.² For example, the National Institute of Arthritis and Musculoskeletal and Skin Diseases receives only 10% of what our country spends on cancer research and 15% of what is spent on heart- and lung-disease research.² To compound the problem of limited funding, the number of physician-scientists has been dropping at an alarming rate.² As a result, we must not only refocus our research efforts so that they are efficient and effective, but we must also invest in the training of orthopedic physician-scientists to ensure a continuous stream of groundbreaking discoveries. We owe it to our patients to provide them with proven, effective, and high-quality care.

Industry Relationships

Local and national attention will continue to focus on our relationships with industry. The challenge is twofold: mitigating the negative portrayal of industry relationships and navigating the changes applied to industry funding for research and education.⁹ Our collaboration with industry is important for the development and advancement of orthopedics,¹⁵ but it must be guided by the professional and ethical guidelines established by the AAOS, ensuring that the best interest of patients remains a top priority.^8,15 We must maintain the public’s trust by using every opportunity to convey our lone goal in collaborating with industry, ie, improving patient care.⁹ According to James Beaty,⁷ any relationship with industry should be “so ethical that it could be printed on the front page of the newspaper and we could face our neighbors with our heads held high.”

Gender and Minority Representation

The racial and ethnic makeup of the United States is undergoing a rapid change. Over the next 4 decades, the white population is projected to become the minority, while women will continue to outnumber men.¹⁶ Despite the rapidly changing demographics of the United States, health care disparities persist. As of 2011, minorities and women made up only 22.55% and 14.52%, respectively, of all orthopedic surgery residents.¹⁷ This limited diversity in orthopedic training programs is alarming and may lead to suboptimal physician–patient relationships, because patients tend to be more comfortable with and respond better to the care provided by physicians of similar background.³ In addition, if we do not integrate women into orthopedics, the number of female medical students applying to orthopedic residency programs might decline.³

Equating excellent medical care with diversity and cultural competence requires that we bridge the gap that has prevented patients from obtaining high-quality care.⁸ To achieve this goal, we need to continue recruiting orthopedic surgeons from all segments of our population. Ultimately, health care disparities can be effectively reduced through the delivery of culturally competent care.⁸

Physician–Patient Relationship

Medical liability has resulted in the development of damaging attitudes among physicians, with many viewing patients as potential adversaries and even avoiding high-risk procedures altogether.⁶ This deterioration of the physician–patient relationship has been another troubling consequence of managed care that emphasizes quantity and speed.¹ As a result, we are perceived by the public as impersonal, poor listeners, and difficult to see on short notice.¹

The poor perception of orthopedic surgeons by the general public is not acceptable for a field that places such a high value on excellence. Patient-centered care is at the core of quality improvement, and improving patient relationships starts and ends with us and with each patient we treat.⁶ In a health care environment in which the average orthopedic surgeon cares for thousands of patients each year, we must make certain to use each opportunity to engage our patients and enhance our relationships with them.⁶ The basic necessities of patient-centered care include empowerment of the patient through education, better communication, and transparency; providing accurate and evidence-based information; and cooperation among physicians.^3,6 The benefits of improving personal relationships with patients are multifold and could have lasting positive effects: increased physician and patient satisfaction, better patient compliance, greater practice efficiency, and fewer malpractice lawsuits.¹ We can also benefit from mobilizing a greater constituency to advocate alongside us.⁶

Unity

Despite accounting for less than 3% of all physicians, orthopedic surgeons have assumed an influential voice in the field of medicine.¹³ This is attributed not only to the success of our interventions but, more importantly, to the fact that we have “stuck together.”¹³ The concept of “sticking together” may seem a cliché and facile but will certainly be a pressing need as we move ahead. We draw strength from the breadth and diversity of our subspecialties, but this strength may become a weakness if we do not join in promoting the betterment of our profession as a whole.¹⁴ To avoid duplications and bring synergy to all our efforts, we should continue to develop new partnerships in our specialty societies⁶ and speak with one voice to our patients and to the public.¹⁵ Joshua Jacobs¹¹ reminds us of the warning Benjamin Franklin imparted to the signers of the Declaration of Independence, “We must hang together, or most assuredly, we will all hang separately.” To ensure the continued strength of the house of orthopedics, we must live by this tenet.

Advocacy

The federal government has become increasingly involved in regulating the practice of medicine.⁹ Orthopedic surgery has been hit especially hard, because the cost of implants and continued innovation has fueled the belief that our profession is a major contributor to unsustainable health care costs.¹¹ We now face multiple legislative regulations related to physician reimbursement, ownership, self-referral, medical liability, and mandates of the Affordable Care Act.⁹ As a result, there has been a decreasing role for orthopedic surgeons as independent practitioners, with more orthopedists forgoing physician-owned practices for large hospital corporations. We are also in increasing competition for limited resources.¹⁰ This is compounded by the fact that those regulating health care, paying for health care, and allocating research funding fail to comprehend the high societal needs for treatment of musculoskeletal diseases and injuries,⁶ which will only increase in the coming decades.¹⁴

The aforementioned challenges make our involvement at all levels of the political process more necessary than ever before.^5,9 E. Anthony Rankin⁸ reminds us, “As physicians, we cannot in good conscience allow our patients’ access to quality orthopedic care to be determined solely by the government, the insurance companies, the trial lawyers, or others…. Either we will have a voice in defining the future of health care, or it will be defined by others for us.” Our advocacy approach, however, should be very careful. Joshua Jacobs¹¹ cautions that “we will be most effective if our advocacy message is presented as a potential solution to the current health care crisis, not just as a demand for fair reimbursement.” Instead, we can achieve this goal with what Richard Gelberman² summarized as “doing what we do best: accumulating knowledge, positioning ourselves as the authorities that we are, and using what we learn to advocate for better patient care and research.”

Value Medicine

Orthopedic surgeons are now expected to provide not just high-quality care but low-cost care. In line with the emerging emphasis on value, sharp focus has been placed on the assessment of physician performance and treatment outcomes as quality-of-care measures.⁶ But how have we measured the quality of the care we provide? We have not, or, at least, we have not had valid or reliable means of doing so.⁶ Gone are the days of telling the world of the excellence of our profession in the treatment of musculoskeletal disease. We now must prove to our patients, the government, and payers that what we do works.^12,13 If we fail to communicate the cost effectiveness of our interventions, our new knowledge and technologies will not be accepted or funded.¹⁰ We should, however, not be discouraged by the new “value equation,” but use it as an incentive to provide evidence-based care and to improve the efficiency of resource utilization.¹⁴ Today, we are urged to be leaders in quality improvement, both in our individual orthopedic practices and as a profession.^10,12,13

Conclusion

Meeting increasingly higher demands for musculoskeletal care in an evolving medical landscape will bring a new set of challenges that will be more frequent and more intense than those in the past.¹⁴ Today, we are tasked with providing fiscally efficient, culturally competent, high-quality, evidence-based, and compassionate care. We are also tasked with reclaiming our ability to shape the future of our profession at the policymaking level. In doing so, the need for unity, advocacy, commitment to education and research, women and minority representation, and open communication with the public has never been more relevant. As we continue to advance as a profession, we must resist the temptation to look back in defiance of change but move forward, confident in our ability to evolve. ◾

Orthopedic surgery is going through a time of remarkable change. Health care reform, heightened public scrutiny, shifting population demographics, increased reliance on the Internet for information, ongoing metamorphosis of our profession into a business, and lack of consistent high-quality clinical evidence have created a new frontier of challenges and opportunities. At heart are the needs to deliver high-quality education that is in line with new technological media, to reclaim our ability to guide musculoskeletal care at the policymaking level, to fortify our long-held tradition of ethical responsibility, to invest in research and the training of physician-scientists, to maintain unity among the different subspecialties, and to increase female and minority representation. Never before has understanding and applying the key tenets of our philosophy as orthopedic surgeons been more crucial.

The changing landscape of orthopedic practice has been an unsettling topic in many of the American Academy of Orthopaedic Surgeons (AAOS) presidential addresses in recent years.^1-11 What are the challenges and what can we learn moving forward? In this article, we seek to answer these questions by drawing insights from the combined experience and wisdom of past AAOS presidents since the turn of the 21st century.

Education

Education is the cornerstone of providing quality musculoskeletal care¹² and staying up to date with technological advances.¹³ The modes of education delivery, however, have changed. No longer is orthopedic education confined to tangible textbooks and journal articles, nor is it limited to those of us in the profession. Instead, orthopedic education has shifted toward online learning¹⁴ and is available to patients and nonorthopedic providers.¹² With more patients gaining access to rapidly growing online resources, a unique challenge has arisen: an abundance of data with variable quality of evidence influencing the decision-making process. This has created what Richard Kyle¹⁵ described as the “trap of the new technology war,” where patient misinformation and direct-to-consumer marketing can lead to dangerous musculoskeletal care delivery, including unrealistic patient expectations.³ To compound the problem, our ability to provide orthopedic education in formats compatible with the new learning mediums has not been up to the demand, with issues of cost, accessibility, and efficacy plaguing the current process.^3,5 Also, we have yet to unlock the benefits of surgical simulation, which has the potential to provide more effective training at no risk to the patient.^4,13 By adapting to the new learning formats, we can provide numerous new opportunities for keeping up to date on evolving practice management principles, which, with added accessibility, will be used more often by orthopedic surgeons and the public.¹³ 

Research

Research is vital for quality improvement and the continuation of excellence.⁵ It is only with research that we can provide groundbreaking advances and measure the outcomes of our interventions.² Unfortunately, orthopedic research funding continues to be disproportionately low, especially given that musculoskeletal ailments are the leading cause of both physician visits and chronic impairment in the United States.² For example, the National Institute of Arthritis and Musculoskeletal and Skin Diseases receives only 10% of what our country spends on cancer research and 15% of what is spent on heart- and lung-disease research.² To compound the problem of limited funding, the number of physician-scientists has been dropping at an alarming rate.² As a result, we must not only refocus our research efforts so that they are efficient and effective, but we must also invest in the training of orthopedic physician-scientists to ensure a continuous stream of groundbreaking discoveries. We owe it to our patients to provide them with proven, effective, and high-quality care.

Industry Relationships

Local and national attention will continue to focus on our relationships with industry. The challenge is twofold: mitigating the negative portrayal of industry relationships and navigating the changes applied to industry funding for research and education.⁹ Our collaboration with industry is important for the development and advancement of orthopedics,¹⁵ but it must be guided by the professional and ethical guidelines established by the AAOS, ensuring that the best interest of patients remains a top priority.^8,15 We must maintain the public’s trust by using every opportunity to convey our lone goal in collaborating with industry, ie, improving patient care.⁹ According to James Beaty,⁷ any relationship with industry should be “so ethical that it could be printed on the front page of the newspaper and we could face our neighbors with our heads held high.”

Gender and Minority Representation

The racial and ethnic makeup of the United States is undergoing a rapid change. Over the next 4 decades, the white population is projected to become the minority, while women will continue to outnumber men.¹⁶ Despite the rapidly changing demographics of the United States, health care disparities persist. As of 2011, minorities and women made up only 22.55% and 14.52%, respectively, of all orthopedic surgery residents.¹⁷ This limited diversity in orthopedic training programs is alarming and may lead to suboptimal physician–patient relationships, because patients tend to be more comfortable with and respond better to the care provided by physicians of similar background.³ In addition, if we do not integrate women into orthopedics, the number of female medical students applying to orthopedic residency programs might decline.³

Equating excellent medical care with diversity and cultural competence requires that we bridge the gap that has prevented patients from obtaining high-quality care.⁸ To achieve this goal, we need to continue recruiting orthopedic surgeons from all segments of our population. Ultimately, health care disparities can be effectively reduced through the delivery of culturally competent care.⁸

Physician–Patient Relationship

Medical liability has resulted in the development of damaging attitudes among physicians, with many viewing patients as potential adversaries and even avoiding high-risk procedures altogether.⁶ This deterioration of the physician–patient relationship has been another troubling consequence of managed care that emphasizes quantity and speed.¹ As a result, we are perceived by the public as impersonal, poor listeners, and difficult to see on short notice.¹

The poor perception of orthopedic surgeons by the general public is not acceptable for a field that places such a high value on excellence. Patient-centered care is at the core of quality improvement, and improving patient relationships starts and ends with us and with each patient we treat.⁶ In a health care environment in which the average orthopedic surgeon cares for thousands of patients each year, we must make certain to use each opportunity to engage our patients and enhance our relationships with them.⁶ The basic necessities of patient-centered care include empowerment of the patient through education, better communication, and transparency; providing accurate and evidence-based information; and cooperation among physicians.^3,6 The benefits of improving personal relationships with patients are multifold and could have lasting positive effects: increased physician and patient satisfaction, better patient compliance, greater practice efficiency, and fewer malpractice lawsuits.¹ We can also benefit from mobilizing a greater constituency to advocate alongside us.⁶

Unity

Despite accounting for less than 3% of all physicians, orthopedic surgeons have assumed an influential voice in the field of medicine.¹³ This is attributed not only to the success of our interventions but, more importantly, to the fact that we have “stuck together.”¹³ The concept of “sticking together” may seem a cliché and facile but will certainly be a pressing need as we move ahead. We draw strength from the breadth and diversity of our subspecialties, but this strength may become a weakness if we do not join in promoting the betterment of our profession as a whole.¹⁴ To avoid duplications and bring synergy to all our efforts, we should continue to develop new partnerships in our specialty societies⁶ and speak with one voice to our patients and to the public.¹⁵ Joshua Jacobs¹¹ reminds us of the warning Benjamin Franklin imparted to the signers of the Declaration of Independence, “We must hang together, or most assuredly, we will all hang separately.” To ensure the continued strength of the house of orthopedics, we must live by this tenet.

Advocacy

The federal government has become increasingly involved in regulating the practice of medicine.⁹ Orthopedic surgery has been hit especially hard, because the cost of implants and continued innovation has fueled the belief that our profession is a major contributor to unsustainable health care costs.¹¹ We now face multiple legislative regulations related to physician reimbursement, ownership, self-referral, medical liability, and mandates of the Affordable Care Act.⁹ As a result, there has been a decreasing role for orthopedic surgeons as independent practitioners, with more orthopedists forgoing physician-owned practices for large hospital corporations. We are also in increasing competition for limited resources.¹⁰ This is compounded by the fact that those regulating health care, paying for health care, and allocating research funding fail to comprehend the high societal needs for treatment of musculoskeletal diseases and injuries,⁶ which will only increase in the coming decades.¹⁴

The aforementioned challenges make our involvement at all levels of the political process more necessary than ever before.^5,9 E. Anthony Rankin⁸ reminds us, “As physicians, we cannot in good conscience allow our patients’ access to quality orthopedic care to be determined solely by the government, the insurance companies, the trial lawyers, or others…. Either we will have a voice in defining the future of health care, or it will be defined by others for us.” Our advocacy approach, however, should be very careful. Joshua Jacobs¹¹ cautions that “we will be most effective if our advocacy message is presented as a potential solution to the current health care crisis, not just as a demand for fair reimbursement.” Instead, we can achieve this goal with what Richard Gelberman² summarized as “doing what we do best: accumulating knowledge, positioning ourselves as the authorities that we are, and using what we learn to advocate for better patient care and research.”

Value Medicine

Orthopedic surgeons are now expected to provide not just high-quality care but low-cost care. In line with the emerging emphasis on value, sharp focus has been placed on the assessment of physician performance and treatment outcomes as quality-of-care measures.⁶ But how have we measured the quality of the care we provide? We have not, or, at least, we have not had valid or reliable means of doing so.⁶ Gone are the days of telling the world of the excellence of our profession in the treatment of musculoskeletal disease. We now must prove to our patients, the government, and payers that what we do works.^12,13 If we fail to communicate the cost effectiveness of our interventions, our new knowledge and technologies will not be accepted or funded.¹⁰ We should, however, not be discouraged by the new “value equation,” but use it as an incentive to provide evidence-based care and to improve the efficiency of resource utilization.¹⁴ Today, we are urged to be leaders in quality improvement, both in our individual orthopedic practices and as a profession.^10,12,13

Conclusion

Meeting increasingly higher demands for musculoskeletal care in an evolving medical landscape will bring a new set of challenges that will be more frequent and more intense than those in the past.¹⁴ Today, we are tasked with providing fiscally efficient, culturally competent, high-quality, evidence-based, and compassionate care. We are also tasked with reclaiming our ability to shape the future of our profession at the policymaking level. In doing so, the need for unity, advocacy, commitment to education and research, women and minority representation, and open communication with the public has never been more relevant. As we continue to advance as a profession, we must resist the temptation to look back in defiance of change but move forward, confident in our ability to evolve. ◾

Spondylolysis is a bone defect of the pars interarticularis. It is usually seen in adolescents who participate in sporting activities that involve repetitive axial loads to a hyperextended lower back, such as football offensive lineman, throwing athletes, and gymnasts. It occurs frequently in the L5 pars and can be unilateral or bilateral. The majority of reported multiple-level spondylolysis is at consecutive lumbar segments.^1-6 Rarely, it affects noncontiguous levels. Most patients respond well to conservative treatment in the form of activity modification and orthosis.⁷ Surgical intervention is considered if 6 months of conservative management fails, spondylolisthesis develops, or intractable neurologic symptoms arise.

This case report presents an 18-year-old man with noncontiguous spondylolysis at L2 and L5 who was successfully treated with a 1-level pars repair at L2 after failed conservative management. This unique case highlights the importance of using single-photon emission computed tomography (SPECT) scan and diagnostic pars block when planning for surgical treatment in the rare cases of noncontiguous spondylolysis. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old man presented to the clinic with worsening lower back pain for the previous 4 weeks. He was playing high school baseball and stated the pain was worse when he swung his bat. He had no history of trauma or back pain. Rest was the only alleviating factor, and he was beginning to experience pain when he stood after sitting. He denied any radicular pain. On examination, he had midline tenderness along the upper lumbar spine and pain with lumbar spine extension. His neurologic examination showed normal sensation with 5/5 strength in all key muscle groups. Plain radiograph of the lumbar spine showed an L5 pars defect (Figures 1A, 1B). A SPECT scan showed increased uptake at L2 pars bilaterally; the L5 pars did not show increased uptake (Figures 2A, 2B). A computed tomography (CT) scan confirmed bilateral L2 pars fractures and a left L5 pars fracture (Figures 3A, 3B). Bony changes in the form of marginal sclerosis at the L5, but not the L2, pars suggested that the L2 fracture was acute while the L5 fracture was chronic (Figures 4A, 4B).

The patient had conservative management for 6 months in the form of lumbosacral orthosis (LSO), cessation of sports activities, and physical therapy. The patient was initially treated with an LSO brace for 3 months, after which he had physical therapy. At 6 month follow-up, he reported continuing, significant back pain. A repeat CT scan of the lumbar spine showed no interval healing of the bilateral L2 or the unilateral L5 pars fractures. As a result of the patient’s noncontiguous pars fractures, a diagnostic CT-guided block of L2 pars was performed to identify which level was his main pain generator (Figure 5). He reported a brief period of complete pain relief after the L2 pars block. With failure of 6 months’ conservative management and positive SPECT scan and diagnostic block, surgical treatment was recommended. Prior to surgical intervention, magnetic resonance imaging was obtained to rule out pathology (eg, disc degeneration, infection, or tumor) other than the pars defect that could require fusion instead of pars repair (Figures 6A, 6B). Because of the patient’s young age, bilateral L2 pars repair rather than fusion was indicated. After 8 months of persistent back pain, he underwent bilateral L2 pars repair with iliac crest autograft, pedicle screws, and sublaminar hook fixation (Figures 7A, 7B). The patient had an uneventful immediate postoperative course. A 6-month postoperative CT scan showed bridging callus at the L2 pars; however, the left L5 pars fracture was still visible (Figures 8A-8C). Over a 6-month postoperative period, the patient had continued improvement in his back pain, advanced his activity as tolerated without problem, and was allowed to resume his sports activities. At 2-year follow-up, he was playing baseball and basketball, and denied any back pain. 

Discussion

Lumbar spondylolysis is commonly seen at the fourth and fifth lumbar vertebrae, and accounts for more than 95% of spondylolysis cases.⁸ Multiple-level spondylolysis is a relatively rare finding with an incidence varying between 1.2% and 5.6%. The majority of the reported multiple-level cases are adjacent.^1-3,6 Adolescents often present with a history of insidious-onset low back pain without radicular symptoms that is exacerbated by activity. Occasionally, an acute injury may elicit the onset of pain. A thorough history with emphasis on pain in relation to activity and sports involvement is beneficial. The patient in the current study was a throwing athlete and presented with 4 weeks of back pain that worsened with activity; he had no history of trauma.

Radiographic assessment using standing anteroposterior, lateral, and oblique radiographs of the thoracolumbar spine is useful in the initial assessment. A SPECT scan of the lumbosacral spine is highly sensitive for identifying spondylolytic defects when plain radiographs are within normal limits, yet a high index of suspicion remains given the patient’s history and physical examination findings.^9,10 Increased radionuclide uptake within the pars indicates a stress reaction and, possibly, a more acute pathology. The plain radiographs of the patient showed only L5 spondylolysis. However, a SPECT scan showed only increased uptake in L2 pars on both sides. These findings suggested chronic L5 and acute L2 pars defects. A thin-cut CT scan gives the best visualization of pars defect and can help in differentiating chronic defect with sclerotic margins versus acute defect with hazy irregular margins. In the current case, the CT scan showed changes consistent with unilateral chronic L5 and bilateral acute L2 pars defects.

The origin of the pain in spondylolysis is from the tissues rich in nociceptive nerve endings in the loose posterior arch. A CT-guided pars block is a very useful diagnostic preoperative tool that confirms the symptomatic level in cases of multilevel pars defect, especially if they are noncontiguous. In this case, the diagnostic preoperative bilateral L2 pars block confirmed that the pain generator was the acute L2 rather than the chronic L5 pars defect. This step assured that surgical treatment involving only the L2 level would be beneficial in alleviating the patient’s back pain after the failure of 6 months of conservative treatment.

Most patients with single-level spondylolysis respond to conservative treatment, especially after early diagnosis and treatment. The traditional nonoperative treatment of children and adolescents with a symptomatic spondylolytic lesion was a period of rest and progressive increased activity with physical therapy. Immobilization with an LSO was reserved for individuals who did not respond to rest and physical therapy.¹¹ However, multiple studies revealed early immobilization achieved results superior to activity restriction alone, and individuals who underwent a period of activity restriction prior to bracing were more likely to experience persistent symptoms.^12-14 Our patient underwent conservative treatment for 6 months, in the form of LSO, cessation of sport activities, and physical therapy, which failed to give him relief of his back pain.

Surgical intervention is warranted for adolescents with persistent, debilitating pain intractable to at least a 6-month period of nonoperative management. Additional indications for surgical management are those individuals who present with neurologic deficits and isthmic spondylolisthesis. Surgical treatment involves direct pars repair with iliac crest bone graft and use of a sublaminar hook/pedicle screw construct, cerclage wire, or pars screw.^15-18 

In contrast to single-level pars defects that respond well to conservative treatment, there are conflicting reports regarding the management of multiple-level pars fractures; a few reports suggest good outcome with conservative management, but the majority state that surgery is often required and conservative measures are rarely useful.^1-4,6 Nayeemuddin and colleagues¹⁹ reported a case of a 16-year-old football player who presented with a 4-month history of constant low back pain related to bilateral L3 and L5 pars defects that responded to 1 year of conservative management, when the more acute fractures at L3 showed complete bony union and the patient had symptomatic pain relief and was able to return to full sporting activity.

 Chang and colleagues² reported 10 patients with adjacent 2-level bilateral spondylolysis treated successfully using a pedicle screw–hook construct with autogenous bone grafting. Ogawa and colleagues⁵ reported adjacent 2-level spondylolysis in 5 patients and 3-level spondylolysis in 2 patients, who were treated successfully by segmental wire fixation and bone grafting. Ivanic and colleagues¹⁵ retrospectively reviewed 113 patients with spondylolysis who were treated with direct repair using a hook-screw construct and showed a pseudoarthrosis rate of 13.3%. Superior fusion rates were observed in patients 14 years and younger compared with older patients, particularly those 20 years and older.¹⁵ Roca and colleagues¹⁶ prospectively analyzed 19 consecutive cases of spondylolysis that were repaired using a hook-screw construct. Twelve of 13 patients (92%) who were 20 years or younger at the time of the study (average age, 17.2 years) had fusion, whereas, in 6 patients 21 years and older (average age, 27.5 years), no cases of fusion were observed. The patients 20 years or younger had significantly better clinical results than those obtained in the patients 21 years and older. The authors concluded that pedicle screw–hook fixation is a useful alternative in the treatment of spondylolysis in adolescents, but did not recommend this procedure in patients older than 20 years.¹⁶

Conclusion

The current case demonstrates a unique example of rare noncontiguous pars defects successfully treated with primary repair of 1 level when conservative management failed and the symptomatic defect was isolated. It also highlights the importance of investigating the entirety of the lumbar spine when diagnosis of L5 spondylolysis rules out noncontiguous pars defects. The treatment of noncontiguous pars defects is not well defined; this case showed the importance of using a SPECT scan and a diagnostic pars block to help isolate the symptomatic level when surgical management is considered after a failure of conservative treatment. This case shows 2 possible results: the chronic unilateral L5 defect responded to nonsurgical treatment with asymptomatic fibrous nonunion, while the more acute bilateral L2 defect responded to pars repair with pedicle screw–hook fixation and iliac crest bone graft. 

Spondylolysis is a bone defect of the pars interarticularis. It is usually seen in adolescents who participate in sporting activities that involve repetitive axial loads to a hyperextended lower back, such as football offensive lineman, throwing athletes, and gymnasts. It occurs frequently in the L5 pars and can be unilateral or bilateral. The majority of reported multiple-level spondylolysis is at consecutive lumbar segments.^1-6 Rarely, it affects noncontiguous levels. Most patients respond well to conservative treatment in the form of activity modification and orthosis.⁷ Surgical intervention is considered if 6 months of conservative management fails, spondylolisthesis develops, or intractable neurologic symptoms arise.

This case report presents an 18-year-old man with noncontiguous spondylolysis at L2 and L5 who was successfully treated with a 1-level pars repair at L2 after failed conservative management. This unique case highlights the importance of using single-photon emission computed tomography (SPECT) scan and diagnostic pars block when planning for surgical treatment in the rare cases of noncontiguous spondylolysis. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old man presented to the clinic with worsening lower back pain for the previous 4 weeks. He was playing high school baseball and stated the pain was worse when he swung his bat. He had no history of trauma or back pain. Rest was the only alleviating factor, and he was beginning to experience pain when he stood after sitting. He denied any radicular pain. On examination, he had midline tenderness along the upper lumbar spine and pain with lumbar spine extension. His neurologic examination showed normal sensation with 5/5 strength in all key muscle groups. Plain radiograph of the lumbar spine showed an L5 pars defect (Figures 1A, 1B). A SPECT scan showed increased uptake at L2 pars bilaterally; the L5 pars did not show increased uptake (Figures 2A, 2B). A computed tomography (CT) scan confirmed bilateral L2 pars fractures and a left L5 pars fracture (Figures 3A, 3B). Bony changes in the form of marginal sclerosis at the L5, but not the L2, pars suggested that the L2 fracture was acute while the L5 fracture was chronic (Figures 4A, 4B).

The patient had conservative management for 6 months in the form of lumbosacral orthosis (LSO), cessation of sports activities, and physical therapy. The patient was initially treated with an LSO brace for 3 months, after which he had physical therapy. At 6 month follow-up, he reported continuing, significant back pain. A repeat CT scan of the lumbar spine showed no interval healing of the bilateral L2 or the unilateral L5 pars fractures. As a result of the patient’s noncontiguous pars fractures, a diagnostic CT-guided block of L2 pars was performed to identify which level was his main pain generator (Figure 5). He reported a brief period of complete pain relief after the L2 pars block. With failure of 6 months’ conservative management and positive SPECT scan and diagnostic block, surgical treatment was recommended. Prior to surgical intervention, magnetic resonance imaging was obtained to rule out pathology (eg, disc degeneration, infection, or tumor) other than the pars defect that could require fusion instead of pars repair (Figures 6A, 6B). Because of the patient’s young age, bilateral L2 pars repair rather than fusion was indicated. After 8 months of persistent back pain, he underwent bilateral L2 pars repair with iliac crest autograft, pedicle screws, and sublaminar hook fixation (Figures 7A, 7B). The patient had an uneventful immediate postoperative course. A 6-month postoperative CT scan showed bridging callus at the L2 pars; however, the left L5 pars fracture was still visible (Figures 8A-8C). Over a 6-month postoperative period, the patient had continued improvement in his back pain, advanced his activity as tolerated without problem, and was allowed to resume his sports activities. At 2-year follow-up, he was playing baseball and basketball, and denied any back pain. 

Discussion

Lumbar spondylolysis is commonly seen at the fourth and fifth lumbar vertebrae, and accounts for more than 95% of spondylolysis cases.⁸ Multiple-level spondylolysis is a relatively rare finding with an incidence varying between 1.2% and 5.6%. The majority of the reported multiple-level cases are adjacent.^1-3,6 Adolescents often present with a history of insidious-onset low back pain without radicular symptoms that is exacerbated by activity. Occasionally, an acute injury may elicit the onset of pain. A thorough history with emphasis on pain in relation to activity and sports involvement is beneficial. The patient in the current study was a throwing athlete and presented with 4 weeks of back pain that worsened with activity; he had no history of trauma.

Radiographic assessment using standing anteroposterior, lateral, and oblique radiographs of the thoracolumbar spine is useful in the initial assessment. A SPECT scan of the lumbosacral spine is highly sensitive for identifying spondylolytic defects when plain radiographs are within normal limits, yet a high index of suspicion remains given the patient’s history and physical examination findings.^9,10 Increased radionuclide uptake within the pars indicates a stress reaction and, possibly, a more acute pathology. The plain radiographs of the patient showed only L5 spondylolysis. However, a SPECT scan showed only increased uptake in L2 pars on both sides. These findings suggested chronic L5 and acute L2 pars defects. A thin-cut CT scan gives the best visualization of pars defect and can help in differentiating chronic defect with sclerotic margins versus acute defect with hazy irregular margins. In the current case, the CT scan showed changes consistent with unilateral chronic L5 and bilateral acute L2 pars defects.

The origin of the pain in spondylolysis is from the tissues rich in nociceptive nerve endings in the loose posterior arch. A CT-guided pars block is a very useful diagnostic preoperative tool that confirms the symptomatic level in cases of multilevel pars defect, especially if they are noncontiguous. In this case, the diagnostic preoperative bilateral L2 pars block confirmed that the pain generator was the acute L2 rather than the chronic L5 pars defect. This step assured that surgical treatment involving only the L2 level would be beneficial in alleviating the patient’s back pain after the failure of 6 months of conservative treatment.

Most patients with single-level spondylolysis respond to conservative treatment, especially after early diagnosis and treatment. The traditional nonoperative treatment of children and adolescents with a symptomatic spondylolytic lesion was a period of rest and progressive increased activity with physical therapy. Immobilization with an LSO was reserved for individuals who did not respond to rest and physical therapy.¹¹ However, multiple studies revealed early immobilization achieved results superior to activity restriction alone, and individuals who underwent a period of activity restriction prior to bracing were more likely to experience persistent symptoms.^12-14 Our patient underwent conservative treatment for 6 months, in the form of LSO, cessation of sport activities, and physical therapy, which failed to give him relief of his back pain.

Surgical intervention is warranted for adolescents with persistent, debilitating pain intractable to at least a 6-month period of nonoperative management. Additional indications for surgical management are those individuals who present with neurologic deficits and isthmic spondylolisthesis. Surgical treatment involves direct pars repair with iliac crest bone graft and use of a sublaminar hook/pedicle screw construct, cerclage wire, or pars screw.^15-18 

In contrast to single-level pars defects that respond well to conservative treatment, there are conflicting reports regarding the management of multiple-level pars fractures; a few reports suggest good outcome with conservative management, but the majority state that surgery is often required and conservative measures are rarely useful.^1-4,6 Nayeemuddin and colleagues¹⁹ reported a case of a 16-year-old football player who presented with a 4-month history of constant low back pain related to bilateral L3 and L5 pars defects that responded to 1 year of conservative management, when the more acute fractures at L3 showed complete bony union and the patient had symptomatic pain relief and was able to return to full sporting activity.

 Chang and colleagues² reported 10 patients with adjacent 2-level bilateral spondylolysis treated successfully using a pedicle screw–hook construct with autogenous bone grafting. Ogawa and colleagues⁵ reported adjacent 2-level spondylolysis in 5 patients and 3-level spondylolysis in 2 patients, who were treated successfully by segmental wire fixation and bone grafting. Ivanic and colleagues¹⁵ retrospectively reviewed 113 patients with spondylolysis who were treated with direct repair using a hook-screw construct and showed a pseudoarthrosis rate of 13.3%. Superior fusion rates were observed in patients 14 years and younger compared with older patients, particularly those 20 years and older.¹⁵ Roca and colleagues¹⁶ prospectively analyzed 19 consecutive cases of spondylolysis that were repaired using a hook-screw construct. Twelve of 13 patients (92%) who were 20 years or younger at the time of the study (average age, 17.2 years) had fusion, whereas, in 6 patients 21 years and older (average age, 27.5 years), no cases of fusion were observed. The patients 20 years or younger had significantly better clinical results than those obtained in the patients 21 years and older. The authors concluded that pedicle screw–hook fixation is a useful alternative in the treatment of spondylolysis in adolescents, but did not recommend this procedure in patients older than 20 years.¹⁶

Conclusion

The current case demonstrates a unique example of rare noncontiguous pars defects successfully treated with primary repair of 1 level when conservative management failed and the symptomatic defect was isolated. It also highlights the importance of investigating the entirety of the lumbar spine when diagnosis of L5 spondylolysis rules out noncontiguous pars defects. The treatment of noncontiguous pars defects is not well defined; this case showed the importance of using a SPECT scan and a diagnostic pars block to help isolate the symptomatic level when surgical management is considered after a failure of conservative treatment. This case shows 2 possible results: the chronic unilateral L5 defect responded to nonsurgical treatment with asymptomatic fibrous nonunion, while the more acute bilateral L2 defect responded to pars repair with pedicle screw–hook fixation and iliac crest bone graft. 

Spondylolysis is a bone defect of the pars interarticularis. It is usually seen in adolescents who participate in sporting activities that involve repetitive axial loads to a hyperextended lower back, such as football offensive lineman, throwing athletes, and gymnasts. It occurs frequently in the L5 pars and can be unilateral or bilateral. The majority of reported multiple-level spondylolysis is at consecutive lumbar segments.^1-6 Rarely, it affects noncontiguous levels. Most patients respond well to conservative treatment in the form of activity modification and orthosis.⁷ Surgical intervention is considered if 6 months of conservative management fails, spondylolisthesis develops, or intractable neurologic symptoms arise.

This case report presents an 18-year-old man with noncontiguous spondylolysis at L2 and L5 who was successfully treated with a 1-level pars repair at L2 after failed conservative management. This unique case highlights the importance of using single-photon emission computed tomography (SPECT) scan and diagnostic pars block when planning for surgical treatment in the rare cases of noncontiguous spondylolysis. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old man presented to the clinic with worsening lower back pain for the previous 4 weeks. He was playing high school baseball and stated the pain was worse when he swung his bat. He had no history of trauma or back pain. Rest was the only alleviating factor, and he was beginning to experience pain when he stood after sitting. He denied any radicular pain. On examination, he had midline tenderness along the upper lumbar spine and pain with lumbar spine extension. His neurologic examination showed normal sensation with 5/5 strength in all key muscle groups. Plain radiograph of the lumbar spine showed an L5 pars defect (Figures 1A, 1B). A SPECT scan showed increased uptake at L2 pars bilaterally; the L5 pars did not show increased uptake (Figures 2A, 2B). A computed tomography (CT) scan confirmed bilateral L2 pars fractures and a left L5 pars fracture (Figures 3A, 3B). Bony changes in the form of marginal sclerosis at the L5, but not the L2, pars suggested that the L2 fracture was acute while the L5 fracture was chronic (Figures 4A, 4B).

The patient had conservative management for 6 months in the form of lumbosacral orthosis (LSO), cessation of sports activities, and physical therapy. The patient was initially treated with an LSO brace for 3 months, after which he had physical therapy. At 6 month follow-up, he reported continuing, significant back pain. A repeat CT scan of the lumbar spine showed no interval healing of the bilateral L2 or the unilateral L5 pars fractures. As a result of the patient’s noncontiguous pars fractures, a diagnostic CT-guided block of L2 pars was performed to identify which level was his main pain generator (Figure 5). He reported a brief period of complete pain relief after the L2 pars block. With failure of 6 months’ conservative management and positive SPECT scan and diagnostic block, surgical treatment was recommended. Prior to surgical intervention, magnetic resonance imaging was obtained to rule out pathology (eg, disc degeneration, infection, or tumor) other than the pars defect that could require fusion instead of pars repair (Figures 6A, 6B). Because of the patient’s young age, bilateral L2 pars repair rather than fusion was indicated. After 8 months of persistent back pain, he underwent bilateral L2 pars repair with iliac crest autograft, pedicle screws, and sublaminar hook fixation (Figures 7A, 7B). The patient had an uneventful immediate postoperative course. A 6-month postoperative CT scan showed bridging callus at the L2 pars; however, the left L5 pars fracture was still visible (Figures 8A-8C). Over a 6-month postoperative period, the patient had continued improvement in his back pain, advanced his activity as tolerated without problem, and was allowed to resume his sports activities. At 2-year follow-up, he was playing baseball and basketball, and denied any back pain. 

Discussion

Lumbar spondylolysis is commonly seen at the fourth and fifth lumbar vertebrae, and accounts for more than 95% of spondylolysis cases.⁸ Multiple-level spondylolysis is a relatively rare finding with an incidence varying between 1.2% and 5.6%. The majority of the reported multiple-level cases are adjacent.^1-3,6 Adolescents often present with a history of insidious-onset low back pain without radicular symptoms that is exacerbated by activity. Occasionally, an acute injury may elicit the onset of pain. A thorough history with emphasis on pain in relation to activity and sports involvement is beneficial. The patient in the current study was a throwing athlete and presented with 4 weeks of back pain that worsened with activity; he had no history of trauma.

Radiographic assessment using standing anteroposterior, lateral, and oblique radiographs of the thoracolumbar spine is useful in the initial assessment. A SPECT scan of the lumbosacral spine is highly sensitive for identifying spondylolytic defects when plain radiographs are within normal limits, yet a high index of suspicion remains given the patient’s history and physical examination findings.^9,10 Increased radionuclide uptake within the pars indicates a stress reaction and, possibly, a more acute pathology. The plain radiographs of the patient showed only L5 spondylolysis. However, a SPECT scan showed only increased uptake in L2 pars on both sides. These findings suggested chronic L5 and acute L2 pars defects. A thin-cut CT scan gives the best visualization of pars defect and can help in differentiating chronic defect with sclerotic margins versus acute defect with hazy irregular margins. In the current case, the CT scan showed changes consistent with unilateral chronic L5 and bilateral acute L2 pars defects.

The origin of the pain in spondylolysis is from the tissues rich in nociceptive nerve endings in the loose posterior arch. A CT-guided pars block is a very useful diagnostic preoperative tool that confirms the symptomatic level in cases of multilevel pars defect, especially if they are noncontiguous. In this case, the diagnostic preoperative bilateral L2 pars block confirmed that the pain generator was the acute L2 rather than the chronic L5 pars defect. This step assured that surgical treatment involving only the L2 level would be beneficial in alleviating the patient’s back pain after the failure of 6 months of conservative treatment.

Most patients with single-level spondylolysis respond to conservative treatment, especially after early diagnosis and treatment. The traditional nonoperative treatment of children and adolescents with a symptomatic spondylolytic lesion was a period of rest and progressive increased activity with physical therapy. Immobilization with an LSO was reserved for individuals who did not respond to rest and physical therapy.¹¹ However, multiple studies revealed early immobilization achieved results superior to activity restriction alone, and individuals who underwent a period of activity restriction prior to bracing were more likely to experience persistent symptoms.^12-14 Our patient underwent conservative treatment for 6 months, in the form of LSO, cessation of sport activities, and physical therapy, which failed to give him relief of his back pain.

Surgical intervention is warranted for adolescents with persistent, debilitating pain intractable to at least a 6-month period of nonoperative management. Additional indications for surgical management are those individuals who present with neurologic deficits and isthmic spondylolisthesis. Surgical treatment involves direct pars repair with iliac crest bone graft and use of a sublaminar hook/pedicle screw construct, cerclage wire, or pars screw.^15-18 

In contrast to single-level pars defects that respond well to conservative treatment, there are conflicting reports regarding the management of multiple-level pars fractures; a few reports suggest good outcome with conservative management, but the majority state that surgery is often required and conservative measures are rarely useful.^1-4,6 Nayeemuddin and colleagues¹⁹ reported a case of a 16-year-old football player who presented with a 4-month history of constant low back pain related to bilateral L3 and L5 pars defects that responded to 1 year of conservative management, when the more acute fractures at L3 showed complete bony union and the patient had symptomatic pain relief and was able to return to full sporting activity.

 Chang and colleagues² reported 10 patients with adjacent 2-level bilateral spondylolysis treated successfully using a pedicle screw–hook construct with autogenous bone grafting. Ogawa and colleagues⁵ reported adjacent 2-level spondylolysis in 5 patients and 3-level spondylolysis in 2 patients, who were treated successfully by segmental wire fixation and bone grafting. Ivanic and colleagues¹⁵ retrospectively reviewed 113 patients with spondylolysis who were treated with direct repair using a hook-screw construct and showed a pseudoarthrosis rate of 13.3%. Superior fusion rates were observed in patients 14 years and younger compared with older patients, particularly those 20 years and older.¹⁵ Roca and colleagues¹⁶ prospectively analyzed 19 consecutive cases of spondylolysis that were repaired using a hook-screw construct. Twelve of 13 patients (92%) who were 20 years or younger at the time of the study (average age, 17.2 years) had fusion, whereas, in 6 patients 21 years and older (average age, 27.5 years), no cases of fusion were observed. The patients 20 years or younger had significantly better clinical results than those obtained in the patients 21 years and older. The authors concluded that pedicle screw–hook fixation is a useful alternative in the treatment of spondylolysis in adolescents, but did not recommend this procedure in patients older than 20 years.¹⁶

Conclusion

The current case demonstrates a unique example of rare noncontiguous pars defects successfully treated with primary repair of 1 level when conservative management failed and the symptomatic defect was isolated. It also highlights the importance of investigating the entirety of the lumbar spine when diagnosis of L5 spondylolysis rules out noncontiguous pars defects. The treatment of noncontiguous pars defects is not well defined; this case showed the importance of using a SPECT scan and a diagnostic pars block to help isolate the symptomatic level when surgical management is considered after a failure of conservative treatment. This case shows 2 possible results: the chronic unilateral L5 defect responded to nonsurgical treatment with asymptomatic fibrous nonunion, while the more acute bilateral L2 defect responded to pars repair with pedicle screw–hook fixation and iliac crest bone graft. 

Vancomycin is a glycopeptide antibiotic that exhibits bactericidal activity against gram-positive cocci. It is commonly recommended for surgical prophylaxis in cases of suspected bacterial resistance or penicillin allergy.¹ Two main types of hypersensitivity reactions associated with vancomycin can have similar presentations. Red man syndrome is an anaphylactoid reaction caused by direct release of histamine from mast cells via a nonimmunologic mechanism, and is the more common of the 2 reactions. The second type is an anaphylactic reaction, which is an immunoglobulin E (IgE)–mediated systemic event and requires exposure to become sensitized.^2,3

We present a patient who had received vancomycin on at least 12 occasions without incident. On this occasion, however, she developed a true anaphylactic reaction causing acute hemodynamic collapse that she survived after extensive resuscitation. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 55-year-old woman had a history of metastatic giant cell tumor of the right proximal tibia. She was originally treated 27 years ago for proximal tibial resection and reconstruction with a custom proximal tibial prosthesis. Four months later, she underwent resection of multiple pulmonary metastases via bilateral thoracotomies in a single surgical setting. After this, the patient had no evidence of recurrent metastatic disease. In subsequent years, the patient underwent multiple revision surgeries for problems such as hardware failure, patellar maltracking, and infection. The patient underwent 19 operations, including several nonorthopedic procedures. Because the patient had a rash after receiving penicillin as a child, she was thought to be allergic to penicillin. Consequently, she received vancomycin as antibiotic prophylaxis for the majority of these procedures. She also received extended courses of vancomycin of at least 6 weeks on 2 separate occasions. During her most recent revision procedure, 6 weeks prior to the procedure under discussion, the patient took vancomycin without incident. She was then found to have a prosthetic infection with Staphylococcus epidermidis, the same organism isolated in her previous infections, and she was advised to undergo a staged revision.

After a preoperative medical evaluation by her primary care physician, the patient was taken to the operating room for prosthesis removal and antibiotic spacer placement. She was anemic with a hemoglobin level of 8.8 g/dL; her erythrocyte sedimentation rate (ESR) was 102 mm/h (normal, <22 mm/h) and her C-reactive protein (CRP) was 38 mg/L (normal, <3 mg/L), but, otherwise, her laboratory values were normal, including a white blood cell count (WBC) of 8100/µL. Her electrocardiogram showed a normal sinus rhythm with nonspecific ST- and T-wave changes. Antibiotics were held until after cultures were taken. General endotracheal tube anesthesia was induced with 2 mg midazolam, 100 µg fentanyl, 180 mg propofol, and 140 mg succinylcholine, followed by 10 mg vecuronium, and maintained with desflurane. A tourniquet was not used per the surgeon’s routine. Dissection was carried down to the prosthesis and showed a small amount of purulent fluid. Transfusion of 1 unit of packed red blood cells (pRBC) was started during the approach owing to relatively low preoperative hemoglobin and significant blood loss. Approximately 500 mL of blood was lost during the approach secondary to the extensive dissection and the local inflammatory response from infection and recent surgery. After cultures were taken, and approximately 10 minutes after blood transfusion began, infusion of 1 g vancomycin in 250 mL normal saline was started via an infusion pump to run over 1 hour.

After infusion of 5 mL vancomycin, the patient’s blood pressure dropped from 117/63 mm Hg to 63/30 mm Hg; her pulse concurrently dropped from 90 to 50 beats/min. Vancomycin infusion was immediately stopped, anesthesia gasses were turned off, and patient received a bolus of normal saline with a second unit of pRBC. Patient received boluses of 0.5 mg to 1.0 mg epinephrine and 100 µg phenylephrine without sustained increase in blood pressure, which had dropped to 54/24 mm Hg, although the patient became tachycardic to ~120 beats/min after epinephrine. A sudden drop in end-tidal CO₂ from 40s mm Hg to 20s mm Hg was also noted, indicating continuous but significantly decreased perfusion of the lungs.

We elected to abort the procedure, and a vacuum-assisted closure (VAC) dressing was applied to the open wound. After 15 minutes, the patient’s pulses, which had been faint, became impalpable, and cardiopulmonary resuscitation was initiated for about 7 minutes. The patient received 40 units vasopressin with repeated boluses of 0.5 mg epinephrine; a norepinephrine continuous infusion was started with the return of pulses. The patient also received 50 mg diphenhydramine, 125 mg methylprednisolone, and 20 mg famotidine for suspected anaphylaxis. A central venous line and arterial line were placed, and blood was drawn for laboratory analysis. The patient was noted to have clear breath sounds with no obvious rash, and her urine remained clear. Blood gas showed a profound metabolic acidosis, with pH of 7.09, base deficit of 5.9, and lactate of 8.9. The patient was treated with bicarbonate infusion. The patient was noted to ooze significantly during central venous line and arterial line placement, despite apparently normal coagulation during the surgical approach. Coagulation values were consistent with disseminated intravascular coagulation (DIC): prothrombin time, 57 s (international normalized ratio, 6.7); partial thromboplastin time, >200 s; thrombin time, 110 s; D-dimer, >10,000 ng/mL (normal, 0-200 ng/mL); and fibrinogen, <60 mg/dL (normal, 222-475 mg/dL). The patient’s thromboelastogram showed a flat line indicating an absence of clotting. Interestingly, the platelet count remained near the preoperative level at 338×10³/µL. The patient’s blood pressure remained labile and was responsive primarily to epinephrine boluses, of which she received a total of 5 mg. After 1 hour of resuscitation, during which time the patient received a total of 5 L crystalloid and 3 units pRBC, the patient was transferred to the intensive care unit (ICU), intubated, and started on a titrated epinephrine infusion.

Upon arrival in the ICU, the patient quickly stabilized hemodynamically. She was weaned from all inotropic support within 2 hours of arrival. The patient lost 800 mL of blood through wound VAC over the first 12 hours postoperatively and required a total of 11 units of pRBC, 6 units fresh frozen plasma, and 3 units of pooled cryoprecipitate, all of which were compatible. Laboratory values, including arterial pH, lactic acid, and coagulation studies, normalized on the evening of surgery, and, by the next morning, the patient was alert and was extubated without difficulty. Steroids were tapered without hemodynamic compromise while the patient was in the ICU. Cardiology examination revealed no abnormalities. Because of the temporal association of blood transfusion with cardiovascular collapse, pRBC units were retested for antibodies and cultured. Both of these investigations were negative. Wound cultures again were positive for Staphylococcus epidermidis, and blood cultures were negative. The patient was started on daptomycin based on susceptibility profiles. Serum histamine levels taken during initial resuscitation in the operating room were normal. The serum tryptase level obtained at the same time was markedly elevated at >700 ng/mL (normal, <11.5 ng/mL), although this information was not available until several days later.

The patient underwent 2 additional surgeries during the same admission, including the prosthesis removal and tobramycin cement spacer placement, without incident. She was discharged home, again without incident. The patient was later evaluated by an outside allergist and underwent skin puncture and intradermal allergy testing. The results were consistent with a strong IgE-mediated hypersensitivity. Interestingly, she was found not to have a penicillin allergy.

Discussion

Vancomycin hypersensitivity reactions include the anaphylactoid reaction red man syndrome and a true IgE-mediated anaphylactic reaction. Red man syndrome is much more common, with reported rates in infected patients from 3.7% to 47%,^4,5 when vancomycin is given at the suggested  rate of 1 g over 1 hour. The reaction occurs because of histamine release from mast cells and basophils, and does not require previous sensitization.³ The rate of infusion is directly related to the development of symptoms, with 100% of patients developing symptoms in 1 study with rapid infusion (1 g over 10 min).⁶ Red man syndrome can typically be prevented by slowing the rate of infusion or by giving an H₁ blocker.³ Anaphylaxis is more rare but can occur.⁷ Anaphylaxis is mediated by vancomycin-specific IgE, which requires previous exposure, as was the case with our patient. Interestingly, the patient had received vancomycin many times without any signs of a hypersensitivity reaction. Antihistamines are not effective in treating anaphylaxis, and epinephrine is the first-line agent.³ This was clearly demonstrated in this case, as there was a significant hemodynamic response to epinephrine and a negligible response to other vasopressors, specifically norepinephrine and vasopressin.

Most hypersensitivity reactions during the course of a surgical procedure occur with induction of anesthesia, with neuromuscular blocking agents and antibiotics being the most common causes.⁸ In our case, antibiotics were held until after deep cultures were taken. Given the time from induction to the anaphylactic reaction, it is unlikely the reaction resulted from the induction agents or the neuromuscular blocking agent. The possibility of a transfusion reaction was also investigated, since a unit of pRBC was still being transfused when symptoms began. An acute hemolytic transfusion reaction has the classic triad of fever, flank pain, and hemoglobinuria, and can also present as DIC.⁹ Under anesthesia, DIC can often be the presenting sign. In this case, a hemolytic transfusion reaction appeared very unlikely. All of the blood components the patient received were rechecked and found to be compatible, posttransfusion analysis showed no evidence of hemolysis in any sample, and the direct antiglobulin test was negative in all components.

To our knowledge, there are no reported cases of vancomycin-induced anaphylaxis with concomitant DIC. Symptoms of anaphylaxis after exposure to a possible antigen include rapid onset of hypotension or rapid onset of signs in at least 2 organ systems, including cutaneous, gastrointestinal, respiratory, and cardiovascular.¹⁰ Anaphylaxis with DIC is rare after exposure to any substance but has been reported.¹¹ In fact, induction of systemic anaphylaxis in mice is known to cause DIC, with platelet-activating factor suggested as an important common mediator. A similar mechanism is suspected in humans.¹²

Confirmation of, and, certainly, prediction of, a vancomycin hypersensitivity reaction is difficult. Histamine levels can be used as a measure of mast-cell degranulation, but serum levels peak within 5 minutes and quickly return to baseline, limiting its diagnostic usefulness.³ Tryptase is an enzyme found in the secretory granules of mast cells. It has become an accepted marker of acute anaphylaxis, and, in vancomycin hypersensitivity reactions, can also distinguish between anaphylactic and anaphylactoid reactions.¹³ Tryptase levels peak 1 to 2 hours after the reaction, making this easier to measure than histamine, but results may not be available for several days, making it useful only in retrospect, as in our case. Skin testing is probably the best way to confirm a hypersensitivity reaction, although even this has been questioned with vancomycin because some find a high false-positive rate³, while others think the false-negative rate is likely too high.⁷ In this case, we were able to confirm our initial clinical suspicion with both an elevated tryptase level and a positive skin test.

Conclusion

We present a rare case of vancomycin anaphylaxis with DIC after repeated and prolonged previous exposure, which was treated acutely with hemodynamic resuscitation, replacement of blood components, steroids, and, most importantly, repeated boluses of epinephrine. Although several papers have described successful vancomycin desensitization⁷, this was fortunately not necessary in this case because the causative organism was sensitive to other acceptable antibiotics. The patient has been treated with systemic daptomycin and a tobramycin cement spacer without further incident.

Vancomycin is a glycopeptide antibiotic that exhibits bactericidal activity against gram-positive cocci. It is commonly recommended for surgical prophylaxis in cases of suspected bacterial resistance or penicillin allergy.¹ Two main types of hypersensitivity reactions associated with vancomycin can have similar presentations. Red man syndrome is an anaphylactoid reaction caused by direct release of histamine from mast cells via a nonimmunologic mechanism, and is the more common of the 2 reactions. The second type is an anaphylactic reaction, which is an immunoglobulin E (IgE)–mediated systemic event and requires exposure to become sensitized.^2,3

We present a patient who had received vancomycin on at least 12 occasions without incident. On this occasion, however, she developed a true anaphylactic reaction causing acute hemodynamic collapse that she survived after extensive resuscitation. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 55-year-old woman had a history of metastatic giant cell tumor of the right proximal tibia. She was originally treated 27 years ago for proximal tibial resection and reconstruction with a custom proximal tibial prosthesis. Four months later, she underwent resection of multiple pulmonary metastases via bilateral thoracotomies in a single surgical setting. After this, the patient had no evidence of recurrent metastatic disease. In subsequent years, the patient underwent multiple revision surgeries for problems such as hardware failure, patellar maltracking, and infection. The patient underwent 19 operations, including several nonorthopedic procedures. Because the patient had a rash after receiving penicillin as a child, she was thought to be allergic to penicillin. Consequently, she received vancomycin as antibiotic prophylaxis for the majority of these procedures. She also received extended courses of vancomycin of at least 6 weeks on 2 separate occasions. During her most recent revision procedure, 6 weeks prior to the procedure under discussion, the patient took vancomycin without incident. She was then found to have a prosthetic infection with Staphylococcus epidermidis, the same organism isolated in her previous infections, and she was advised to undergo a staged revision.

After a preoperative medical evaluation by her primary care physician, the patient was taken to the operating room for prosthesis removal and antibiotic spacer placement. She was anemic with a hemoglobin level of 8.8 g/dL; her erythrocyte sedimentation rate (ESR) was 102 mm/h (normal, <22 mm/h) and her C-reactive protein (CRP) was 38 mg/L (normal, <3 mg/L), but, otherwise, her laboratory values were normal, including a white blood cell count (WBC) of 8100/µL. Her electrocardiogram showed a normal sinus rhythm with nonspecific ST- and T-wave changes. Antibiotics were held until after cultures were taken. General endotracheal tube anesthesia was induced with 2 mg midazolam, 100 µg fentanyl, 180 mg propofol, and 140 mg succinylcholine, followed by 10 mg vecuronium, and maintained with desflurane. A tourniquet was not used per the surgeon’s routine. Dissection was carried down to the prosthesis and showed a small amount of purulent fluid. Transfusion of 1 unit of packed red blood cells (pRBC) was started during the approach owing to relatively low preoperative hemoglobin and significant blood loss. Approximately 500 mL of blood was lost during the approach secondary to the extensive dissection and the local inflammatory response from infection and recent surgery. After cultures were taken, and approximately 10 minutes after blood transfusion began, infusion of 1 g vancomycin in 250 mL normal saline was started via an infusion pump to run over 1 hour.

After infusion of 5 mL vancomycin, the patient’s blood pressure dropped from 117/63 mm Hg to 63/30 mm Hg; her pulse concurrently dropped from 90 to 50 beats/min. Vancomycin infusion was immediately stopped, anesthesia gasses were turned off, and patient received a bolus of normal saline with a second unit of pRBC. Patient received boluses of 0.5 mg to 1.0 mg epinephrine and 100 µg phenylephrine without sustained increase in blood pressure, which had dropped to 54/24 mm Hg, although the patient became tachycardic to ~120 beats/min after epinephrine. A sudden drop in end-tidal CO₂ from 40s mm Hg to 20s mm Hg was also noted, indicating continuous but significantly decreased perfusion of the lungs.

We elected to abort the procedure, and a vacuum-assisted closure (VAC) dressing was applied to the open wound. After 15 minutes, the patient’s pulses, which had been faint, became impalpable, and cardiopulmonary resuscitation was initiated for about 7 minutes. The patient received 40 units vasopressin with repeated boluses of 0.5 mg epinephrine; a norepinephrine continuous infusion was started with the return of pulses. The patient also received 50 mg diphenhydramine, 125 mg methylprednisolone, and 20 mg famotidine for suspected anaphylaxis. A central venous line and arterial line were placed, and blood was drawn for laboratory analysis. The patient was noted to have clear breath sounds with no obvious rash, and her urine remained clear. Blood gas showed a profound metabolic acidosis, with pH of 7.09, base deficit of 5.9, and lactate of 8.9. The patient was treated with bicarbonate infusion. The patient was noted to ooze significantly during central venous line and arterial line placement, despite apparently normal coagulation during the surgical approach. Coagulation values were consistent with disseminated intravascular coagulation (DIC): prothrombin time, 57 s (international normalized ratio, 6.7); partial thromboplastin time, >200 s; thrombin time, 110 s; D-dimer, >10,000 ng/mL (normal, 0-200 ng/mL); and fibrinogen, <60 mg/dL (normal, 222-475 mg/dL). The patient’s thromboelastogram showed a flat line indicating an absence of clotting. Interestingly, the platelet count remained near the preoperative level at 338×10³/µL. The patient’s blood pressure remained labile and was responsive primarily to epinephrine boluses, of which she received a total of 5 mg. After 1 hour of resuscitation, during which time the patient received a total of 5 L crystalloid and 3 units pRBC, the patient was transferred to the intensive care unit (ICU), intubated, and started on a titrated epinephrine infusion.

Upon arrival in the ICU, the patient quickly stabilized hemodynamically. She was weaned from all inotropic support within 2 hours of arrival. The patient lost 800 mL of blood through wound VAC over the first 12 hours postoperatively and required a total of 11 units of pRBC, 6 units fresh frozen plasma, and 3 units of pooled cryoprecipitate, all of which were compatible. Laboratory values, including arterial pH, lactic acid, and coagulation studies, normalized on the evening of surgery, and, by the next morning, the patient was alert and was extubated without difficulty. Steroids were tapered without hemodynamic compromise while the patient was in the ICU. Cardiology examination revealed no abnormalities. Because of the temporal association of blood transfusion with cardiovascular collapse, pRBC units were retested for antibodies and cultured. Both of these investigations were negative. Wound cultures again were positive for Staphylococcus epidermidis, and blood cultures were negative. The patient was started on daptomycin based on susceptibility profiles. Serum histamine levels taken during initial resuscitation in the operating room were normal. The serum tryptase level obtained at the same time was markedly elevated at >700 ng/mL (normal, <11.5 ng/mL), although this information was not available until several days later.

The patient underwent 2 additional surgeries during the same admission, including the prosthesis removal and tobramycin cement spacer placement, without incident. She was discharged home, again without incident. The patient was later evaluated by an outside allergist and underwent skin puncture and intradermal allergy testing. The results were consistent with a strong IgE-mediated hypersensitivity. Interestingly, she was found not to have a penicillin allergy.

Discussion

Vancomycin hypersensitivity reactions include the anaphylactoid reaction red man syndrome and a true IgE-mediated anaphylactic reaction. Red man syndrome is much more common, with reported rates in infected patients from 3.7% to 47%,^4,5 when vancomycin is given at the suggested  rate of 1 g over 1 hour. The reaction occurs because of histamine release from mast cells and basophils, and does not require previous sensitization.³ The rate of infusion is directly related to the development of symptoms, with 100% of patients developing symptoms in 1 study with rapid infusion (1 g over 10 min).⁶ Red man syndrome can typically be prevented by slowing the rate of infusion or by giving an H₁ blocker.³ Anaphylaxis is more rare but can occur.⁷ Anaphylaxis is mediated by vancomycin-specific IgE, which requires previous exposure, as was the case with our patient. Interestingly, the patient had received vancomycin many times without any signs of a hypersensitivity reaction. Antihistamines are not effective in treating anaphylaxis, and epinephrine is the first-line agent.³ This was clearly demonstrated in this case, as there was a significant hemodynamic response to epinephrine and a negligible response to other vasopressors, specifically norepinephrine and vasopressin.

Most hypersensitivity reactions during the course of a surgical procedure occur with induction of anesthesia, with neuromuscular blocking agents and antibiotics being the most common causes.⁸ In our case, antibiotics were held until after deep cultures were taken. Given the time from induction to the anaphylactic reaction, it is unlikely the reaction resulted from the induction agents or the neuromuscular blocking agent. The possibility of a transfusion reaction was also investigated, since a unit of pRBC was still being transfused when symptoms began. An acute hemolytic transfusion reaction has the classic triad of fever, flank pain, and hemoglobinuria, and can also present as DIC.⁹ Under anesthesia, DIC can often be the presenting sign. In this case, a hemolytic transfusion reaction appeared very unlikely. All of the blood components the patient received were rechecked and found to be compatible, posttransfusion analysis showed no evidence of hemolysis in any sample, and the direct antiglobulin test was negative in all components.

To our knowledge, there are no reported cases of vancomycin-induced anaphylaxis with concomitant DIC. Symptoms of anaphylaxis after exposure to a possible antigen include rapid onset of hypotension or rapid onset of signs in at least 2 organ systems, including cutaneous, gastrointestinal, respiratory, and cardiovascular.¹⁰ Anaphylaxis with DIC is rare after exposure to any substance but has been reported.¹¹ In fact, induction of systemic anaphylaxis in mice is known to cause DIC, with platelet-activating factor suggested as an important common mediator. A similar mechanism is suspected in humans.¹²

Confirmation of, and, certainly, prediction of, a vancomycin hypersensitivity reaction is difficult. Histamine levels can be used as a measure of mast-cell degranulation, but serum levels peak within 5 minutes and quickly return to baseline, limiting its diagnostic usefulness.³ Tryptase is an enzyme found in the secretory granules of mast cells. It has become an accepted marker of acute anaphylaxis, and, in vancomycin hypersensitivity reactions, can also distinguish between anaphylactic and anaphylactoid reactions.¹³ Tryptase levels peak 1 to 2 hours after the reaction, making this easier to measure than histamine, but results may not be available for several days, making it useful only in retrospect, as in our case. Skin testing is probably the best way to confirm a hypersensitivity reaction, although even this has been questioned with vancomycin because some find a high false-positive rate³, while others think the false-negative rate is likely too high.⁷ In this case, we were able to confirm our initial clinical suspicion with both an elevated tryptase level and a positive skin test.

Conclusion

We present a rare case of vancomycin anaphylaxis with DIC after repeated and prolonged previous exposure, which was treated acutely with hemodynamic resuscitation, replacement of blood components, steroids, and, most importantly, repeated boluses of epinephrine. Although several papers have described successful vancomycin desensitization⁷, this was fortunately not necessary in this case because the causative organism was sensitive to other acceptable antibiotics. The patient has been treated with systemic daptomycin and a tobramycin cement spacer without further incident.

Vancomycin is a glycopeptide antibiotic that exhibits bactericidal activity against gram-positive cocci. It is commonly recommended for surgical prophylaxis in cases of suspected bacterial resistance or penicillin allergy.¹ Two main types of hypersensitivity reactions associated with vancomycin can have similar presentations. Red man syndrome is an anaphylactoid reaction caused by direct release of histamine from mast cells via a nonimmunologic mechanism, and is the more common of the 2 reactions. The second type is an anaphylactic reaction, which is an immunoglobulin E (IgE)–mediated systemic event and requires exposure to become sensitized.^2,3

We present a patient who had received vancomycin on at least 12 occasions without incident. On this occasion, however, she developed a true anaphylactic reaction causing acute hemodynamic collapse that she survived after extensive resuscitation. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 55-year-old woman had a history of metastatic giant cell tumor of the right proximal tibia. She was originally treated 27 years ago for proximal tibial resection and reconstruction with a custom proximal tibial prosthesis. Four months later, she underwent resection of multiple pulmonary metastases via bilateral thoracotomies in a single surgical setting. After this, the patient had no evidence of recurrent metastatic disease. In subsequent years, the patient underwent multiple revision surgeries for problems such as hardware failure, patellar maltracking, and infection. The patient underwent 19 operations, including several nonorthopedic procedures. Because the patient had a rash after receiving penicillin as a child, she was thought to be allergic to penicillin. Consequently, she received vancomycin as antibiotic prophylaxis for the majority of these procedures. She also received extended courses of vancomycin of at least 6 weeks on 2 separate occasions. During her most recent revision procedure, 6 weeks prior to the procedure under discussion, the patient took vancomycin without incident. She was then found to have a prosthetic infection with Staphylococcus epidermidis, the same organism isolated in her previous infections, and she was advised to undergo a staged revision.

After a preoperative medical evaluation by her primary care physician, the patient was taken to the operating room for prosthesis removal and antibiotic spacer placement. She was anemic with a hemoglobin level of 8.8 g/dL; her erythrocyte sedimentation rate (ESR) was 102 mm/h (normal, <22 mm/h) and her C-reactive protein (CRP) was 38 mg/L (normal, <3 mg/L), but, otherwise, her laboratory values were normal, including a white blood cell count (WBC) of 8100/µL. Her electrocardiogram showed a normal sinus rhythm with nonspecific ST- and T-wave changes. Antibiotics were held until after cultures were taken. General endotracheal tube anesthesia was induced with 2 mg midazolam, 100 µg fentanyl, 180 mg propofol, and 140 mg succinylcholine, followed by 10 mg vecuronium, and maintained with desflurane. A tourniquet was not used per the surgeon’s routine. Dissection was carried down to the prosthesis and showed a small amount of purulent fluid. Transfusion of 1 unit of packed red blood cells (pRBC) was started during the approach owing to relatively low preoperative hemoglobin and significant blood loss. Approximately 500 mL of blood was lost during the approach secondary to the extensive dissection and the local inflammatory response from infection and recent surgery. After cultures were taken, and approximately 10 minutes after blood transfusion began, infusion of 1 g vancomycin in 250 mL normal saline was started via an infusion pump to run over 1 hour.

After infusion of 5 mL vancomycin, the patient’s blood pressure dropped from 117/63 mm Hg to 63/30 mm Hg; her pulse concurrently dropped from 90 to 50 beats/min. Vancomycin infusion was immediately stopped, anesthesia gasses were turned off, and patient received a bolus of normal saline with a second unit of pRBC. Patient received boluses of 0.5 mg to 1.0 mg epinephrine and 100 µg phenylephrine without sustained increase in blood pressure, which had dropped to 54/24 mm Hg, although the patient became tachycardic to ~120 beats/min after epinephrine. A sudden drop in end-tidal CO₂ from 40s mm Hg to 20s mm Hg was also noted, indicating continuous but significantly decreased perfusion of the lungs.

We elected to abort the procedure, and a vacuum-assisted closure (VAC) dressing was applied to the open wound. After 15 minutes, the patient’s pulses, which had been faint, became impalpable, and cardiopulmonary resuscitation was initiated for about 7 minutes. The patient received 40 units vasopressin with repeated boluses of 0.5 mg epinephrine; a norepinephrine continuous infusion was started with the return of pulses. The patient also received 50 mg diphenhydramine, 125 mg methylprednisolone, and 20 mg famotidine for suspected anaphylaxis. A central venous line and arterial line were placed, and blood was drawn for laboratory analysis. The patient was noted to have clear breath sounds with no obvious rash, and her urine remained clear. Blood gas showed a profound metabolic acidosis, with pH of 7.09, base deficit of 5.9, and lactate of 8.9. The patient was treated with bicarbonate infusion. The patient was noted to ooze significantly during central venous line and arterial line placement, despite apparently normal coagulation during the surgical approach. Coagulation values were consistent with disseminated intravascular coagulation (DIC): prothrombin time, 57 s (international normalized ratio, 6.7); partial thromboplastin time, >200 s; thrombin time, 110 s; D-dimer, >10,000 ng/mL (normal, 0-200 ng/mL); and fibrinogen, <60 mg/dL (normal, 222-475 mg/dL). The patient’s thromboelastogram showed a flat line indicating an absence of clotting. Interestingly, the platelet count remained near the preoperative level at 338×10³/µL. The patient’s blood pressure remained labile and was responsive primarily to epinephrine boluses, of which she received a total of 5 mg. After 1 hour of resuscitation, during which time the patient received a total of 5 L crystalloid and 3 units pRBC, the patient was transferred to the intensive care unit (ICU), intubated, and started on a titrated epinephrine infusion.

Upon arrival in the ICU, the patient quickly stabilized hemodynamically. She was weaned from all inotropic support within 2 hours of arrival. The patient lost 800 mL of blood through wound VAC over the first 12 hours postoperatively and required a total of 11 units of pRBC, 6 units fresh frozen plasma, and 3 units of pooled cryoprecipitate, all of which were compatible. Laboratory values, including arterial pH, lactic acid, and coagulation studies, normalized on the evening of surgery, and, by the next morning, the patient was alert and was extubated without difficulty. Steroids were tapered without hemodynamic compromise while the patient was in the ICU. Cardiology examination revealed no abnormalities. Because of the temporal association of blood transfusion with cardiovascular collapse, pRBC units were retested for antibodies and cultured. Both of these investigations were negative. Wound cultures again were positive for Staphylococcus epidermidis, and blood cultures were negative. The patient was started on daptomycin based on susceptibility profiles. Serum histamine levels taken during initial resuscitation in the operating room were normal. The serum tryptase level obtained at the same time was markedly elevated at >700 ng/mL (normal, <11.5 ng/mL), although this information was not available until several days later.

The patient underwent 2 additional surgeries during the same admission, including the prosthesis removal and tobramycin cement spacer placement, without incident. She was discharged home, again without incident. The patient was later evaluated by an outside allergist and underwent skin puncture and intradermal allergy testing. The results were consistent with a strong IgE-mediated hypersensitivity. Interestingly, she was found not to have a penicillin allergy.

Discussion

Vancomycin hypersensitivity reactions include the anaphylactoid reaction red man syndrome and a true IgE-mediated anaphylactic reaction. Red man syndrome is much more common, with reported rates in infected patients from 3.7% to 47%,^4,5 when vancomycin is given at the suggested  rate of 1 g over 1 hour. The reaction occurs because of histamine release from mast cells and basophils, and does not require previous sensitization.³ The rate of infusion is directly related to the development of symptoms, with 100% of patients developing symptoms in 1 study with rapid infusion (1 g over 10 min).⁶ Red man syndrome can typically be prevented by slowing the rate of infusion or by giving an H₁ blocker.³ Anaphylaxis is more rare but can occur.⁷ Anaphylaxis is mediated by vancomycin-specific IgE, which requires previous exposure, as was the case with our patient. Interestingly, the patient had received vancomycin many times without any signs of a hypersensitivity reaction. Antihistamines are not effective in treating anaphylaxis, and epinephrine is the first-line agent.³ This was clearly demonstrated in this case, as there was a significant hemodynamic response to epinephrine and a negligible response to other vasopressors, specifically norepinephrine and vasopressin.

Most hypersensitivity reactions during the course of a surgical procedure occur with induction of anesthesia, with neuromuscular blocking agents and antibiotics being the most common causes.⁸ In our case, antibiotics were held until after deep cultures were taken. Given the time from induction to the anaphylactic reaction, it is unlikely the reaction resulted from the induction agents or the neuromuscular blocking agent. The possibility of a transfusion reaction was also investigated, since a unit of pRBC was still being transfused when symptoms began. An acute hemolytic transfusion reaction has the classic triad of fever, flank pain, and hemoglobinuria, and can also present as DIC.⁹ Under anesthesia, DIC can often be the presenting sign. In this case, a hemolytic transfusion reaction appeared very unlikely. All of the blood components the patient received were rechecked and found to be compatible, posttransfusion analysis showed no evidence of hemolysis in any sample, and the direct antiglobulin test was negative in all components.

To our knowledge, there are no reported cases of vancomycin-induced anaphylaxis with concomitant DIC. Symptoms of anaphylaxis after exposure to a possible antigen include rapid onset of hypotension or rapid onset of signs in at least 2 organ systems, including cutaneous, gastrointestinal, respiratory, and cardiovascular.¹⁰ Anaphylaxis with DIC is rare after exposure to any substance but has been reported.¹¹ In fact, induction of systemic anaphylaxis in mice is known to cause DIC, with platelet-activating factor suggested as an important common mediator. A similar mechanism is suspected in humans.¹²

Confirmation of, and, certainly, prediction of, a vancomycin hypersensitivity reaction is difficult. Histamine levels can be used as a measure of mast-cell degranulation, but serum levels peak within 5 minutes and quickly return to baseline, limiting its diagnostic usefulness.³ Tryptase is an enzyme found in the secretory granules of mast cells. It has become an accepted marker of acute anaphylaxis, and, in vancomycin hypersensitivity reactions, can also distinguish between anaphylactic and anaphylactoid reactions.¹³ Tryptase levels peak 1 to 2 hours after the reaction, making this easier to measure than histamine, but results may not be available for several days, making it useful only in retrospect, as in our case. Skin testing is probably the best way to confirm a hypersensitivity reaction, although even this has been questioned with vancomycin because some find a high false-positive rate³, while others think the false-negative rate is likely too high.⁷ In this case, we were able to confirm our initial clinical suspicion with both an elevated tryptase level and a positive skin test.

Conclusion

We present a rare case of vancomycin anaphylaxis with DIC after repeated and prolonged previous exposure, which was treated acutely with hemodynamic resuscitation, replacement of blood components, steroids, and, most importantly, repeated boluses of epinephrine. Although several papers have described successful vancomycin desensitization⁷, this was fortunately not necessary in this case because the causative organism was sensitive to other acceptable antibiotics. The patient has been treated with systemic daptomycin and a tobramycin cement spacer without further incident.

Necrotizing fasciitis (NF) is a severe, rapidly spreading soft-tissue infection with high morbidity and mortality. Bacteriology in NF may be varied, and the etiology is often polymicrobial. It is important to consider the potential for fungal involvement despite its rarity. Cryptococcal NF has been reported in immunocompromised patients, with Cryptococcus neoformans being the most common offending organism.^1-4

C neoformans is a basidiomycotic yeast that was previously considered a homogenous species.^5,6 From the antigenic properties of its polysaccharide capsule, 3 main variants were described: C neoformans var. grubii, C neoformans var. neoformans, and C neoformans var. gattii. Subsequently, C neoformans var. gattii was found to be genetically and biochemically different from C neoformans. This discovery led to the distinction of C neoformans var. gattii as a separate species and it being renamed C gattii.⁶

C gattii was first recognized on Vancouver Island in 2001.⁷ Although C gattii is predominantly restricted to tropical and subtropical climates, its true epidemiology has been limited by diagnostic methods. C gattii can be diagnosed with laboratory culture media such as birdseed agars and L-canavanine-glycine-bromothymol (CGB) agar.⁶ However, most reports of Cryptococcus NF do not specify the culture media used to isolate Cryptococcus. In addition to culture media, molecular genotyping studies also allow for confirmation of the diagnosis of C gattii and have the added benefit of enabling identification of the molecular genotype. Nonetheless, in many clinical microbiology laboratories, Cryptococcus is not identified to the species level, much less to the molecular genotype.⁷ Given these diagnostic limitations and the fact that C gattii was only recently identified as a separate species, it is possible that any pre-2006 cases of NF attributed to C neoformans could in fact have been caused by C gattii.

In this article, we review the literature and report a case of NF of the hand that was caused by C gattii in a patient with diabetes. To our knowledge, this is the first reported case of NF caused by C gattii. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 73-year-old man was admitted with a 1-week history of swelling and pain in the dorsum of the left hand. He had been sitting in an outdoor eatery in Singapore when an insect bit the hand over the dorsum. Two days later, he consulted his family physician, who began treatment with oral amoxicillin/clavulanic acid. After 4 days of treatment, there was clinical progression of increased swelling and pain in the hand. Six days after initial injury, the patient presented to the department of orthopedic surgery.

Physical examination revealed diffuse, brawny, nonfluctuant swelling over the entire dorsum of the left hand (Figure 1). There was a 1×1-cm ruptured blister with some nonpurulent discharge just distal to the wrist joint. Neurovascular status and the extensor mechanism of the fingers were intact. The wrist joint had full range of motion. There was no fever.

Laboratory testing revealed an elevated white blood cell count (16.6×10⁹/L), a C-reactive protein (CRP) level of 237 nmol/L, a random blood glucose level of 12.6 mmol/L, and a LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score of 7.⁸

Given the severe swelling, intravenous amoxicillin/clavulanic acid was started. The patient received a total of 3 doses before operative débridement of the left hand. Operative findings were NF of the hand, grayish necrotic fascia, and foul-smelling “dishwater” fluid. A single specimen of fascia from the surgical site was sent for examination. Histopathologic examination of formalin-fixed, paraffin-embedded tissue revealed necrotizing suppurative inflammation with fungal organisms present (Figures 2, 3).

Tissue cultures were obtained during surgery. The organism grew as scanty, small, wet-looking colonies on sheep blood agar after 48 hours of incubation. Microscopy revealed an oval yeast. The organism was identified and reported as C gattii by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS; Biotyper 2.0.1 software; Bruker Daltonics), with a score of 1.914.⁹ All other intraoperative cultures for aerobic and anaerobic bacteria were negative. Molecular genotyping was performed with polymerase chain reaction assay to identify the molecular subtype.¹⁰C gattii genotype VGII was isolated. A cryptococcal serum antigen assay was positive at 1:256.

A series of tests was performed to screen for disseminated disease. Blood cultures were negative for fungus. Chest radiography and computed tomography of the brain did not show any pulmonary or cerebral involvement. Cerebrospinal fluid was not available for examination, as the patient declined lumbar puncture. Blood tests included a negative result for human immunodeficiency virus (HIV). The patient was found to have previously undiagnosed diabetes mellitus (hemoglobin A_1c, 7.9%). T-cell counts and ratios were normal.

The patient was started on intravenous amphotericin B 60 mg/d and flucytosine 500 mg every 6 hours for 3 weeks. Oral fluconazole 400 mg every morning was also given (intended duration, 6 mo). Given that diabetes was newly diagnosed, the patient was treated with metformin; his capillary blood glucose level remained stable during his inpatient stay.

Four débridements of the dorsal hand wound were performed—the first on day of admission and the other 3 on hospitalization days 3, 7, and 18 (Figure 4). Subsequent wound resurfacing with a split skin graft harvested from the forearm was performed on hospitalization day 22. After surgery, the hand was dressed with a bulky cotton dressing. Five days after the patient was discharged, during review in the outpatient clinic, the skin graft was noted to be taking well. The patient did not attend postoperative physical therapy. He was maintained on metformin and given a follow-up clinic appointment for his diabetes. Four months after surgery, the wound was completely healed, and normal functional use of the hand recovered.

Discussion

NF is a severe soft-tissue infection with potential for rapid progression. Surgical débridement should be performed urgently to reduce the chance of morbidity and mortality.¹¹ The initial classification by Giuliano and colleagues¹² was based on bacteriology and included type I (anaerobic species in combination with a facultative species) and type II (monomicrobial usually involving group A β-hemolytic Streptococcus). This classification was modified by Morgan¹³ to include gram-negative organisms as well as fungal organisms (Table 1).

Fungal NF is rare, with Candida, Apophysomyces, and Cryptococcus described in the literature.^1,14,15 Fungal infections tend to occur in immunocompromised patients; risk factors are steroid immunosuppression, poorly controlled diabetes, and peripheral vascular disease.¹⁶ Some zygomycetes may also affect immunocompetent patients.¹⁵

C gattii is an encapsulated yeast organism that is genetically and biochemically distinct from C neoformans. It is endemic to tropical parts of Africa and Australia. Its main environmental sources are eucalyptus trees (Eucalyptus camaldulensis, Eucalyptus tereticornis) and decaying hollows in living trees.¹⁷ In addition, there have been reports of isolation of C gattii from insect frass,¹⁸ which would make infection by an insect bite a possible transmission route. Worldwide distribution of this pathogen has increased recently, with outbreaks noted on Vancouver Island and in areas in Canada and the northwest United States.⁷

The true incidence of NF secondary to C gattii is difficult to determine. C gattii was only recently identified as a separate species, and pre-2006 cases of NF attributed to C neoformans may instead have been caused by C gattii. Misidentification has been compounded by the fact that the tests required for accurate diagnosis of C gattii infection may not be readily available in many clinical microbiology laboratories. Cryptococcus can be identified with various methods, including direct microscopy, culturing of tissue or fluid samples, and measurement of cryptococcal serum antigen. However, tests such as specific culture media, mass spectrometry, and molecular typing studies are required to determine cryptococcal species. L-canavanine-glycine-bromothymol blue (CGB) agar is a medium that is often used to differentiate C gattii from C neoformans because of the ability of C gattii to produce a blue appearance.⁶ Modern techniques, such as MALDI-TOF MS, have also been used to successfully distinguish between C gattii and C neoformans.⁹ MALDI-TOF MS identifies species on the basis of characteristic protein spectra extracted from whole cells. Using commercial and supplemental reference libraries, the system compares signal matches in the reference spectrum with Cryptococcus entries in the library—allowing rapid and accurate identification of cryptococcal species. However, this diagnostic method is limited by availability of adequate Cryptococcus entries in the reference library and by the high cost of acquiring the machine.

Serotyping is based on the antigenic property of the capsule and was once used to differentiate C neoformans into its 3 main varieties: var. neoformans, var. grubii, var. gattii. However, when it was realized that the antigenic property of the strain can be unstable and that there are hybrids containing more than 1 serotype, serotyping was abandoned as a species-differentiation test.⁶ The current gold standard for species differentiation is molecular genotyping. Molecular genotyping studies can confirm the diagnosis of C gattii infection and allow differentiation of C gattii into its 4 main molecular types: VGI, VGII, VGIII, VGIV. Using methods such as polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis, molecular typing allows for specific epidemiology charting of C gattii genotypes.⁷

Although the transmission route for cryptococcal infection is mainly respiratory, direct inoculation has been reported as well.¹⁹ Cutaneous lesions, which occur in 5% to 20% of cryptococcal infections, often present in the head and neck.^2,20,21 Primary cutaneous infections from cryptococcosis are rare, and cutaneous manifestations are often a sign of disseminated disease. Disseminated disease is defined as the involvement of 2 or more noncontiguous sites or evidence of high fungal burden based on cryptococcal antigen titer of more than 1:512.¹² It is important to exclude disseminated disease in all cases of cryptococcosis, as it may be fatal.²⁰ The neural and pulmonary systems should be screened.²² Cellulitis from cryptococcosis is almost always limited to immunocompromised patients, though there are reports of crytococcal cutaneous disease in immunocompetent patients.^3,15 Interestingly, though C neoformans often affects immunocompromised patients, the emerging pathogen of C gattii affects immunocompetent patients.^7,17,23 Our patient’s undiagnosed diabetes may have been a risk factor for cryptococcal infection. His cryptococcal antigen titer was 1:256, with no evidence of other sites of involvement. We therefore believe this to be a rare case of direct inoculation secondary to an insect bite.

The literature includes 12 reported cases of NF secondary to Cryptococcus (Table 2), all C neoformans. Of these cases, 9 involved immunosuppression, and most of these patients were on long-term steroid treatment after organ transplantation. The most common infection site was the lower extremity. These cases of cryptococcal NF show that immunosuppression, and long-term steroid use in particular, is an important risk factor. The mortality rate for these reviewed cases was 41.6% (5/12). According to the literature, the mortality rates for patients with cryptococcal soft-tissue infections²⁴ and posttransplant patients with cryptococcal NF²¹ were 37.5% and 60%, respectively. We believe the mortality rate in our reviewed cases likely was confounded by the fact that most of the patients were posttransplant patients on long-term immunosuppression.

Of the 12 patients, 5 had primary cutaneous disease. There seems to be no relationship between outcome and dissemination of disease. In addition, there is a paucity of literature on the effect of disseminated disease and cryptococcal soft-tissue infections. Therefore, no firm conclusions can be drawn regarding the effects of disseminated disease on severity of cryptococcal soft-tissue infection.

Treatment of cryptococcal NF involves a combination of surgical débridement and long-term antifungal therapy. Surgical débridement of NF includes delineating the extent of infection with complete surgical excision of the affected tissue.²⁵ The aims of surgery should be to remove all unhealthy tissue, identify the offending organism, and plan for resurfacing or reconstruction of the afflicted extremity. Intraoperative-tissue histology should be performed to confirm the diagnosis of NF. Histology can be used to demonstrate cryptococcal infection. The diagnosis of cryptococcal infection can be aided with fungal cultures, and therefore we recommend that tissue cultures be sent not only for routine aerobic/anaerobic bacteria but also for mycobacteria and fungal organisms. Laboratory tests that aid in diagnosis include serum cryptococcal antigen titer.

The current treatment recommendation for cryptococcal disease in patients who are not HIV-positive or transplant hosts is amphotericin B deoxycholate 0.7 to 1.0 mg/kg/d plus flucytosine 100 mg/kg/d for at least 4 weeks.²² The regimen period may be shortened to 14 days for patients at low risk of treatment failure. Fluconazole should be given as maintenance therapy (200 mg/d) for 6 to 12 months. There is no compelling evidence for immunoglobulin therapy for cryptococcal disease.²²

Conclusion

NF caused by Cryptococcus is rare. A high level of suspicion, and intraoperative specimens for histology and fungal microscopy and culture, can help in establishing the diagnosis. Molecular genotyping remains the diagnostic method of choice for NF secondary to Cryptococcus. Effective treatment consists of aggressive surgical débridement and antifungal therapy.

Necrotizing fasciitis (NF) is a severe, rapidly spreading soft-tissue infection with high morbidity and mortality. Bacteriology in NF may be varied, and the etiology is often polymicrobial. It is important to consider the potential for fungal involvement despite its rarity. Cryptococcal NF has been reported in immunocompromised patients, with Cryptococcus neoformans being the most common offending organism.^1-4

C neoformans is a basidiomycotic yeast that was previously considered a homogenous species.^5,6 From the antigenic properties of its polysaccharide capsule, 3 main variants were described: C neoformans var. grubii, C neoformans var. neoformans, and C neoformans var. gattii. Subsequently, C neoformans var. gattii was found to be genetically and biochemically different from C neoformans. This discovery led to the distinction of C neoformans var. gattii as a separate species and it being renamed C gattii.⁶

C gattii was first recognized on Vancouver Island in 2001.⁷ Although C gattii is predominantly restricted to tropical and subtropical climates, its true epidemiology has been limited by diagnostic methods. C gattii can be diagnosed with laboratory culture media such as birdseed agars and L-canavanine-glycine-bromothymol (CGB) agar.⁶ However, most reports of Cryptococcus NF do not specify the culture media used to isolate Cryptococcus. In addition to culture media, molecular genotyping studies also allow for confirmation of the diagnosis of C gattii and have the added benefit of enabling identification of the molecular genotype. Nonetheless, in many clinical microbiology laboratories, Cryptococcus is not identified to the species level, much less to the molecular genotype.⁷ Given these diagnostic limitations and the fact that C gattii was only recently identified as a separate species, it is possible that any pre-2006 cases of NF attributed to C neoformans could in fact have been caused by C gattii.

In this article, we review the literature and report a case of NF of the hand that was caused by C gattii in a patient with diabetes. To our knowledge, this is the first reported case of NF caused by C gattii. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 73-year-old man was admitted with a 1-week history of swelling and pain in the dorsum of the left hand. He had been sitting in an outdoor eatery in Singapore when an insect bit the hand over the dorsum. Two days later, he consulted his family physician, who began treatment with oral amoxicillin/clavulanic acid. After 4 days of treatment, there was clinical progression of increased swelling and pain in the hand. Six days after initial injury, the patient presented to the department of orthopedic surgery.

Physical examination revealed diffuse, brawny, nonfluctuant swelling over the entire dorsum of the left hand (Figure 1). There was a 1×1-cm ruptured blister with some nonpurulent discharge just distal to the wrist joint. Neurovascular status and the extensor mechanism of the fingers were intact. The wrist joint had full range of motion. There was no fever.

Laboratory testing revealed an elevated white blood cell count (16.6×10⁹/L), a C-reactive protein (CRP) level of 237 nmol/L, a random blood glucose level of 12.6 mmol/L, and a LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score of 7.⁸

Given the severe swelling, intravenous amoxicillin/clavulanic acid was started. The patient received a total of 3 doses before operative débridement of the left hand. Operative findings were NF of the hand, grayish necrotic fascia, and foul-smelling “dishwater” fluid. A single specimen of fascia from the surgical site was sent for examination. Histopathologic examination of formalin-fixed, paraffin-embedded tissue revealed necrotizing suppurative inflammation with fungal organisms present (Figures 2, 3).

Tissue cultures were obtained during surgery. The organism grew as scanty, small, wet-looking colonies on sheep blood agar after 48 hours of incubation. Microscopy revealed an oval yeast. The organism was identified and reported as C gattii by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS; Biotyper 2.0.1 software; Bruker Daltonics), with a score of 1.914.⁹ All other intraoperative cultures for aerobic and anaerobic bacteria were negative. Molecular genotyping was performed with polymerase chain reaction assay to identify the molecular subtype.¹⁰C gattii genotype VGII was isolated. A cryptococcal serum antigen assay was positive at 1:256.

A series of tests was performed to screen for disseminated disease. Blood cultures were negative for fungus. Chest radiography and computed tomography of the brain did not show any pulmonary or cerebral involvement. Cerebrospinal fluid was not available for examination, as the patient declined lumbar puncture. Blood tests included a negative result for human immunodeficiency virus (HIV). The patient was found to have previously undiagnosed diabetes mellitus (hemoglobin A_1c, 7.9%). T-cell counts and ratios were normal.

The patient was started on intravenous amphotericin B 60 mg/d and flucytosine 500 mg every 6 hours for 3 weeks. Oral fluconazole 400 mg every morning was also given (intended duration, 6 mo). Given that diabetes was newly diagnosed, the patient was treated with metformin; his capillary blood glucose level remained stable during his inpatient stay.

Four débridements of the dorsal hand wound were performed—the first on day of admission and the other 3 on hospitalization days 3, 7, and 18 (Figure 4). Subsequent wound resurfacing with a split skin graft harvested from the forearm was performed on hospitalization day 22. After surgery, the hand was dressed with a bulky cotton dressing. Five days after the patient was discharged, during review in the outpatient clinic, the skin graft was noted to be taking well. The patient did not attend postoperative physical therapy. He was maintained on metformin and given a follow-up clinic appointment for his diabetes. Four months after surgery, the wound was completely healed, and normal functional use of the hand recovered.

Discussion

NF is a severe soft-tissue infection with potential for rapid progression. Surgical débridement should be performed urgently to reduce the chance of morbidity and mortality.¹¹ The initial classification by Giuliano and colleagues¹² was based on bacteriology and included type I (anaerobic species in combination with a facultative species) and type II (monomicrobial usually involving group A β-hemolytic Streptococcus). This classification was modified by Morgan¹³ to include gram-negative organisms as well as fungal organisms (Table 1).

Fungal NF is rare, with Candida, Apophysomyces, and Cryptococcus described in the literature.^1,14,15 Fungal infections tend to occur in immunocompromised patients; risk factors are steroid immunosuppression, poorly controlled diabetes, and peripheral vascular disease.¹⁶ Some zygomycetes may also affect immunocompetent patients.¹⁵

C gattii is an encapsulated yeast organism that is genetically and biochemically distinct from C neoformans. It is endemic to tropical parts of Africa and Australia. Its main environmental sources are eucalyptus trees (Eucalyptus camaldulensis, Eucalyptus tereticornis) and decaying hollows in living trees.¹⁷ In addition, there have been reports of isolation of C gattii from insect frass,¹⁸ which would make infection by an insect bite a possible transmission route. Worldwide distribution of this pathogen has increased recently, with outbreaks noted on Vancouver Island and in areas in Canada and the northwest United States.⁷

The true incidence of NF secondary to C gattii is difficult to determine. C gattii was only recently identified as a separate species, and pre-2006 cases of NF attributed to C neoformans may instead have been caused by C gattii. Misidentification has been compounded by the fact that the tests required for accurate diagnosis of C gattii infection may not be readily available in many clinical microbiology laboratories. Cryptococcus can be identified with various methods, including direct microscopy, culturing of tissue or fluid samples, and measurement of cryptococcal serum antigen. However, tests such as specific culture media, mass spectrometry, and molecular typing studies are required to determine cryptococcal species. L-canavanine-glycine-bromothymol blue (CGB) agar is a medium that is often used to differentiate C gattii from C neoformans because of the ability of C gattii to produce a blue appearance.⁶ Modern techniques, such as MALDI-TOF MS, have also been used to successfully distinguish between C gattii and C neoformans.⁹ MALDI-TOF MS identifies species on the basis of characteristic protein spectra extracted from whole cells. Using commercial and supplemental reference libraries, the system compares signal matches in the reference spectrum with Cryptococcus entries in the library—allowing rapid and accurate identification of cryptococcal species. However, this diagnostic method is limited by availability of adequate Cryptococcus entries in the reference library and by the high cost of acquiring the machine.

Serotyping is based on the antigenic property of the capsule and was once used to differentiate C neoformans into its 3 main varieties: var. neoformans, var. grubii, var. gattii. However, when it was realized that the antigenic property of the strain can be unstable and that there are hybrids containing more than 1 serotype, serotyping was abandoned as a species-differentiation test.⁶ The current gold standard for species differentiation is molecular genotyping. Molecular genotyping studies can confirm the diagnosis of C gattii infection and allow differentiation of C gattii into its 4 main molecular types: VGI, VGII, VGIII, VGIV. Using methods such as polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis, molecular typing allows for specific epidemiology charting of C gattii genotypes.⁷

Although the transmission route for cryptococcal infection is mainly respiratory, direct inoculation has been reported as well.¹⁹ Cutaneous lesions, which occur in 5% to 20% of cryptococcal infections, often present in the head and neck.^2,20,21 Primary cutaneous infections from cryptococcosis are rare, and cutaneous manifestations are often a sign of disseminated disease. Disseminated disease is defined as the involvement of 2 or more noncontiguous sites or evidence of high fungal burden based on cryptococcal antigen titer of more than 1:512.¹² It is important to exclude disseminated disease in all cases of cryptococcosis, as it may be fatal.²⁰ The neural and pulmonary systems should be screened.²² Cellulitis from cryptococcosis is almost always limited to immunocompromised patients, though there are reports of crytococcal cutaneous disease in immunocompetent patients.^3,15 Interestingly, though C neoformans often affects immunocompromised patients, the emerging pathogen of C gattii affects immunocompetent patients.^7,17,23 Our patient’s undiagnosed diabetes may have been a risk factor for cryptococcal infection. His cryptococcal antigen titer was 1:256, with no evidence of other sites of involvement. We therefore believe this to be a rare case of direct inoculation secondary to an insect bite.

The literature includes 12 reported cases of NF secondary to Cryptococcus (Table 2), all C neoformans. Of these cases, 9 involved immunosuppression, and most of these patients were on long-term steroid treatment after organ transplantation. The most common infection site was the lower extremity. These cases of cryptococcal NF show that immunosuppression, and long-term steroid use in particular, is an important risk factor. The mortality rate for these reviewed cases was 41.6% (5/12). According to the literature, the mortality rates for patients with cryptococcal soft-tissue infections²⁴ and posttransplant patients with cryptococcal NF²¹ were 37.5% and 60%, respectively. We believe the mortality rate in our reviewed cases likely was confounded by the fact that most of the patients were posttransplant patients on long-term immunosuppression.

Of the 12 patients, 5 had primary cutaneous disease. There seems to be no relationship between outcome and dissemination of disease. In addition, there is a paucity of literature on the effect of disseminated disease and cryptococcal soft-tissue infections. Therefore, no firm conclusions can be drawn regarding the effects of disseminated disease on severity of cryptococcal soft-tissue infection.

Treatment of cryptococcal NF involves a combination of surgical débridement and long-term antifungal therapy. Surgical débridement of NF includes delineating the extent of infection with complete surgical excision of the affected tissue.²⁵ The aims of surgery should be to remove all unhealthy tissue, identify the offending organism, and plan for resurfacing or reconstruction of the afflicted extremity. Intraoperative-tissue histology should be performed to confirm the diagnosis of NF. Histology can be used to demonstrate cryptococcal infection. The diagnosis of cryptococcal infection can be aided with fungal cultures, and therefore we recommend that tissue cultures be sent not only for routine aerobic/anaerobic bacteria but also for mycobacteria and fungal organisms. Laboratory tests that aid in diagnosis include serum cryptococcal antigen titer.

The current treatment recommendation for cryptococcal disease in patients who are not HIV-positive or transplant hosts is amphotericin B deoxycholate 0.7 to 1.0 mg/kg/d plus flucytosine 100 mg/kg/d for at least 4 weeks.²² The regimen period may be shortened to 14 days for patients at low risk of treatment failure. Fluconazole should be given as maintenance therapy (200 mg/d) for 6 to 12 months. There is no compelling evidence for immunoglobulin therapy for cryptococcal disease.²²

Conclusion

NF caused by Cryptococcus is rare. A high level of suspicion, and intraoperative specimens for histology and fungal microscopy and culture, can help in establishing the diagnosis. Molecular genotyping remains the diagnostic method of choice for NF secondary to Cryptococcus. Effective treatment consists of aggressive surgical débridement and antifungal therapy.

Necrotizing fasciitis (NF) is a severe, rapidly spreading soft-tissue infection with high morbidity and mortality. Bacteriology in NF may be varied, and the etiology is often polymicrobial. It is important to consider the potential for fungal involvement despite its rarity. Cryptococcal NF has been reported in immunocompromised patients, with Cryptococcus neoformans being the most common offending organism.^1-4

C neoformans is a basidiomycotic yeast that was previously considered a homogenous species.^5,6 From the antigenic properties of its polysaccharide capsule, 3 main variants were described: C neoformans var. grubii, C neoformans var. neoformans, and C neoformans var. gattii. Subsequently, C neoformans var. gattii was found to be genetically and biochemically different from C neoformans. This discovery led to the distinction of C neoformans var. gattii as a separate species and it being renamed C gattii.⁶

C gattii was first recognized on Vancouver Island in 2001.⁷ Although C gattii is predominantly restricted to tropical and subtropical climates, its true epidemiology has been limited by diagnostic methods. C gattii can be diagnosed with laboratory culture media such as birdseed agars and L-canavanine-glycine-bromothymol (CGB) agar.⁶ However, most reports of Cryptococcus NF do not specify the culture media used to isolate Cryptococcus. In addition to culture media, molecular genotyping studies also allow for confirmation of the diagnosis of C gattii and have the added benefit of enabling identification of the molecular genotype. Nonetheless, in many clinical microbiology laboratories, Cryptococcus is not identified to the species level, much less to the molecular genotype.⁷ Given these diagnostic limitations and the fact that C gattii was only recently identified as a separate species, it is possible that any pre-2006 cases of NF attributed to C neoformans could in fact have been caused by C gattii.

In this article, we review the literature and report a case of NF of the hand that was caused by C gattii in a patient with diabetes. To our knowledge, this is the first reported case of NF caused by C gattii. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 73-year-old man was admitted with a 1-week history of swelling and pain in the dorsum of the left hand. He had been sitting in an outdoor eatery in Singapore when an insect bit the hand over the dorsum. Two days later, he consulted his family physician, who began treatment with oral amoxicillin/clavulanic acid. After 4 days of treatment, there was clinical progression of increased swelling and pain in the hand. Six days after initial injury, the patient presented to the department of orthopedic surgery.

Physical examination revealed diffuse, brawny, nonfluctuant swelling over the entire dorsum of the left hand (Figure 1). There was a 1×1-cm ruptured blister with some nonpurulent discharge just distal to the wrist joint. Neurovascular status and the extensor mechanism of the fingers were intact. The wrist joint had full range of motion. There was no fever.

Laboratory testing revealed an elevated white blood cell count (16.6×10⁹/L), a C-reactive protein (CRP) level of 237 nmol/L, a random blood glucose level of 12.6 mmol/L, and a LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score of 7.⁸

Given the severe swelling, intravenous amoxicillin/clavulanic acid was started. The patient received a total of 3 doses before operative débridement of the left hand. Operative findings were NF of the hand, grayish necrotic fascia, and foul-smelling “dishwater” fluid. A single specimen of fascia from the surgical site was sent for examination. Histopathologic examination of formalin-fixed, paraffin-embedded tissue revealed necrotizing suppurative inflammation with fungal organisms present (Figures 2, 3).

Tissue cultures were obtained during surgery. The organism grew as scanty, small, wet-looking colonies on sheep blood agar after 48 hours of incubation. Microscopy revealed an oval yeast. The organism was identified and reported as C gattii by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS; Biotyper 2.0.1 software; Bruker Daltonics), with a score of 1.914.⁹ All other intraoperative cultures for aerobic and anaerobic bacteria were negative. Molecular genotyping was performed with polymerase chain reaction assay to identify the molecular subtype.¹⁰C gattii genotype VGII was isolated. A cryptococcal serum antigen assay was positive at 1:256.

A series of tests was performed to screen for disseminated disease. Blood cultures were negative for fungus. Chest radiography and computed tomography of the brain did not show any pulmonary or cerebral involvement. Cerebrospinal fluid was not available for examination, as the patient declined lumbar puncture. Blood tests included a negative result for human immunodeficiency virus (HIV). The patient was found to have previously undiagnosed diabetes mellitus (hemoglobin A_1c, 7.9%). T-cell counts and ratios were normal.

The patient was started on intravenous amphotericin B 60 mg/d and flucytosine 500 mg every 6 hours for 3 weeks. Oral fluconazole 400 mg every morning was also given (intended duration, 6 mo). Given that diabetes was newly diagnosed, the patient was treated with metformin; his capillary blood glucose level remained stable during his inpatient stay.

Four débridements of the dorsal hand wound were performed—the first on day of admission and the other 3 on hospitalization days 3, 7, and 18 (Figure 4). Subsequent wound resurfacing with a split skin graft harvested from the forearm was performed on hospitalization day 22. After surgery, the hand was dressed with a bulky cotton dressing. Five days after the patient was discharged, during review in the outpatient clinic, the skin graft was noted to be taking well. The patient did not attend postoperative physical therapy. He was maintained on metformin and given a follow-up clinic appointment for his diabetes. Four months after surgery, the wound was completely healed, and normal functional use of the hand recovered.

Discussion

NF is a severe soft-tissue infection with potential for rapid progression. Surgical débridement should be performed urgently to reduce the chance of morbidity and mortality.¹¹ The initial classification by Giuliano and colleagues¹² was based on bacteriology and included type I (anaerobic species in combination with a facultative species) and type II (monomicrobial usually involving group A β-hemolytic Streptococcus). This classification was modified by Morgan¹³ to include gram-negative organisms as well as fungal organisms (Table 1).

Fungal NF is rare, with Candida, Apophysomyces, and Cryptococcus described in the literature.^1,14,15 Fungal infections tend to occur in immunocompromised patients; risk factors are steroid immunosuppression, poorly controlled diabetes, and peripheral vascular disease.¹⁶ Some zygomycetes may also affect immunocompetent patients.¹⁵

C gattii is an encapsulated yeast organism that is genetically and biochemically distinct from C neoformans. It is endemic to tropical parts of Africa and Australia. Its main environmental sources are eucalyptus trees (Eucalyptus camaldulensis, Eucalyptus tereticornis) and decaying hollows in living trees.¹⁷ In addition, there have been reports of isolation of C gattii from insect frass,¹⁸ which would make infection by an insect bite a possible transmission route. Worldwide distribution of this pathogen has increased recently, with outbreaks noted on Vancouver Island and in areas in Canada and the northwest United States.⁷

The true incidence of NF secondary to C gattii is difficult to determine. C gattii was only recently identified as a separate species, and pre-2006 cases of NF attributed to C neoformans may instead have been caused by C gattii. Misidentification has been compounded by the fact that the tests required for accurate diagnosis of C gattii infection may not be readily available in many clinical microbiology laboratories. Cryptococcus can be identified with various methods, including direct microscopy, culturing of tissue or fluid samples, and measurement of cryptococcal serum antigen. However, tests such as specific culture media, mass spectrometry, and molecular typing studies are required to determine cryptococcal species. L-canavanine-glycine-bromothymol blue (CGB) agar is a medium that is often used to differentiate C gattii from C neoformans because of the ability of C gattii to produce a blue appearance.⁶ Modern techniques, such as MALDI-TOF MS, have also been used to successfully distinguish between C gattii and C neoformans.⁹ MALDI-TOF MS identifies species on the basis of characteristic protein spectra extracted from whole cells. Using commercial and supplemental reference libraries, the system compares signal matches in the reference spectrum with Cryptococcus entries in the library—allowing rapid and accurate identification of cryptococcal species. However, this diagnostic method is limited by availability of adequate Cryptococcus entries in the reference library and by the high cost of acquiring the machine.

Serotyping is based on the antigenic property of the capsule and was once used to differentiate C neoformans into its 3 main varieties: var. neoformans, var. grubii, var. gattii. However, when it was realized that the antigenic property of the strain can be unstable and that there are hybrids containing more than 1 serotype, serotyping was abandoned as a species-differentiation test.⁶ The current gold standard for species differentiation is molecular genotyping. Molecular genotyping studies can confirm the diagnosis of C gattii infection and allow differentiation of C gattii into its 4 main molecular types: VGI, VGII, VGIII, VGIV. Using methods such as polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis, molecular typing allows for specific epidemiology charting of C gattii genotypes.⁷

Although the transmission route for cryptococcal infection is mainly respiratory, direct inoculation has been reported as well.¹⁹ Cutaneous lesions, which occur in 5% to 20% of cryptococcal infections, often present in the head and neck.^2,20,21 Primary cutaneous infections from cryptococcosis are rare, and cutaneous manifestations are often a sign of disseminated disease. Disseminated disease is defined as the involvement of 2 or more noncontiguous sites or evidence of high fungal burden based on cryptococcal antigen titer of more than 1:512.¹² It is important to exclude disseminated disease in all cases of cryptococcosis, as it may be fatal.²⁰ The neural and pulmonary systems should be screened.²² Cellulitis from cryptococcosis is almost always limited to immunocompromised patients, though there are reports of crytococcal cutaneous disease in immunocompetent patients.^3,15 Interestingly, though C neoformans often affects immunocompromised patients, the emerging pathogen of C gattii affects immunocompetent patients.^7,17,23 Our patient’s undiagnosed diabetes may have been a risk factor for cryptococcal infection. His cryptococcal antigen titer was 1:256, with no evidence of other sites of involvement. We therefore believe this to be a rare case of direct inoculation secondary to an insect bite.

The literature includes 12 reported cases of NF secondary to Cryptococcus (Table 2), all C neoformans. Of these cases, 9 involved immunosuppression, and most of these patients were on long-term steroid treatment after organ transplantation. The most common infection site was the lower extremity. These cases of cryptococcal NF show that immunosuppression, and long-term steroid use in particular, is an important risk factor. The mortality rate for these reviewed cases was 41.6% (5/12). According to the literature, the mortality rates for patients with cryptococcal soft-tissue infections²⁴ and posttransplant patients with cryptococcal NF²¹ were 37.5% and 60%, respectively. We believe the mortality rate in our reviewed cases likely was confounded by the fact that most of the patients were posttransplant patients on long-term immunosuppression.

Of the 12 patients, 5 had primary cutaneous disease. There seems to be no relationship between outcome and dissemination of disease. In addition, there is a paucity of literature on the effect of disseminated disease and cryptococcal soft-tissue infections. Therefore, no firm conclusions can be drawn regarding the effects of disseminated disease on severity of cryptococcal soft-tissue infection.

Treatment of cryptococcal NF involves a combination of surgical débridement and long-term antifungal therapy. Surgical débridement of NF includes delineating the extent of infection with complete surgical excision of the affected tissue.²⁵ The aims of surgery should be to remove all unhealthy tissue, identify the offending organism, and plan for resurfacing or reconstruction of the afflicted extremity. Intraoperative-tissue histology should be performed to confirm the diagnosis of NF. Histology can be used to demonstrate cryptococcal infection. The diagnosis of cryptococcal infection can be aided with fungal cultures, and therefore we recommend that tissue cultures be sent not only for routine aerobic/anaerobic bacteria but also for mycobacteria and fungal organisms. Laboratory tests that aid in diagnosis include serum cryptococcal antigen titer.

The current treatment recommendation for cryptococcal disease in patients who are not HIV-positive or transplant hosts is amphotericin B deoxycholate 0.7 to 1.0 mg/kg/d plus flucytosine 100 mg/kg/d for at least 4 weeks.²² The regimen period may be shortened to 14 days for patients at low risk of treatment failure. Fluconazole should be given as maintenance therapy (200 mg/d) for 6 to 12 months. There is no compelling evidence for immunoglobulin therapy for cryptococcal disease.²²

Conclusion

NF caused by Cryptococcus is rare. A high level of suspicion, and intraoperative specimens for histology and fungal microscopy and culture, can help in establishing the diagnosis. Molecular genotyping remains the diagnostic method of choice for NF secondary to Cryptococcus. Effective treatment consists of aggressive surgical débridement and antifungal therapy.

With an incidence of 75,000 per year in the United States alone, fractures of the tibial shaft are among the most common long-bone fractures.¹ Diaphyseal tibial fractures present a unique treatment challenge because of complications, including nonunion, malunion, and the potential for an open injury. Intramedullary fixation of these fractures has long been the standard of care, allowing for early mobilization, shorter time to weight-bearing, and high union rates.^2-4

The classic infrapatellar approach to intramedullary nailing involves placing the knee in hyperflexion over a bump or radiolucent triangle and inserting the nail through a longitudinal incision in line with the fibers of the patellar tendon. Deforming muscle forces often cause proximal-third tibial fractures and segmental fractures to fall into valgus and procurvatum. To counter these deforming forces, orthopedic surgeons have used some novel surgical approaches, including use of blocking screws⁵ and a parapatellar approach that could be used with the knee in semi-extended position.⁶ Anterior knee pain has been reported as a common complication of tibial nailing (reported incidence, 56%).⁷ In a prospective randomized controlled study, Toivanen and colleagues⁸ found no difference in incidence of knee pain between patellar tendon splitting and parapatellar approaches.

Techniques have been developed to insert the nail through a semi-extended suprapatellar approach to facilitate intraoperative imaging, allow easier access to starting-site position, and counter deforming forces. Although outcomes of traditional infrapatellar nailing have been well documented, there is a paucity of literature on outcomes of using a suprapatellar approach. Splitting the quadriceps tendon causes scar tissue to form superior to the patella versus the anterior knee, which may reduce flexion-related pain or kneeling pain.⁹ The infrapatellar nerve is also well protected with this approach.

We conducted a study to determine differences in functional knee pain in patients who underwent either traditional infrapatellar nailing or suprapatellar nailing. We hypothesized that there would be no difference in functional knee scores between these approaches and that, when compared with the infrapatellar approach, the suprapatellar approach would result in improved postoperative reduction and reduced intraoperative fluoroscopy time.

Materials and Methods

This study was approved by our institutional review board. We searched our level I trauma center’s database for Current Procedural Terminology (CPT) code 27759 to identify all patients who had a tibial shaft fracture fixed with an intramedullary implant between January 2009 and February 2013. Radiographs, operative reports, and inpatient records were reviewed. Patients older than 18 years at time of injury and patients with an isolated tibial shaft fracture (Orthopaedic Trauma Association type 42 A-C) surgically fixed with an intramedullary nail through either a traditional infrapatellar approach or a suprapatellar approach were included in the study. Exclusion criteria were required fasciotomy, Gustilo type 3B or 3C open fracture, prior knee surgery, additional orthopedic injury, and preexisting radiographic evidence of degenerative joint disease.

In addition to surgical approach, demographic data, including body mass index (BMI), age, sex, and mechanism of injury, were documented from the medical record. Each patient was contacted by telephone by an investigator blinded to surgical exposure, and the 12-item Oxford Knee Score (OKS) questionnaire was administered (Figure). Operative time, quality of reduction on postoperative radiographs, and intraoperative fluoroscopy time were compared between the 2 approaches. We determined quality of reduction by measuring the angle between the line perpendicular to the tibial plateau and plafond on both the anteroposterior and lateral postoperative radiographs. Rotation was determined by measuring displacement of the fracture by cortical widths. The infrapatellar and suprapatellar groups were statistically analyzed with an unpaired, 2-tailed Student t test. Categorical variables between groups were analyzed with the χ² test or, when expected values in a cell were less than 5, the Fisher exact test.

We then conducted an a priori power analysis to determine the appropriate sample size. To detect the reported minimally clinically important difference in the OKS of 5.2,¹⁰ estimating an approximate 20% larger patient population in the infrapatellar group, we would need to enroll 24 infrapatellar patients and 20 suprapatellar patients to achieve a power of 0.80 with a type I error rate of 0.05.¹¹ This analysis is also based on an estimated OKS standard deviation of 6, which has been reported in several studies.^12,13

Results

We identified 176 patients who had the CPT code for intramedullary fixation of a tibial shaft fracture between January 2009 and February 2013. After analysis of radiographs and medical records, 82 patients met the inclusion criteria. Thirty-six (45%) of the original 82 patients were lost to follow-up after attempts to contact them by telephone. One patient refused to participate in the study. Twenty-four patients underwent traditional infrapatellar nailing, and 21 patients had a suprapatellar nail placed with approach-specific instrumentation. Nine patients had an open fracture. There was no significant difference between the groups in terms of sex, age, BMI, mechanism of injury, or operative time (Table 1). There was also no difference (P = .210) in fracture location between groups (0 proximal-third, 14 midshaft, 10 distal-third vs 3 proximal-third, 10 midshaft, 8 distal-third). Mean age was 37.6 years (range, 20-65 years) for the infrapatellar group and 38.5 years (range, 18-68 years) for the suprapatellar group (P = .839). Mean follow-up was significantly (P < .001) shorter for the suprapatellar group (12 mo; range, 3-33 mo) than for the infrapatellar group (25 mo; range, 4-43 mo).

Mean OKS (maximum, 48 points) was 40.1 (range, 11-48) for the infrapatellar group and 36.7 (range, 2-48) for the suprapatellar group (P = .293). Table 2 summarizes the data. Radiographic reduction in the sagittal plane was improved (P = .044) in the suprapatellar group (2.90°) compared with the infrapatellar group (4.58°). There was no difference in rotational malreduction (0.31 vs 0.25 cortical width; P = .599) or in reduction in the coronal plane (2.52° vs 3.17°; P = .280). All patients in both groups maintained radiographic reduction within 5° in any plane throughout follow-up. There was no difference (P = .654) in radiographic follow-up between the infrapatellar group (11 mo) and the suprapatellar group (12 mo). The 1 nonunion in the suprapatellar group required return to the operating room for exchange intramedullary nailing. The suprapatellar approach required less (P = .003) operative fluoroscopy time (80.8 s; range, 46-180 s) than the standard infrapatellar approach (122.1 s; range, 71-240 s). Two patients in the suprapatellar group and 8 in the infrapatellar group did not have their fluoroscopy time recorded in the operative report.

Discussion

We have described the first retrospective cohort-comparison study of functional knee scores associated with traditional infrapatellar nailing and suprapatellar nailing. Although much has been written about the incidence of anterior knee pain with use of a patellar splitting or parapatellar approach, the clinical effects of knee pain after use of suprapatellar nails are yet to be addressed. In a cadaveric study, Gelbke and colleagues¹⁴ found higher mean patellofemoral pressures and higher peak contact pressures with a suprapatellar approach. These numbers, however, were still far below the threshold for chondrocyte damage, and that study is yet to be clinically validated. Our data showed no difference in OKS between the 2 groups. Despite being intra-articular, approach-specific instrumentation may protect the trochlea and patellar cartilage.

Although the OKS questionnaire was originally developed and widely validated to describe clinical outcomes of total knee arthroplasty,^15,16 it has also been evaluated for other interventions, including viscosupplementation injections¹⁷ and high tibial osteotomy.¹⁸ We used the OKS questionnaire in our study because it is simple to administer by telephone and is not as cumbersome as the Knee Society Score or the Western Ontario and McMaster Universities Osteoarthritis Index. It is also more specific to the knee than generalized outcome measures used in trauma, such as the Short Form 36 (SF-36). Sanders and colleagues¹⁹ reported excellent tibial alignment, radiographic union, and knee range of motion using semi-extended tibial nailing with a suprapatellar approach. For outcome measures, they used the Lysholm Knee Score and the SF-36. Our clinical and radiographic results confirmed their finding—that the semi-extended suprapatellar approach is an option for tibial nailing.

OKS results by question (Table 3) showed that the infrapatellar group had less pain walking down stairs. This result approached statistical significance (P = .063). As surgeons at our institution began using the suprapatellar approach only during the final 2 years of the study period, mean follow-up was significantly (P < .001) less than for the infrapatellar group (12 vs 25 mo). Although there was no statistically significant difference in reduction quality on anteroposterior radiographs, the suprapatellar approach had improved (P = .044) reduction on lateral radiographs (2.90° vs 4.58°).

Although operative time did not differ between our 2 groups, significantly (P = .003) less fluoroscopy time was required for suprapatellar nails (80.8 s) than for infrapatellar nails (122.1 s). Positioning the knee in the semi-extended position offers easier access for fluoroscopy and less radiation exposure for the patient. Placing the nail in extension also helps eliminate the deforming forces that cause malreduction of proximal tibial shaft or segmental fractures. However, our study was limited in that only 2 surgeons at our institution used the suprapatellar approach, and both were fellowship-trained in orthopedic traumatology. This situation could have introduced bias into the interpretation of fluoroscopy data, as these surgeons may have been more comfortable with the procedure and less likely to use fluoroscopy. Both surgeons also performed infrapatellar nailing during the study period, and there was no statistical difference in fracture patterns between the groups, thus minimizing bias.

This study was retrospective but had several strengths. Sample size met the prestudy power analysis to determine a minimally clinically important difference in OKS results. The investigator who administered the telephone survey was blinded to surgical approach. This study was also the first clinical study to compare outcomes of infrapatellar and suprapatellar nailing. However, the study’s follow-up rate was a weakness. The patient population at our academic, urban, level I trauma center is transient. We lost 36 patients (45%) to follow-up; their telephone numbers in the hospital records likely changed since surgery, and we could not contact these patients.

Conclusion

Our retrospective cohort study found no difference in OKS between traditional infrapatellar nailing and suprapatellar nailing for diaphyseal tibia fractures. Suprapatellar nails require less fluoroscopy time and may show improved radiographic reduction in the sagittal plane. Although further study is needed, the suprapatellar entry portal appears to be a safe alternative for tibial nailing with use of appropriate instrumentation.

With an incidence of 75,000 per year in the United States alone, fractures of the tibial shaft are among the most common long-bone fractures.¹ Diaphyseal tibial fractures present a unique treatment challenge because of complications, including nonunion, malunion, and the potential for an open injury. Intramedullary fixation of these fractures has long been the standard of care, allowing for early mobilization, shorter time to weight-bearing, and high union rates.^2-4

The classic infrapatellar approach to intramedullary nailing involves placing the knee in hyperflexion over a bump or radiolucent triangle and inserting the nail through a longitudinal incision in line with the fibers of the patellar tendon. Deforming muscle forces often cause proximal-third tibial fractures and segmental fractures to fall into valgus and procurvatum. To counter these deforming forces, orthopedic surgeons have used some novel surgical approaches, including use of blocking screws⁵ and a parapatellar approach that could be used with the knee in semi-extended position.⁶ Anterior knee pain has been reported as a common complication of tibial nailing (reported incidence, 56%).⁷ In a prospective randomized controlled study, Toivanen and colleagues⁸ found no difference in incidence of knee pain between patellar tendon splitting and parapatellar approaches.

Techniques have been developed to insert the nail through a semi-extended suprapatellar approach to facilitate intraoperative imaging, allow easier access to starting-site position, and counter deforming forces. Although outcomes of traditional infrapatellar nailing have been well documented, there is a paucity of literature on outcomes of using a suprapatellar approach. Splitting the quadriceps tendon causes scar tissue to form superior to the patella versus the anterior knee, which may reduce flexion-related pain or kneeling pain.⁹ The infrapatellar nerve is also well protected with this approach.

We conducted a study to determine differences in functional knee pain in patients who underwent either traditional infrapatellar nailing or suprapatellar nailing. We hypothesized that there would be no difference in functional knee scores between these approaches and that, when compared with the infrapatellar approach, the suprapatellar approach would result in improved postoperative reduction and reduced intraoperative fluoroscopy time.

Materials and Methods

This study was approved by our institutional review board. We searched our level I trauma center’s database for Current Procedural Terminology (CPT) code 27759 to identify all patients who had a tibial shaft fracture fixed with an intramedullary implant between January 2009 and February 2013. Radiographs, operative reports, and inpatient records were reviewed. Patients older than 18 years at time of injury and patients with an isolated tibial shaft fracture (Orthopaedic Trauma Association type 42 A-C) surgically fixed with an intramedullary nail through either a traditional infrapatellar approach or a suprapatellar approach were included in the study. Exclusion criteria were required fasciotomy, Gustilo type 3B or 3C open fracture, prior knee surgery, additional orthopedic injury, and preexisting radiographic evidence of degenerative joint disease.

In addition to surgical approach, demographic data, including body mass index (BMI), age, sex, and mechanism of injury, were documented from the medical record. Each patient was contacted by telephone by an investigator blinded to surgical exposure, and the 12-item Oxford Knee Score (OKS) questionnaire was administered (Figure). Operative time, quality of reduction on postoperative radiographs, and intraoperative fluoroscopy time were compared between the 2 approaches. We determined quality of reduction by measuring the angle between the line perpendicular to the tibial plateau and plafond on both the anteroposterior and lateral postoperative radiographs. Rotation was determined by measuring displacement of the fracture by cortical widths. The infrapatellar and suprapatellar groups were statistically analyzed with an unpaired, 2-tailed Student t test. Categorical variables between groups were analyzed with the χ² test or, when expected values in a cell were less than 5, the Fisher exact test.

We then conducted an a priori power analysis to determine the appropriate sample size. To detect the reported minimally clinically important difference in the OKS of 5.2,¹⁰ estimating an approximate 20% larger patient population in the infrapatellar group, we would need to enroll 24 infrapatellar patients and 20 suprapatellar patients to achieve a power of 0.80 with a type I error rate of 0.05.¹¹ This analysis is also based on an estimated OKS standard deviation of 6, which has been reported in several studies.^12,13

Results

We identified 176 patients who had the CPT code for intramedullary fixation of a tibial shaft fracture between January 2009 and February 2013. After analysis of radiographs and medical records, 82 patients met the inclusion criteria. Thirty-six (45%) of the original 82 patients were lost to follow-up after attempts to contact them by telephone. One patient refused to participate in the study. Twenty-four patients underwent traditional infrapatellar nailing, and 21 patients had a suprapatellar nail placed with approach-specific instrumentation. Nine patients had an open fracture. There was no significant difference between the groups in terms of sex, age, BMI, mechanism of injury, or operative time (Table 1). There was also no difference (P = .210) in fracture location between groups (0 proximal-third, 14 midshaft, 10 distal-third vs 3 proximal-third, 10 midshaft, 8 distal-third). Mean age was 37.6 years (range, 20-65 years) for the infrapatellar group and 38.5 years (range, 18-68 years) for the suprapatellar group (P = .839). Mean follow-up was significantly (P < .001) shorter for the suprapatellar group (12 mo; range, 3-33 mo) than for the infrapatellar group (25 mo; range, 4-43 mo).

Mean OKS (maximum, 48 points) was 40.1 (range, 11-48) for the infrapatellar group and 36.7 (range, 2-48) for the suprapatellar group (P = .293). Table 2 summarizes the data. Radiographic reduction in the sagittal plane was improved (P = .044) in the suprapatellar group (2.90°) compared with the infrapatellar group (4.58°). There was no difference in rotational malreduction (0.31 vs 0.25 cortical width; P = .599) or in reduction in the coronal plane (2.52° vs 3.17°; P = .280). All patients in both groups maintained radiographic reduction within 5° in any plane throughout follow-up. There was no difference (P = .654) in radiographic follow-up between the infrapatellar group (11 mo) and the suprapatellar group (12 mo). The 1 nonunion in the suprapatellar group required return to the operating room for exchange intramedullary nailing. The suprapatellar approach required less (P = .003) operative fluoroscopy time (80.8 s; range, 46-180 s) than the standard infrapatellar approach (122.1 s; range, 71-240 s). Two patients in the suprapatellar group and 8 in the infrapatellar group did not have their fluoroscopy time recorded in the operative report.

Discussion

We have described the first retrospective cohort-comparison study of functional knee scores associated with traditional infrapatellar nailing and suprapatellar nailing. Although much has been written about the incidence of anterior knee pain with use of a patellar splitting or parapatellar approach, the clinical effects of knee pain after use of suprapatellar nails are yet to be addressed. In a cadaveric study, Gelbke and colleagues¹⁴ found higher mean patellofemoral pressures and higher peak contact pressures with a suprapatellar approach. These numbers, however, were still far below the threshold for chondrocyte damage, and that study is yet to be clinically validated. Our data showed no difference in OKS between the 2 groups. Despite being intra-articular, approach-specific instrumentation may protect the trochlea and patellar cartilage.

Although the OKS questionnaire was originally developed and widely validated to describe clinical outcomes of total knee arthroplasty,^15,16 it has also been evaluated for other interventions, including viscosupplementation injections¹⁷ and high tibial osteotomy.¹⁸ We used the OKS questionnaire in our study because it is simple to administer by telephone and is not as cumbersome as the Knee Society Score or the Western Ontario and McMaster Universities Osteoarthritis Index. It is also more specific to the knee than generalized outcome measures used in trauma, such as the Short Form 36 (SF-36). Sanders and colleagues¹⁹ reported excellent tibial alignment, radiographic union, and knee range of motion using semi-extended tibial nailing with a suprapatellar approach. For outcome measures, they used the Lysholm Knee Score and the SF-36. Our clinical and radiographic results confirmed their finding—that the semi-extended suprapatellar approach is an option for tibial nailing.

OKS results by question (Table 3) showed that the infrapatellar group had less pain walking down stairs. This result approached statistical significance (P = .063). As surgeons at our institution began using the suprapatellar approach only during the final 2 years of the study period, mean follow-up was significantly (P < .001) less than for the infrapatellar group (12 vs 25 mo). Although there was no statistically significant difference in reduction quality on anteroposterior radiographs, the suprapatellar approach had improved (P = .044) reduction on lateral radiographs (2.90° vs 4.58°).

Although operative time did not differ between our 2 groups, significantly (P = .003) less fluoroscopy time was required for suprapatellar nails (80.8 s) than for infrapatellar nails (122.1 s). Positioning the knee in the semi-extended position offers easier access for fluoroscopy and less radiation exposure for the patient. Placing the nail in extension also helps eliminate the deforming forces that cause malreduction of proximal tibial shaft or segmental fractures. However, our study was limited in that only 2 surgeons at our institution used the suprapatellar approach, and both were fellowship-trained in orthopedic traumatology. This situation could have introduced bias into the interpretation of fluoroscopy data, as these surgeons may have been more comfortable with the procedure and less likely to use fluoroscopy. Both surgeons also performed infrapatellar nailing during the study period, and there was no statistical difference in fracture patterns between the groups, thus minimizing bias.

This study was retrospective but had several strengths. Sample size met the prestudy power analysis to determine a minimally clinically important difference in OKS results. The investigator who administered the telephone survey was blinded to surgical approach. This study was also the first clinical study to compare outcomes of infrapatellar and suprapatellar nailing. However, the study’s follow-up rate was a weakness. The patient population at our academic, urban, level I trauma center is transient. We lost 36 patients (45%) to follow-up; their telephone numbers in the hospital records likely changed since surgery, and we could not contact these patients.

Conclusion

Our retrospective cohort study found no difference in OKS between traditional infrapatellar nailing and suprapatellar nailing for diaphyseal tibia fractures. Suprapatellar nails require less fluoroscopy time and may show improved radiographic reduction in the sagittal plane. Although further study is needed, the suprapatellar entry portal appears to be a safe alternative for tibial nailing with use of appropriate instrumentation.

With an incidence of 75,000 per year in the United States alone, fractures of the tibial shaft are among the most common long-bone fractures.¹ Diaphyseal tibial fractures present a unique treatment challenge because of complications, including nonunion, malunion, and the potential for an open injury. Intramedullary fixation of these fractures has long been the standard of care, allowing for early mobilization, shorter time to weight-bearing, and high union rates.^2-4

The classic infrapatellar approach to intramedullary nailing involves placing the knee in hyperflexion over a bump or radiolucent triangle and inserting the nail through a longitudinal incision in line with the fibers of the patellar tendon. Deforming muscle forces often cause proximal-third tibial fractures and segmental fractures to fall into valgus and procurvatum. To counter these deforming forces, orthopedic surgeons have used some novel surgical approaches, including use of blocking screws⁵ and a parapatellar approach that could be used with the knee in semi-extended position.⁶ Anterior knee pain has been reported as a common complication of tibial nailing (reported incidence, 56%).⁷ In a prospective randomized controlled study, Toivanen and colleagues⁸ found no difference in incidence of knee pain between patellar tendon splitting and parapatellar approaches.

Techniques have been developed to insert the nail through a semi-extended suprapatellar approach to facilitate intraoperative imaging, allow easier access to starting-site position, and counter deforming forces. Although outcomes of traditional infrapatellar nailing have been well documented, there is a paucity of literature on outcomes of using a suprapatellar approach. Splitting the quadriceps tendon causes scar tissue to form superior to the patella versus the anterior knee, which may reduce flexion-related pain or kneeling pain.⁹ The infrapatellar nerve is also well protected with this approach.

We conducted a study to determine differences in functional knee pain in patients who underwent either traditional infrapatellar nailing or suprapatellar nailing. We hypothesized that there would be no difference in functional knee scores between these approaches and that, when compared with the infrapatellar approach, the suprapatellar approach would result in improved postoperative reduction and reduced intraoperative fluoroscopy time.

Materials and Methods

This study was approved by our institutional review board. We searched our level I trauma center’s database for Current Procedural Terminology (CPT) code 27759 to identify all patients who had a tibial shaft fracture fixed with an intramedullary implant between January 2009 and February 2013. Radiographs, operative reports, and inpatient records were reviewed. Patients older than 18 years at time of injury and patients with an isolated tibial shaft fracture (Orthopaedic Trauma Association type 42 A-C) surgically fixed with an intramedullary nail through either a traditional infrapatellar approach or a suprapatellar approach were included in the study. Exclusion criteria were required fasciotomy, Gustilo type 3B or 3C open fracture, prior knee surgery, additional orthopedic injury, and preexisting radiographic evidence of degenerative joint disease.

In addition to surgical approach, demographic data, including body mass index (BMI), age, sex, and mechanism of injury, were documented from the medical record. Each patient was contacted by telephone by an investigator blinded to surgical exposure, and the 12-item Oxford Knee Score (OKS) questionnaire was administered (Figure). Operative time, quality of reduction on postoperative radiographs, and intraoperative fluoroscopy time were compared between the 2 approaches. We determined quality of reduction by measuring the angle between the line perpendicular to the tibial plateau and plafond on both the anteroposterior and lateral postoperative radiographs. Rotation was determined by measuring displacement of the fracture by cortical widths. The infrapatellar and suprapatellar groups were statistically analyzed with an unpaired, 2-tailed Student t test. Categorical variables between groups were analyzed with the χ² test or, when expected values in a cell were less than 5, the Fisher exact test.

We then conducted an a priori power analysis to determine the appropriate sample size. To detect the reported minimally clinically important difference in the OKS of 5.2,¹⁰ estimating an approximate 20% larger patient population in the infrapatellar group, we would need to enroll 24 infrapatellar patients and 20 suprapatellar patients to achieve a power of 0.80 with a type I error rate of 0.05.¹¹ This analysis is also based on an estimated OKS standard deviation of 6, which has been reported in several studies.^12,13

Results

We identified 176 patients who had the CPT code for intramedullary fixation of a tibial shaft fracture between January 2009 and February 2013. After analysis of radiographs and medical records, 82 patients met the inclusion criteria. Thirty-six (45%) of the original 82 patients were lost to follow-up after attempts to contact them by telephone. One patient refused to participate in the study. Twenty-four patients underwent traditional infrapatellar nailing, and 21 patients had a suprapatellar nail placed with approach-specific instrumentation. Nine patients had an open fracture. There was no significant difference between the groups in terms of sex, age, BMI, mechanism of injury, or operative time (Table 1). There was also no difference (P = .210) in fracture location between groups (0 proximal-third, 14 midshaft, 10 distal-third vs 3 proximal-third, 10 midshaft, 8 distal-third). Mean age was 37.6 years (range, 20-65 years) for the infrapatellar group and 38.5 years (range, 18-68 years) for the suprapatellar group (P = .839). Mean follow-up was significantly (P < .001) shorter for the suprapatellar group (12 mo; range, 3-33 mo) than for the infrapatellar group (25 mo; range, 4-43 mo).

Mean OKS (maximum, 48 points) was 40.1 (range, 11-48) for the infrapatellar group and 36.7 (range, 2-48) for the suprapatellar group (P = .293). Table 2 summarizes the data. Radiographic reduction in the sagittal plane was improved (P = .044) in the suprapatellar group (2.90°) compared with the infrapatellar group (4.58°). There was no difference in rotational malreduction (0.31 vs 0.25 cortical width; P = .599) or in reduction in the coronal plane (2.52° vs 3.17°; P = .280). All patients in both groups maintained radiographic reduction within 5° in any plane throughout follow-up. There was no difference (P = .654) in radiographic follow-up between the infrapatellar group (11 mo) and the suprapatellar group (12 mo). The 1 nonunion in the suprapatellar group required return to the operating room for exchange intramedullary nailing. The suprapatellar approach required less (P = .003) operative fluoroscopy time (80.8 s; range, 46-180 s) than the standard infrapatellar approach (122.1 s; range, 71-240 s). Two patients in the suprapatellar group and 8 in the infrapatellar group did not have their fluoroscopy time recorded in the operative report.

Discussion

We have described the first retrospective cohort-comparison study of functional knee scores associated with traditional infrapatellar nailing and suprapatellar nailing. Although much has been written about the incidence of anterior knee pain with use of a patellar splitting or parapatellar approach, the clinical effects of knee pain after use of suprapatellar nails are yet to be addressed. In a cadaveric study, Gelbke and colleagues¹⁴ found higher mean patellofemoral pressures and higher peak contact pressures with a suprapatellar approach. These numbers, however, were still far below the threshold for chondrocyte damage, and that study is yet to be clinically validated. Our data showed no difference in OKS between the 2 groups. Despite being intra-articular, approach-specific instrumentation may protect the trochlea and patellar cartilage.

Although the OKS questionnaire was originally developed and widely validated to describe clinical outcomes of total knee arthroplasty,^15,16 it has also been evaluated for other interventions, including viscosupplementation injections¹⁷ and high tibial osteotomy.¹⁸ We used the OKS questionnaire in our study because it is simple to administer by telephone and is not as cumbersome as the Knee Society Score or the Western Ontario and McMaster Universities Osteoarthritis Index. It is also more specific to the knee than generalized outcome measures used in trauma, such as the Short Form 36 (SF-36). Sanders and colleagues¹⁹ reported excellent tibial alignment, radiographic union, and knee range of motion using semi-extended tibial nailing with a suprapatellar approach. For outcome measures, they used the Lysholm Knee Score and the SF-36. Our clinical and radiographic results confirmed their finding—that the semi-extended suprapatellar approach is an option for tibial nailing.

OKS results by question (Table 3) showed that the infrapatellar group had less pain walking down stairs. This result approached statistical significance (P = .063). As surgeons at our institution began using the suprapatellar approach only during the final 2 years of the study period, mean follow-up was significantly (P < .001) less than for the infrapatellar group (12 vs 25 mo). Although there was no statistically significant difference in reduction quality on anteroposterior radiographs, the suprapatellar approach had improved (P = .044) reduction on lateral radiographs (2.90° vs 4.58°).

Although operative time did not differ between our 2 groups, significantly (P = .003) less fluoroscopy time was required for suprapatellar nails (80.8 s) than for infrapatellar nails (122.1 s). Positioning the knee in the semi-extended position offers easier access for fluoroscopy and less radiation exposure for the patient. Placing the nail in extension also helps eliminate the deforming forces that cause malreduction of proximal tibial shaft or segmental fractures. However, our study was limited in that only 2 surgeons at our institution used the suprapatellar approach, and both were fellowship-trained in orthopedic traumatology. This situation could have introduced bias into the interpretation of fluoroscopy data, as these surgeons may have been more comfortable with the procedure and less likely to use fluoroscopy. Both surgeons also performed infrapatellar nailing during the study period, and there was no statistical difference in fracture patterns between the groups, thus minimizing bias.

This study was retrospective but had several strengths. Sample size met the prestudy power analysis to determine a minimally clinically important difference in OKS results. The investigator who administered the telephone survey was blinded to surgical approach. This study was also the first clinical study to compare outcomes of infrapatellar and suprapatellar nailing. However, the study’s follow-up rate was a weakness. The patient population at our academic, urban, level I trauma center is transient. We lost 36 patients (45%) to follow-up; their telephone numbers in the hospital records likely changed since surgery, and we could not contact these patients.

Conclusion

Our retrospective cohort study found no difference in OKS between traditional infrapatellar nailing and suprapatellar nailing for diaphyseal tibia fractures. Suprapatellar nails require less fluoroscopy time and may show improved radiographic reduction in the sagittal plane. Although further study is needed, the suprapatellar entry portal appears to be a safe alternative for tibial nailing with use of appropriate instrumentation.

First described by Runge¹ in 1873 and later termed lawn-tennis arm by Major² in 1883, lateral epicondylitis is a common cause of elbow pain, affecting 1% to 3% of the general population each year.^3,4 Given that prevalence estimates are up to 15% among workers in repetitive hand task industries,^5-7 symptoms of lateral epicondylitis are thought to be related to recurring wrist extension and alternating forearm pronation and supination.⁸ Between 80% and 90% of patients with lateral epicondylitis experience symptomatic improvement with conservative therapy,^9-11 including rest and use of nonsteroidal anti-inflammatory medications,¹² physical therapy,^13,14 corticosteroid injections,^10,15,16 orthoses,^17,18 and shock wave therapy.¹⁹ However, between 4% and 11% of patients with newly diagnosed lateral epicondylitis do not respond to prolonged (6- to 12-month) conservative treatment and then require operative intervention,^11,20,21 with some referral practices reporting rates as high as 25%.²²

Traditionally, operative management of lateral epicondylitis involved open débridement of the extensor carpi radialis brevis (ECRB).^11,20 More recently, the spectrum of operations for lateral epicondylitis has expanded to include procedures that repair the extensor origin after débridement of the torn tendon and angiofibroblastic dysplasia; procedures that use fasciotomy or direct release of the extensor origin from the epicondyle to relieve tension on the common extensor; procedures directed at the radial or posterior interosseous nerve; and procedures that use arthroscopic techniques to divide the orbicular ligament, reshape the radial head, or release the extensor origin.²³ There has been debate about the value of repairing the ECRB, lengthening the ECRB, simultaneously decompressing the radial nerve or resecting epicondylar bone, and performing the procedures percutaneously, endoscopically, or arthroscopically.^24-28 Despite multiple studies of the outcomes of these procedures,^11,29-31 little is known regarding US national trends for operative treatment of lateral epicondylitis. Understanding national practice patterns and disease burden is essential to allocation of limited health care resources.

We conducted a study to determine US national trends in use of ambulatory surgery for lateral epicondylitis. We focused on age, sex, surgical setting, anesthetic type, and payment method.

Methods

As the National Survey of Ambulatory Surgery³² (NSAS) is an administrative dataset in which all data are deidentified and available for public use, this study was exempt from requiring institutional review board approval.

NSAS data were used to analyze trends in treatment of lateral epicondylitis between 1994 and 2006. NSAS was undertaken by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC) to obtain information about the use of ambulatory surgery in the United States. Since the early 1980s, ambulatory surgery has increased in the United States because of advances in medical technology and cost-containment initiatives.³³ The number of procedures being performed in ambulatory surgery centers increased from 31.5 million in 1996 to 53.3 million in 2006.³⁴ Funded by the CDC, NSAS is a national study that involves both hospital-based and freestanding ambulatory surgery centers and provides the most recent and comprehensive overview of ambulatory surgery in the United States.³⁵ Because of budgetary limitations, 2006 was the last year in which data for NSAS were collected. Data for NSAS come from Medicare-participating, noninstitutional hospitals (excluding military hospitals, federal facilities, and Veteran Affairs hospitals) in all 50 states and the District of Columbia with a minimum of 6 beds staffed for patient use. NSAS used only short-stay hospitals (hospitals with an average length of stay for all patients of less than 30 days) or hospitals that had a specialty of general (medical or surgical) or children’s general. NSAS was conducted in 1994, 1996, and 2006 with medical information recorded on patient abstracts coded by contract staff. NSAS selected a sample of ambulatory surgery visits using a systematic random sampling procedure, and selection of visits within each facility was done separately for each location where ambulatory surgery was performed. In 1994, 751 facilities were sampled, and 88% of hospitals responded. In 1996, 750 facilities were sampled, and 91% of hospitals responded. In 2006, 696 facilities were sampled, and 75% responded. The surveys used International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes³⁶ to classify medical diagnoses and procedures. To produce an unbiased national estimate, NCHS used multistage estimate procedures, including inflation by reciprocals of the probabilities of sample selection, population-weighting ratio adjustments, and adjustment for no response.³⁷

Demographic and medical information was obtained for people with an ICD-9-CM diagnosis code of lateral epicondylitis (726.32), using previously described techniques.³⁸ Data were then recorded for age, sex, facility type, insurance type, anesthesia type, diagnoses, and procedures.

Descriptive statistics consisted of means and standard deviations for continuous variables and frequency and percentages for discrete variables. Because NSAS data were collected on the basis of a probabilistic sample scheme, they were analyzed using a sampling weighting method. Sampling weights (inverse of selection probability) provided by the CDC were used to account for unequal sampling probabilities and to produce estimates for all visits in the United States. A Taylor linearization model provided by the CDC estimates was used to calculate standard error and confidence intervals (CIs) of the data. Standard error is a measure of sampling variability that occurs by chance because only a sample rather than the entire universe is surveyed. To define population parameters, NCHS chose 95% CIs along with a point estimate. Direct statistical comparison between years cannot be performed because of sampling differences in the database compared between years. The CIs, however, can suggest statistical differences if the data are nonoverlapping. US census data were used to obtain national population estimates for each year of the study (1994, 1996, 2006).³⁹ Rates were presented as number of procedures per 100,000 standard population. For age, a direct adjustment procedure was used, and the US population in 2000 was selected as the standard population. Applying sex-specific rates to the standard population and dividing by the total in the standard population, we calculated sex-adjusted rates for each year. All data were analyzed using SPSS Version 20 software.

Results

A total of 30,311 ambulatory surgical procedures (95% CI, 27,292-33,330) or 10.44 per 100,000 capita were recorded by NSAS for the treatment of lateral epicondylitis in 2006 (Table 1). This represents a large increase in the total number of ambulatory procedures, from 21,852 in 1994 (95% CI, 19,981-23,722; 7.29/100,000) and 20,372 in 1996 (95% CI, 18,660-22,083; 6.73/100,000).

Between 1994 and 2006, the sex-adjusted rate of ambulatory surgery for lateral epicondylitis increased by 85% among females (7.74/100,000 to 14.31/100,000), whereas the rate decreased by 31% among males (8.07/100,000 to 5.59/100,000) (Table 1). The age-adjusted rate of ambulatory surgery for lateral epicondylitis increased among all age groups except the 30–39 years group (Table 2). The largest increase in age-adjusted rates was found for patients older than 50 years (275%) between 1994 and 2006.

During the study period, use of regional anesthesia nearly doubled, from 17% to 30%, whereas use of general anesthesia decreased, from 69% to 57% (Table 3). At all time points, the most common procedure performed for lateral epicondylitis in ambulatory surgery centers was division/release of the joint capsule of the elbow (Table 4). Private insurance remained the most common source of payment for all study years, ranging from 52% to 60% (Table 5). The Figure shows that, between 1994 and 2006, the proportion of surgeries performed in a freestanding ambulatory center increased.

Discussion

In this descriptive epidemiologic study, we used NSAS data to investigate trends in ambulatory surgery for lateral epicondylitis between 1994 and 2006.³² Our results showed that total number of procedures and the population-adjusted rate of procedures for lateral epicondylitis increased during the study period. The largest increase in age-adjusted rates of surgery for lateral epicondylitis was found among patients older than 50 years, whereas the highest age-adjusted rate of ambulatory surgery for lateral epicondylitis was found among patients between ages 40 and 49 years. These findings are similar to those of previous studies, which have shown that most patients with lateral epicondylitis present in the fourth and fifth decades of life.²² Prior reports have suggested that the incidence of lateral epicondylitis in men and women is equal.²² The present study found a change in sex-adjusted rates of ambulatory surgery for lateral epicondylitis between 1994 and 2006. Specifically, in 1994, surgery rates for men and women were similar (8.07/100,000 and 7.74/100,000), but in 2006 the sex-adjusted rate of surgery for lateral epicondylitis was almost 3 times higher for women than for men (14.31/100,000 vs 5.59/100,000).

We also found that the population-adjusted rate of lateral epicondylectomy increased drastically, from 0.4 per 100,000 in 1994 to 3.53 per 100,000 in 2006. Lateral epicondylectomy involves excision of the tip of the lateral epicondyle (typically, 0.5 cm) to produce a cancellous bone surface to which the edges of the débrided extensor tendon can be approximated without tension.²³ It is possible that the increased rate of lateral epicondylectomy reflects evidence-based practice changes during the study period,²⁷ though denervation was found more favorable than epicondylectomy in a recent study by Berry and colleagues.⁴⁰ Future studies should investigate whether rates of epicondylectomy have changed since 2006. In addition, the present study showed a correlation between the introduction of arthroscopic techniques for the treatment of lateral epicondylitis and the period when much research was being conducted on the topic.^24,25,28 As arthroscopic techniques improve, their rates are likely to continue to increase.

Our results also showed an increase in procedures performed in freestanding facilities. The rise in ambulatory surgical volume, speculated to result from more procedures being performed in freestanding facilities,³⁴ has been reported with knee and shoulder arthroscopy.⁴¹ In addition, though general anesthesia remained the most used technique, our results showed a shift toward peripheral nerve blocks. The increase in regional anesthesia, which has also been noted in joint arthroscopy, is thought to stem from the advent of nerve-localizing technology, such as nerve stimulation and ultrasound guidance.⁴¹ Peripheral nerve blocks are favorable on both economic and quality measures, are associated with fewer opioid-related side effects, and overall provide better analgesia in comparison with opioids, highlighting their importance in the ambulatory setting.⁴²

Although large, national databases are well suited to epidemiologic research,⁴³ our study had limitations. As with all databases, NSAS is subject to data entry errors and coding errors.^44,45 However, the database administrators corrected for this by using a multistage estimate procedure with weighting adjustments for no response and population-weighting ratio adjustments.³⁵ Another limitation of this study is its lack of clinical detail, as procedure codes are general and do not allow differentiation between specific patients. Because of the retrospective nature of the analysis and the heterogeneity of the data, assessment of specific surgeries for lateral epicondylitis was limited. Although a strength of using NSAS to perform epidemiologic analyses is its large sample size, this also sacrifices specificity in terms of clinical insight. The results of this study may influence investigations to distinguish differences between procedures used in the treatment of lateral epicondylitis. Furthermore, the results of this study are limited to ambulatory surgery practice patterns in the United States between 1996 and 2006. Last, our ability to perform economic analyses was limited, as data on total hospital cost were not recorded by the surveys.

Conclusion

The increase in ambulatory surgery for lateral epicondylitis, demonstrated in this study, emphasizes the importance of national funding for surveys such as NSAS beyond 2006, as utilization trends may have considerable effects on health care policies that influence the quality of patient care.

First described by Runge¹ in 1873 and later termed lawn-tennis arm by Major² in 1883, lateral epicondylitis is a common cause of elbow pain, affecting 1% to 3% of the general population each year.^3,4 Given that prevalence estimates are up to 15% among workers in repetitive hand task industries,^5-7 symptoms of lateral epicondylitis are thought to be related to recurring wrist extension and alternating forearm pronation and supination.⁸ Between 80% and 90% of patients with lateral epicondylitis experience symptomatic improvement with conservative therapy,^9-11 including rest and use of nonsteroidal anti-inflammatory medications,¹² physical therapy,^13,14 corticosteroid injections,^10,15,16 orthoses,^17,18 and shock wave therapy.¹⁹ However, between 4% and 11% of patients with newly diagnosed lateral epicondylitis do not respond to prolonged (6- to 12-month) conservative treatment and then require operative intervention,^11,20,21 with some referral practices reporting rates as high as 25%.²²

Traditionally, operative management of lateral epicondylitis involved open débridement of the extensor carpi radialis brevis (ECRB).^11,20 More recently, the spectrum of operations for lateral epicondylitis has expanded to include procedures that repair the extensor origin after débridement of the torn tendon and angiofibroblastic dysplasia; procedures that use fasciotomy or direct release of the extensor origin from the epicondyle to relieve tension on the common extensor; procedures directed at the radial or posterior interosseous nerve; and procedures that use arthroscopic techniques to divide the orbicular ligament, reshape the radial head, or release the extensor origin.²³ There has been debate about the value of repairing the ECRB, lengthening the ECRB, simultaneously decompressing the radial nerve or resecting epicondylar bone, and performing the procedures percutaneously, endoscopically, or arthroscopically.^24-28 Despite multiple studies of the outcomes of these procedures,^11,29-31 little is known regarding US national trends for operative treatment of lateral epicondylitis. Understanding national practice patterns and disease burden is essential to allocation of limited health care resources.

We conducted a study to determine US national trends in use of ambulatory surgery for lateral epicondylitis. We focused on age, sex, surgical setting, anesthetic type, and payment method.

Methods

As the National Survey of Ambulatory Surgery³² (NSAS) is an administrative dataset in which all data are deidentified and available for public use, this study was exempt from requiring institutional review board approval.

NSAS data were used to analyze trends in treatment of lateral epicondylitis between 1994 and 2006. NSAS was undertaken by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC) to obtain information about the use of ambulatory surgery in the United States. Since the early 1980s, ambulatory surgery has increased in the United States because of advances in medical technology and cost-containment initiatives.³³ The number of procedures being performed in ambulatory surgery centers increased from 31.5 million in 1996 to 53.3 million in 2006.³⁴ Funded by the CDC, NSAS is a national study that involves both hospital-based and freestanding ambulatory surgery centers and provides the most recent and comprehensive overview of ambulatory surgery in the United States.³⁵ Because of budgetary limitations, 2006 was the last year in which data for NSAS were collected. Data for NSAS come from Medicare-participating, noninstitutional hospitals (excluding military hospitals, federal facilities, and Veteran Affairs hospitals) in all 50 states and the District of Columbia with a minimum of 6 beds staffed for patient use. NSAS used only short-stay hospitals (hospitals with an average length of stay for all patients of less than 30 days) or hospitals that had a specialty of general (medical or surgical) or children’s general. NSAS was conducted in 1994, 1996, and 2006 with medical information recorded on patient abstracts coded by contract staff. NSAS selected a sample of ambulatory surgery visits using a systematic random sampling procedure, and selection of visits within each facility was done separately for each location where ambulatory surgery was performed. In 1994, 751 facilities were sampled, and 88% of hospitals responded. In 1996, 750 facilities were sampled, and 91% of hospitals responded. In 2006, 696 facilities were sampled, and 75% responded. The surveys used International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes³⁶ to classify medical diagnoses and procedures. To produce an unbiased national estimate, NCHS used multistage estimate procedures, including inflation by reciprocals of the probabilities of sample selection, population-weighting ratio adjustments, and adjustment for no response.³⁷

Demographic and medical information was obtained for people with an ICD-9-CM diagnosis code of lateral epicondylitis (726.32), using previously described techniques.³⁸ Data were then recorded for age, sex, facility type, insurance type, anesthesia type, diagnoses, and procedures.

Descriptive statistics consisted of means and standard deviations for continuous variables and frequency and percentages for discrete variables. Because NSAS data were collected on the basis of a probabilistic sample scheme, they were analyzed using a sampling weighting method. Sampling weights (inverse of selection probability) provided by the CDC were used to account for unequal sampling probabilities and to produce estimates for all visits in the United States. A Taylor linearization model provided by the CDC estimates was used to calculate standard error and confidence intervals (CIs) of the data. Standard error is a measure of sampling variability that occurs by chance because only a sample rather than the entire universe is surveyed. To define population parameters, NCHS chose 95% CIs along with a point estimate. Direct statistical comparison between years cannot be performed because of sampling differences in the database compared between years. The CIs, however, can suggest statistical differences if the data are nonoverlapping. US census data were used to obtain national population estimates for each year of the study (1994, 1996, 2006).³⁹ Rates were presented as number of procedures per 100,000 standard population. For age, a direct adjustment procedure was used, and the US population in 2000 was selected as the standard population. Applying sex-specific rates to the standard population and dividing by the total in the standard population, we calculated sex-adjusted rates for each year. All data were analyzed using SPSS Version 20 software.

Results

A total of 30,311 ambulatory surgical procedures (95% CI, 27,292-33,330) or 10.44 per 100,000 capita were recorded by NSAS for the treatment of lateral epicondylitis in 2006 (Table 1). This represents a large increase in the total number of ambulatory procedures, from 21,852 in 1994 (95% CI, 19,981-23,722; 7.29/100,000) and 20,372 in 1996 (95% CI, 18,660-22,083; 6.73/100,000).

Between 1994 and 2006, the sex-adjusted rate of ambulatory surgery for lateral epicondylitis increased by 85% among females (7.74/100,000 to 14.31/100,000), whereas the rate decreased by 31% among males (8.07/100,000 to 5.59/100,000) (Table 1). The age-adjusted rate of ambulatory surgery for lateral epicondylitis increased among all age groups except the 30–39 years group (Table 2). The largest increase in age-adjusted rates was found for patients older than 50 years (275%) between 1994 and 2006.

During the study period, use of regional anesthesia nearly doubled, from 17% to 30%, whereas use of general anesthesia decreased, from 69% to 57% (Table 3). At all time points, the most common procedure performed for lateral epicondylitis in ambulatory surgery centers was division/release of the joint capsule of the elbow (Table 4). Private insurance remained the most common source of payment for all study years, ranging from 52% to 60% (Table 5). The Figure shows that, between 1994 and 2006, the proportion of surgeries performed in a freestanding ambulatory center increased.

Discussion

In this descriptive epidemiologic study, we used NSAS data to investigate trends in ambulatory surgery for lateral epicondylitis between 1994 and 2006.³² Our results showed that total number of procedures and the population-adjusted rate of procedures for lateral epicondylitis increased during the study period. The largest increase in age-adjusted rates of surgery for lateral epicondylitis was found among patients older than 50 years, whereas the highest age-adjusted rate of ambulatory surgery for lateral epicondylitis was found among patients between ages 40 and 49 years. These findings are similar to those of previous studies, which have shown that most patients with lateral epicondylitis present in the fourth and fifth decades of life.²² Prior reports have suggested that the incidence of lateral epicondylitis in men and women is equal.²² The present study found a change in sex-adjusted rates of ambulatory surgery for lateral epicondylitis between 1994 and 2006. Specifically, in 1994, surgery rates for men and women were similar (8.07/100,000 and 7.74/100,000), but in 2006 the sex-adjusted rate of surgery for lateral epicondylitis was almost 3 times higher for women than for men (14.31/100,000 vs 5.59/100,000).

We also found that the population-adjusted rate of lateral epicondylectomy increased drastically, from 0.4 per 100,000 in 1994 to 3.53 per 100,000 in 2006. Lateral epicondylectomy involves excision of the tip of the lateral epicondyle (typically, 0.5 cm) to produce a cancellous bone surface to which the edges of the débrided extensor tendon can be approximated without tension.²³ It is possible that the increased rate of lateral epicondylectomy reflects evidence-based practice changes during the study period,²⁷ though denervation was found more favorable than epicondylectomy in a recent study by Berry and colleagues.⁴⁰ Future studies should investigate whether rates of epicondylectomy have changed since 2006. In addition, the present study showed a correlation between the introduction of arthroscopic techniques for the treatment of lateral epicondylitis and the period when much research was being conducted on the topic.^24,25,28 As arthroscopic techniques improve, their rates are likely to continue to increase.

Our results also showed an increase in procedures performed in freestanding facilities. The rise in ambulatory surgical volume, speculated to result from more procedures being performed in freestanding facilities,³⁴ has been reported with knee and shoulder arthroscopy.⁴¹ In addition, though general anesthesia remained the most used technique, our results showed a shift toward peripheral nerve blocks. The increase in regional anesthesia, which has also been noted in joint arthroscopy, is thought to stem from the advent of nerve-localizing technology, such as nerve stimulation and ultrasound guidance.⁴¹ Peripheral nerve blocks are favorable on both economic and quality measures, are associated with fewer opioid-related side effects, and overall provide better analgesia in comparison with opioids, highlighting their importance in the ambulatory setting.⁴²

Although large, national databases are well suited to epidemiologic research,⁴³ our study had limitations. As with all databases, NSAS is subject to data entry errors and coding errors.^44,45 However, the database administrators corrected for this by using a multistage estimate procedure with weighting adjustments for no response and population-weighting ratio adjustments.³⁵ Another limitation of this study is its lack of clinical detail, as procedure codes are general and do not allow differentiation between specific patients. Because of the retrospective nature of the analysis and the heterogeneity of the data, assessment of specific surgeries for lateral epicondylitis was limited. Although a strength of using NSAS to perform epidemiologic analyses is its large sample size, this also sacrifices specificity in terms of clinical insight. The results of this study may influence investigations to distinguish differences between procedures used in the treatment of lateral epicondylitis. Furthermore, the results of this study are limited to ambulatory surgery practice patterns in the United States between 1996 and 2006. Last, our ability to perform economic analyses was limited, as data on total hospital cost were not recorded by the surveys.

Conclusion

The increase in ambulatory surgery for lateral epicondylitis, demonstrated in this study, emphasizes the importance of national funding for surveys such as NSAS beyond 2006, as utilization trends may have considerable effects on health care policies that influence the quality of patient care.

First described by Runge¹ in 1873 and later termed lawn-tennis arm by Major² in 1883, lateral epicondylitis is a common cause of elbow pain, affecting 1% to 3% of the general population each year.^3,4 Given that prevalence estimates are up to 15% among workers in repetitive hand task industries,^5-7 symptoms of lateral epicondylitis are thought to be related to recurring wrist extension and alternating forearm pronation and supination.⁸ Between 80% and 90% of patients with lateral epicondylitis experience symptomatic improvement with conservative therapy,^9-11 including rest and use of nonsteroidal anti-inflammatory medications,¹² physical therapy,^13,14 corticosteroid injections,^10,15,16 orthoses,^17,18 and shock wave therapy.¹⁹ However, between 4% and 11% of patients with newly diagnosed lateral epicondylitis do not respond to prolonged (6- to 12-month) conservative treatment and then require operative intervention,^11,20,21 with some referral practices reporting rates as high as 25%.²²

Traditionally, operative management of lateral epicondylitis involved open débridement of the extensor carpi radialis brevis (ECRB).^11,20 More recently, the spectrum of operations for lateral epicondylitis has expanded to include procedures that repair the extensor origin after débridement of the torn tendon and angiofibroblastic dysplasia; procedures that use fasciotomy or direct release of the extensor origin from the epicondyle to relieve tension on the common extensor; procedures directed at the radial or posterior interosseous nerve; and procedures that use arthroscopic techniques to divide the orbicular ligament, reshape the radial head, or release the extensor origin.²³ There has been debate about the value of repairing the ECRB, lengthening the ECRB, simultaneously decompressing the radial nerve or resecting epicondylar bone, and performing the procedures percutaneously, endoscopically, or arthroscopically.^24-28 Despite multiple studies of the outcomes of these procedures,^11,29-31 little is known regarding US national trends for operative treatment of lateral epicondylitis. Understanding national practice patterns and disease burden is essential to allocation of limited health care resources.

We conducted a study to determine US national trends in use of ambulatory surgery for lateral epicondylitis. We focused on age, sex, surgical setting, anesthetic type, and payment method.

Methods

As the National Survey of Ambulatory Surgery³² (NSAS) is an administrative dataset in which all data are deidentified and available for public use, this study was exempt from requiring institutional review board approval.

NSAS data were used to analyze trends in treatment of lateral epicondylitis between 1994 and 2006. NSAS was undertaken by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC) to obtain information about the use of ambulatory surgery in the United States. Since the early 1980s, ambulatory surgery has increased in the United States because of advances in medical technology and cost-containment initiatives.³³ The number of procedures being performed in ambulatory surgery centers increased from 31.5 million in 1996 to 53.3 million in 2006.³⁴ Funded by the CDC, NSAS is a national study that involves both hospital-based and freestanding ambulatory surgery centers and provides the most recent and comprehensive overview of ambulatory surgery in the United States.³⁵ Because of budgetary limitations, 2006 was the last year in which data for NSAS were collected. Data for NSAS come from Medicare-participating, noninstitutional hospitals (excluding military hospitals, federal facilities, and Veteran Affairs hospitals) in all 50 states and the District of Columbia with a minimum of 6 beds staffed for patient use. NSAS used only short-stay hospitals (hospitals with an average length of stay for all patients of less than 30 days) or hospitals that had a specialty of general (medical or surgical) or children’s general. NSAS was conducted in 1994, 1996, and 2006 with medical information recorded on patient abstracts coded by contract staff. NSAS selected a sample of ambulatory surgery visits using a systematic random sampling procedure, and selection of visits within each facility was done separately for each location where ambulatory surgery was performed. In 1994, 751 facilities were sampled, and 88% of hospitals responded. In 1996, 750 facilities were sampled, and 91% of hospitals responded. In 2006, 696 facilities were sampled, and 75% responded. The surveys used International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes³⁶ to classify medical diagnoses and procedures. To produce an unbiased national estimate, NCHS used multistage estimate procedures, including inflation by reciprocals of the probabilities of sample selection, population-weighting ratio adjustments, and adjustment for no response.³⁷

Demographic and medical information was obtained for people with an ICD-9-CM diagnosis code of lateral epicondylitis (726.32), using previously described techniques.³⁸ Data were then recorded for age, sex, facility type, insurance type, anesthesia type, diagnoses, and procedures.

Descriptive statistics consisted of means and standard deviations for continuous variables and frequency and percentages for discrete variables. Because NSAS data were collected on the basis of a probabilistic sample scheme, they were analyzed using a sampling weighting method. Sampling weights (inverse of selection probability) provided by the CDC were used to account for unequal sampling probabilities and to produce estimates for all visits in the United States. A Taylor linearization model provided by the CDC estimates was used to calculate standard error and confidence intervals (CIs) of the data. Standard error is a measure of sampling variability that occurs by chance because only a sample rather than the entire universe is surveyed. To define population parameters, NCHS chose 95% CIs along with a point estimate. Direct statistical comparison between years cannot be performed because of sampling differences in the database compared between years. The CIs, however, can suggest statistical differences if the data are nonoverlapping. US census data were used to obtain national population estimates for each year of the study (1994, 1996, 2006).³⁹ Rates were presented as number of procedures per 100,000 standard population. For age, a direct adjustment procedure was used, and the US population in 2000 was selected as the standard population. Applying sex-specific rates to the standard population and dividing by the total in the standard population, we calculated sex-adjusted rates for each year. All data were analyzed using SPSS Version 20 software.

Results

A total of 30,311 ambulatory surgical procedures (95% CI, 27,292-33,330) or 10.44 per 100,000 capita were recorded by NSAS for the treatment of lateral epicondylitis in 2006 (Table 1). This represents a large increase in the total number of ambulatory procedures, from 21,852 in 1994 (95% CI, 19,981-23,722; 7.29/100,000) and 20,372 in 1996 (95% CI, 18,660-22,083; 6.73/100,000).

Between 1994 and 2006, the sex-adjusted rate of ambulatory surgery for lateral epicondylitis increased by 85% among females (7.74/100,000 to 14.31/100,000), whereas the rate decreased by 31% among males (8.07/100,000 to 5.59/100,000) (Table 1). The age-adjusted rate of ambulatory surgery for lateral epicondylitis increased among all age groups except the 30–39 years group (Table 2). The largest increase in age-adjusted rates was found for patients older than 50 years (275%) between 1994 and 2006.

During the study period, use of regional anesthesia nearly doubled, from 17% to 30%, whereas use of general anesthesia decreased, from 69% to 57% (Table 3). At all time points, the most common procedure performed for lateral epicondylitis in ambulatory surgery centers was division/release of the joint capsule of the elbow (Table 4). Private insurance remained the most common source of payment for all study years, ranging from 52% to 60% (Table 5). The Figure shows that, between 1994 and 2006, the proportion of surgeries performed in a freestanding ambulatory center increased.

Discussion

In this descriptive epidemiologic study, we used NSAS data to investigate trends in ambulatory surgery for lateral epicondylitis between 1994 and 2006.³² Our results showed that total number of procedures and the population-adjusted rate of procedures for lateral epicondylitis increased during the study period. The largest increase in age-adjusted rates of surgery for lateral epicondylitis was found among patients older than 50 years, whereas the highest age-adjusted rate of ambulatory surgery for lateral epicondylitis was found among patients between ages 40 and 49 years. These findings are similar to those of previous studies, which have shown that most patients with lateral epicondylitis present in the fourth and fifth decades of life.²² Prior reports have suggested that the incidence of lateral epicondylitis in men and women is equal.²² The present study found a change in sex-adjusted rates of ambulatory surgery for lateral epicondylitis between 1994 and 2006. Specifically, in 1994, surgery rates for men and women were similar (8.07/100,000 and 7.74/100,000), but in 2006 the sex-adjusted rate of surgery for lateral epicondylitis was almost 3 times higher for women than for men (14.31/100,000 vs 5.59/100,000).

We also found that the population-adjusted rate of lateral epicondylectomy increased drastically, from 0.4 per 100,000 in 1994 to 3.53 per 100,000 in 2006. Lateral epicondylectomy involves excision of the tip of the lateral epicondyle (typically, 0.5 cm) to produce a cancellous bone surface to which the edges of the débrided extensor tendon can be approximated without tension.²³ It is possible that the increased rate of lateral epicondylectomy reflects evidence-based practice changes during the study period,²⁷ though denervation was found more favorable than epicondylectomy in a recent study by Berry and colleagues.⁴⁰ Future studies should investigate whether rates of epicondylectomy have changed since 2006. In addition, the present study showed a correlation between the introduction of arthroscopic techniques for the treatment of lateral epicondylitis and the period when much research was being conducted on the topic.^24,25,28 As arthroscopic techniques improve, their rates are likely to continue to increase.

Our results also showed an increase in procedures performed in freestanding facilities. The rise in ambulatory surgical volume, speculated to result from more procedures being performed in freestanding facilities,³⁴ has been reported with knee and shoulder arthroscopy.⁴¹ In addition, though general anesthesia remained the most used technique, our results showed a shift toward peripheral nerve blocks. The increase in regional anesthesia, which has also been noted in joint arthroscopy, is thought to stem from the advent of nerve-localizing technology, such as nerve stimulation and ultrasound guidance.⁴¹ Peripheral nerve blocks are favorable on both economic and quality measures, are associated with fewer opioid-related side effects, and overall provide better analgesia in comparison with opioids, highlighting their importance in the ambulatory setting.⁴²

Although large, national databases are well suited to epidemiologic research,⁴³ our study had limitations. As with all databases, NSAS is subject to data entry errors and coding errors.^44,45 However, the database administrators corrected for this by using a multistage estimate procedure with weighting adjustments for no response and population-weighting ratio adjustments.³⁵ Another limitation of this study is its lack of clinical detail, as procedure codes are general and do not allow differentiation between specific patients. Because of the retrospective nature of the analysis and the heterogeneity of the data, assessment of specific surgeries for lateral epicondylitis was limited. Although a strength of using NSAS to perform epidemiologic analyses is its large sample size, this also sacrifices specificity in terms of clinical insight. The results of this study may influence investigations to distinguish differences between procedures used in the treatment of lateral epicondylitis. Furthermore, the results of this study are limited to ambulatory surgery practice patterns in the United States between 1996 and 2006. Last, our ability to perform economic analyses was limited, as data on total hospital cost were not recorded by the surveys.

Conclusion

The increase in ambulatory surgery for lateral epicondylitis, demonstrated in this study, emphasizes the importance of national funding for surveys such as NSAS beyond 2006, as utilization trends may have considerable effects on health care policies that influence the quality of patient care.

Chronic hemophilic arthropathy, a well-known complication of hemophilia, develops as a long-term consequence of recurrent joint bleeds resulting in synovial hypertrophy (chronic proliferative synovitis) and joint cartilage destruction. Hemophilic arthropathy mostly affects the knees, ankles, and elbows and causes chronic joint pain and functional impairment in relatively young patients who have not received adequate primary prophylactic replacement therapy with factor concentrates from early childhood.^1-3

In the late stages of hemophilic arthropathy of the knee, total knee arthroplasty (TKA) provides dramatic joint pain relief, improves knee functional status, and reduces rebleeding into the joint.^4-8 TKA performed on a patient with hemophilia was first reported in the mid-1970s.^9,10 In these cases, the surgical procedure itself is often complicated by severe fibrosis developing in the joint soft tissues, flexion joint contracture, and poor quality of the joint bone structures. Even though TKA significantly reduces joint pain in patients with chronic hemophilic arthropathy, some authors have achieved only modest functional outcomes and experienced a high rate of complications (infection, prosthetic loosening).^11-13 Data on TKA outcomes are still scarce, and most studies have enrolled a limited number of patients.

We retrospectively evaluated the outcomes of 88 primary TKAs performed on patients with severe hemophilia at a single institution. Clinical outcomes and complications were assessed with a special focus on prosthetic survival and infection.

Patients and Methods

Ninety-one primary TKAs were performed in 77 patients with severe hemophilia A and B (factor VIII [FVIII] and factor IX plasma concentration, <1% each) between January 1, 1999, and December 31, 2011, and the medical records of all these patients were thoroughly reviewed in 2013. The cases of 3 patients who died shortly after surgery were excluded from analysis. Thus, 88 TKAs and 74 patients (74 males) were finally available for evaluation. Fourteen patients underwent bilateral TKAs but none concurrently. The patients provided written informed consent for print and electronic publication of their outcomes.

We recorded demographic data, type and severity of hemophilia, human immunodeficiency virus (HIV) status, hepatitis C virus (HCV) status, and Knee Society Scale (KSS) scores.¹⁴ KSS scores include Knee score (pain, range of motion [ROM], stability) and Function score (walking, stairs), both of which range from 0 (normal knee) to 100 (most affected knee). Prosthetic infection was classified (Segawa and colleagues¹⁵) as early or late, depending on timing of symptom onset (4 weeks after replacement surgery was the threshold used).

Patients received an intravenous bolus infusion of the deficient factor concentrate followed by continuous infusion to reach a plasma factor level of 100% just before surgery and during the first 7 postoperative days and 50% over the next 7 days (Table 1). Patients with a circulating inhibitor (3 overall) received bypassing agents FEIBA (FVIII inhibitor bypassing agent) or rFVIIa (recombinant factor VII activated) (Table 2). Patients were not given any antifibrinolytic treatment or thromboprophylaxis.

Surgery was performed in a standard surgical room. Patients were placed on the operating table in decubitus supinus position. A parapatellar medial incision was made on a bloodless surgical field (achieved with tourniquet ischemia). The prosthesis model used was always the cemented (gentamicin bone cement) NexGen (Zimmer). Patellar resurfacing was done in all cases (Figures 1A–1D). All TKAs were performed by Dr. Rodríguez-Merchán. Intravenous antibiotic prophylaxis was administered at anesthetic induction and during the first 48 hours after surgery (3 further doses). Active exercises were started on postoperative day 1. Joint load aided with 2 crutches was allowed starting on postoperative day 2.

Mean patient age was 38.2 years (range, 24-73 years). Of the 74 patients, 55 had a diagnosis of severe hemophilia A, and 19 had a diagnosis of severe hemophilia B. During the follow-up period, 23 patients died (mean time, 6.4 years; range, 4-9 years). Causes of death were acquired immune deficiency syndrome (AIDS), liver cirrhosis, and intracranial bleeding. Mean follow-up for the full series of patients was 8 years (range, 1-13 years).

Descriptive statistical analysis was performed with SPSS Windows Version 18.0. Prosthetic failure was regarded as implant removal for any reason. Student t test was used to compare continuous variables, and either χ² test or Fisher exact test was used to compare categorical variables. P < .05 (2-sided) was considered significant.

Results

Prosthetic survival rates with implant removal for any reason regarded as final endpoint was 92%. Causes of failure were prosthetic infection (6 cases, 6.8%) and loosening (2 cases, 2.2%). Of the 6 prosthetic infections, 5 were regarded as late and 1 as early. Late infections were successfully sorted by performing 2-stage revision TKA with the Constrained Condylar Knee (Zimmer). Acute infections were managed by open joint débridement and polyethylene exchange. Both cases of aseptic loosening of the TKA were successfully managed with 1-stage revision TKA using the same implant model (Figures 2A–2D).

Mean KSS Knee score improved from 79 before surgery to 36 after surgery, and mean KSS Function score improved from 63 to 33. KSS Pain score, which is included in the Knee score, 0 (no pain) to 50 (most severe pain), improved from 47 to 8. Patients receiving inhibitors and patients who were HIV- or HCV-positive did not have poorer outcomes relative to those of patients not receiving inhibitors and patients who were HIV- or HCV-negative. Patients with liver cirrhosis had a lower prosthetic survival rate and lower Knee scores.

Discussion

The prosthetic survival rate found in this study compares well with other reported rates for patients with hemophilia and other bleeding disorders. However, evidence regarding long-term prosthesis survival in TKAs performed for patients with hemophilia is limited. Table 3 summarizes the main reported series of patients with hemophilia with 10-year prosthetic survival rates, number of TKAs performed, and mean follow-up period; in all these series, implant removal for any reason was regarded as the final endpoint.^5-8,16,17 Mean follow-up in our study was 8 years. Clinical outcomes of TKA in patients with severe hemophilia and related disorders are expected to be inferior to those achieved in patients without a bleeding condition. The overall 10-year prosthetic survival rate for cemented TKA implants, as reported by the Norwegian Arthroplasty Register, was on the order of 93%.¹⁸ Mean age of our patients at time of surgery was only 38.2 years. TKAs performed in younger patients without a bleeding disorder have been associated with shorter implant survival times relative to those of elderly patients.¹⁹ Thus, Diduch and colleagues²⁰ reported a prosthetic survival rate of 87% at 18 years in 108 TKAs performed on patients under age 55 years. Lonner and colleagues²¹ reported a better implant survival rate (90% at 8 years) in a series of patients under age 40 years (32 TKAs). In a study by Duffy and colleagues,²² the implant survival rate was 85% at 15 years in patients under age 55 years (74 TKAs). The results from our retrospective case assessment are quite similar to the overall prosthetic survival rates reported for TKAs performed on patients without hemophilia.

Rates of periprosthetic infection after primary TKA in patients with hemophilia and other bleeding conditions are much higher (up to 11%), with a mean infection rate of 6.2% (range, 1% to 11%), consistent with the rate found in our series of patients (6.8%)^{7,16,17,23,24} (Table 4). This rate is much higher than that reported after primary TKA in patients without hemophilia but is similar to some rates reported for patients with hemophilia. In our experience, most periprosthetic infections (5/6) were sorted as late.

Late infection is a major concern after TKA in patients with hemophilia, and various factors have been hypothesized as contributing to the high prevalence. An important factor is the high rate of HIV-positive patients among patients with hemophilia—which acts as a strong predisposing factor because of the often low CD4 counts and associated immune deficiency,²⁵ but different reports have provided conflicting results in this respect.^5,6,12 We found no relationship between HIV status and risk for periprosthetic infection, but conclusions are limited by the low number of HIV-positive patients in our series (14/74, 18.9%). Our patients’ late periprosthetic infections were diagnosed several years after TKA, suggesting hematogenous spread of infection. Most of these patients either were on regular prophylactic factor infusions or were being treated on demand, which might entail a risk for contamination of infusions by skin bacteria from the puncture site. Therefore, having an aseptic technique for administering coagulation factor concentrates is of paramount importance for patients with hemophilia and a knee implant.

Another important complication of TKA surgery is aseptic loosening of the prosthesis. Aseptic loosening occurred in 2.2% of our patients, but higher rates have been reported elsewhere.^11,26 Rates of this complication increase over follow-up, and some authors have linked this complication to TKA polyethylene wear.²⁷ Development of a reactive and destructive bone–cement interface and microhemorrhages into such interface might be implicated in the higher rate of loosening observed among patients with hemophilia.²⁸

In the present study, preoperative and postoperative functional outcomes differed significantly. A modest postoperative total ROM of 69º to 79º has been reported by several authors.^5,6 Postoperative ROM may vary—may be slightly increased, remain unchanged, or may even be reduced.^4,23,26 Even though little improvement in total ROM is achieved after TKA, many authors have reported reduced flexion contracture and hence an easier gait. However, along with functional improvement, dramatic pain relief after TKA is perhaps the most remarkable aspect, and it has a strong effect on patient satisfaction after surgery.^5,7,8,18,23

Our study had 2 main limitations. First, it was a retrospective case series evaluation with the usual issues of potential inaccuracy of medical records and information bias. Second, the study did not include a control group.

Conclusion

The primary TKAs performed in our patients with hemophilia have had a good prosthetic survival rate. Even though such a result is slightly inferior to results in patients without hemophilia, our prosthetic survival rate is not significantly different from the rates reported in other, younger patient subsets. Late periprosthetic infections are a major concern, and taking precautions to avoid hematogenous spread of infections during factor concentrate infusions is strongly encouraged.

Chronic hemophilic arthropathy, a well-known complication of hemophilia, develops as a long-term consequence of recurrent joint bleeds resulting in synovial hypertrophy (chronic proliferative synovitis) and joint cartilage destruction. Hemophilic arthropathy mostly affects the knees, ankles, and elbows and causes chronic joint pain and functional impairment in relatively young patients who have not received adequate primary prophylactic replacement therapy with factor concentrates from early childhood.^1-3

In the late stages of hemophilic arthropathy of the knee, total knee arthroplasty (TKA) provides dramatic joint pain relief, improves knee functional status, and reduces rebleeding into the joint.^4-8 TKA performed on a patient with hemophilia was first reported in the mid-1970s.^9,10 In these cases, the surgical procedure itself is often complicated by severe fibrosis developing in the joint soft tissues, flexion joint contracture, and poor quality of the joint bone structures. Even though TKA significantly reduces joint pain in patients with chronic hemophilic arthropathy, some authors have achieved only modest functional outcomes and experienced a high rate of complications (infection, prosthetic loosening).^11-13 Data on TKA outcomes are still scarce, and most studies have enrolled a limited number of patients.

We retrospectively evaluated the outcomes of 88 primary TKAs performed on patients with severe hemophilia at a single institution. Clinical outcomes and complications were assessed with a special focus on prosthetic survival and infection.

Patients and Methods

Ninety-one primary TKAs were performed in 77 patients with severe hemophilia A and B (factor VIII [FVIII] and factor IX plasma concentration, <1% each) between January 1, 1999, and December 31, 2011, and the medical records of all these patients were thoroughly reviewed in 2013. The cases of 3 patients who died shortly after surgery were excluded from analysis. Thus, 88 TKAs and 74 patients (74 males) were finally available for evaluation. Fourteen patients underwent bilateral TKAs but none concurrently. The patients provided written informed consent for print and electronic publication of their outcomes.

We recorded demographic data, type and severity of hemophilia, human immunodeficiency virus (HIV) status, hepatitis C virus (HCV) status, and Knee Society Scale (KSS) scores.¹⁴ KSS scores include Knee score (pain, range of motion [ROM], stability) and Function score (walking, stairs), both of which range from 0 (normal knee) to 100 (most affected knee). Prosthetic infection was classified (Segawa and colleagues¹⁵) as early or late, depending on timing of symptom onset (4 weeks after replacement surgery was the threshold used).

Patients received an intravenous bolus infusion of the deficient factor concentrate followed by continuous infusion to reach a plasma factor level of 100% just before surgery and during the first 7 postoperative days and 50% over the next 7 days (Table 1). Patients with a circulating inhibitor (3 overall) received bypassing agents FEIBA (FVIII inhibitor bypassing agent) or rFVIIa (recombinant factor VII activated) (Table 2). Patients were not given any antifibrinolytic treatment or thromboprophylaxis.

Surgery was performed in a standard surgical room. Patients were placed on the operating table in decubitus supinus position. A parapatellar medial incision was made on a bloodless surgical field (achieved with tourniquet ischemia). The prosthesis model used was always the cemented (gentamicin bone cement) NexGen (Zimmer). Patellar resurfacing was done in all cases (Figures 1A–1D). All TKAs were performed by Dr. Rodríguez-Merchán. Intravenous antibiotic prophylaxis was administered at anesthetic induction and during the first 48 hours after surgery (3 further doses). Active exercises were started on postoperative day 1. Joint load aided with 2 crutches was allowed starting on postoperative day 2.

Mean patient age was 38.2 years (range, 24-73 years). Of the 74 patients, 55 had a diagnosis of severe hemophilia A, and 19 had a diagnosis of severe hemophilia B. During the follow-up period, 23 patients died (mean time, 6.4 years; range, 4-9 years). Causes of death were acquired immune deficiency syndrome (AIDS), liver cirrhosis, and intracranial bleeding. Mean follow-up for the full series of patients was 8 years (range, 1-13 years).

Descriptive statistical analysis was performed with SPSS Windows Version 18.0. Prosthetic failure was regarded as implant removal for any reason. Student t test was used to compare continuous variables, and either χ² test or Fisher exact test was used to compare categorical variables. P < .05 (2-sided) was considered significant.

Results

Prosthetic survival rates with implant removal for any reason regarded as final endpoint was 92%. Causes of failure were prosthetic infection (6 cases, 6.8%) and loosening (2 cases, 2.2%). Of the 6 prosthetic infections, 5 were regarded as late and 1 as early. Late infections were successfully sorted by performing 2-stage revision TKA with the Constrained Condylar Knee (Zimmer). Acute infections were managed by open joint débridement and polyethylene exchange. Both cases of aseptic loosening of the TKA were successfully managed with 1-stage revision TKA using the same implant model (Figures 2A–2D).

Mean KSS Knee score improved from 79 before surgery to 36 after surgery, and mean KSS Function score improved from 63 to 33. KSS Pain score, which is included in the Knee score, 0 (no pain) to 50 (most severe pain), improved from 47 to 8. Patients receiving inhibitors and patients who were HIV- or HCV-positive did not have poorer outcomes relative to those of patients not receiving inhibitors and patients who were HIV- or HCV-negative. Patients with liver cirrhosis had a lower prosthetic survival rate and lower Knee scores.

Discussion

The prosthetic survival rate found in this study compares well with other reported rates for patients with hemophilia and other bleeding disorders. However, evidence regarding long-term prosthesis survival in TKAs performed for patients with hemophilia is limited. Table 3 summarizes the main reported series of patients with hemophilia with 10-year prosthetic survival rates, number of TKAs performed, and mean follow-up period; in all these series, implant removal for any reason was regarded as the final endpoint.^5-8,16,17 Mean follow-up in our study was 8 years. Clinical outcomes of TKA in patients with severe hemophilia and related disorders are expected to be inferior to those achieved in patients without a bleeding condition. The overall 10-year prosthetic survival rate for cemented TKA implants, as reported by the Norwegian Arthroplasty Register, was on the order of 93%.¹⁸ Mean age of our patients at time of surgery was only 38.2 years. TKAs performed in younger patients without a bleeding disorder have been associated with shorter implant survival times relative to those of elderly patients.¹⁹ Thus, Diduch and colleagues²⁰ reported a prosthetic survival rate of 87% at 18 years in 108 TKAs performed on patients under age 55 years. Lonner and colleagues²¹ reported a better implant survival rate (90% at 8 years) in a series of patients under age 40 years (32 TKAs). In a study by Duffy and colleagues,²² the implant survival rate was 85% at 15 years in patients under age 55 years (74 TKAs). The results from our retrospective case assessment are quite similar to the overall prosthetic survival rates reported for TKAs performed on patients without hemophilia.

Rates of periprosthetic infection after primary TKA in patients with hemophilia and other bleeding conditions are much higher (up to 11%), with a mean infection rate of 6.2% (range, 1% to 11%), consistent with the rate found in our series of patients (6.8%)^{7,16,17,23,24} (Table 4). This rate is much higher than that reported after primary TKA in patients without hemophilia but is similar to some rates reported for patients with hemophilia. In our experience, most periprosthetic infections (5/6) were sorted as late.

Late infection is a major concern after TKA in patients with hemophilia, and various factors have been hypothesized as contributing to the high prevalence. An important factor is the high rate of HIV-positive patients among patients with hemophilia—which acts as a strong predisposing factor because of the often low CD4 counts and associated immune deficiency,²⁵ but different reports have provided conflicting results in this respect.^5,6,12 We found no relationship between HIV status and risk for periprosthetic infection, but conclusions are limited by the low number of HIV-positive patients in our series (14/74, 18.9%). Our patients’ late periprosthetic infections were diagnosed several years after TKA, suggesting hematogenous spread of infection. Most of these patients either were on regular prophylactic factor infusions or were being treated on demand, which might entail a risk for contamination of infusions by skin bacteria from the puncture site. Therefore, having an aseptic technique for administering coagulation factor concentrates is of paramount importance for patients with hemophilia and a knee implant.

Another important complication of TKA surgery is aseptic loosening of the prosthesis. Aseptic loosening occurred in 2.2% of our patients, but higher rates have been reported elsewhere.^11,26 Rates of this complication increase over follow-up, and some authors have linked this complication to TKA polyethylene wear.²⁷ Development of a reactive and destructive bone–cement interface and microhemorrhages into such interface might be implicated in the higher rate of loosening observed among patients with hemophilia.²⁸

In the present study, preoperative and postoperative functional outcomes differed significantly. A modest postoperative total ROM of 69º to 79º has been reported by several authors.^5,6 Postoperative ROM may vary—may be slightly increased, remain unchanged, or may even be reduced.^4,23,26 Even though little improvement in total ROM is achieved after TKA, many authors have reported reduced flexion contracture and hence an easier gait. However, along with functional improvement, dramatic pain relief after TKA is perhaps the most remarkable aspect, and it has a strong effect on patient satisfaction after surgery.^5,7,8,18,23

Our study had 2 main limitations. First, it was a retrospective case series evaluation with the usual issues of potential inaccuracy of medical records and information bias. Second, the study did not include a control group.

Conclusion

The primary TKAs performed in our patients with hemophilia have had a good prosthetic survival rate. Even though such a result is slightly inferior to results in patients without hemophilia, our prosthetic survival rate is not significantly different from the rates reported in other, younger patient subsets. Late periprosthetic infections are a major concern, and taking precautions to avoid hematogenous spread of infections during factor concentrate infusions is strongly encouraged.

Chronic hemophilic arthropathy, a well-known complication of hemophilia, develops as a long-term consequence of recurrent joint bleeds resulting in synovial hypertrophy (chronic proliferative synovitis) and joint cartilage destruction. Hemophilic arthropathy mostly affects the knees, ankles, and elbows and causes chronic joint pain and functional impairment in relatively young patients who have not received adequate primary prophylactic replacement therapy with factor concentrates from early childhood.^1-3

In the late stages of hemophilic arthropathy of the knee, total knee arthroplasty (TKA) provides dramatic joint pain relief, improves knee functional status, and reduces rebleeding into the joint.^4-8 TKA performed on a patient with hemophilia was first reported in the mid-1970s.^9,10 In these cases, the surgical procedure itself is often complicated by severe fibrosis developing in the joint soft tissues, flexion joint contracture, and poor quality of the joint bone structures. Even though TKA significantly reduces joint pain in patients with chronic hemophilic arthropathy, some authors have achieved only modest functional outcomes and experienced a high rate of complications (infection, prosthetic loosening).^11-13 Data on TKA outcomes are still scarce, and most studies have enrolled a limited number of patients.

We retrospectively evaluated the outcomes of 88 primary TKAs performed on patients with severe hemophilia at a single institution. Clinical outcomes and complications were assessed with a special focus on prosthetic survival and infection.

Patients and Methods

Ninety-one primary TKAs were performed in 77 patients with severe hemophilia A and B (factor VIII [FVIII] and factor IX plasma concentration, <1% each) between January 1, 1999, and December 31, 2011, and the medical records of all these patients were thoroughly reviewed in 2013. The cases of 3 patients who died shortly after surgery were excluded from analysis. Thus, 88 TKAs and 74 patients (74 males) were finally available for evaluation. Fourteen patients underwent bilateral TKAs but none concurrently. The patients provided written informed consent for print and electronic publication of their outcomes.

We recorded demographic data, type and severity of hemophilia, human immunodeficiency virus (HIV) status, hepatitis C virus (HCV) status, and Knee Society Scale (KSS) scores.¹⁴ KSS scores include Knee score (pain, range of motion [ROM], stability) and Function score (walking, stairs), both of which range from 0 (normal knee) to 100 (most affected knee). Prosthetic infection was classified (Segawa and colleagues¹⁵) as early or late, depending on timing of symptom onset (4 weeks after replacement surgery was the threshold used).

Patients received an intravenous bolus infusion of the deficient factor concentrate followed by continuous infusion to reach a plasma factor level of 100% just before surgery and during the first 7 postoperative days and 50% over the next 7 days (Table 1). Patients with a circulating inhibitor (3 overall) received bypassing agents FEIBA (FVIII inhibitor bypassing agent) or rFVIIa (recombinant factor VII activated) (Table 2). Patients were not given any antifibrinolytic treatment or thromboprophylaxis.

Surgery was performed in a standard surgical room. Patients were placed on the operating table in decubitus supinus position. A parapatellar medial incision was made on a bloodless surgical field (achieved with tourniquet ischemia). The prosthesis model used was always the cemented (gentamicin bone cement) NexGen (Zimmer). Patellar resurfacing was done in all cases (Figures 1A–1D). All TKAs were performed by Dr. Rodríguez-Merchán. Intravenous antibiotic prophylaxis was administered at anesthetic induction and during the first 48 hours after surgery (3 further doses). Active exercises were started on postoperative day 1. Joint load aided with 2 crutches was allowed starting on postoperative day 2.

Mean patient age was 38.2 years (range, 24-73 years). Of the 74 patients, 55 had a diagnosis of severe hemophilia A, and 19 had a diagnosis of severe hemophilia B. During the follow-up period, 23 patients died (mean time, 6.4 years; range, 4-9 years). Causes of death were acquired immune deficiency syndrome (AIDS), liver cirrhosis, and intracranial bleeding. Mean follow-up for the full series of patients was 8 years (range, 1-13 years).

Descriptive statistical analysis was performed with SPSS Windows Version 18.0. Prosthetic failure was regarded as implant removal for any reason. Student t test was used to compare continuous variables, and either χ² test or Fisher exact test was used to compare categorical variables. P < .05 (2-sided) was considered significant.

Results

Prosthetic survival rates with implant removal for any reason regarded as final endpoint was 92%. Causes of failure were prosthetic infection (6 cases, 6.8%) and loosening (2 cases, 2.2%). Of the 6 prosthetic infections, 5 were regarded as late and 1 as early. Late infections were successfully sorted by performing 2-stage revision TKA with the Constrained Condylar Knee (Zimmer). Acute infections were managed by open joint débridement and polyethylene exchange. Both cases of aseptic loosening of the TKA were successfully managed with 1-stage revision TKA using the same implant model (Figures 2A–2D).

Mean KSS Knee score improved from 79 before surgery to 36 after surgery, and mean KSS Function score improved from 63 to 33. KSS Pain score, which is included in the Knee score, 0 (no pain) to 50 (most severe pain), improved from 47 to 8. Patients receiving inhibitors and patients who were HIV- or HCV-positive did not have poorer outcomes relative to those of patients not receiving inhibitors and patients who were HIV- or HCV-negative. Patients with liver cirrhosis had a lower prosthetic survival rate and lower Knee scores.

Discussion

The prosthetic survival rate found in this study compares well with other reported rates for patients with hemophilia and other bleeding disorders. However, evidence regarding long-term prosthesis survival in TKAs performed for patients with hemophilia is limited. Table 3 summarizes the main reported series of patients with hemophilia with 10-year prosthetic survival rates, number of TKAs performed, and mean follow-up period; in all these series, implant removal for any reason was regarded as the final endpoint.^5-8,16,17 Mean follow-up in our study was 8 years. Clinical outcomes of TKA in patients with severe hemophilia and related disorders are expected to be inferior to those achieved in patients without a bleeding condition. The overall 10-year prosthetic survival rate for cemented TKA implants, as reported by the Norwegian Arthroplasty Register, was on the order of 93%.¹⁸ Mean age of our patients at time of surgery was only 38.2 years. TKAs performed in younger patients without a bleeding disorder have been associated with shorter implant survival times relative to those of elderly patients.¹⁹ Thus, Diduch and colleagues²⁰ reported a prosthetic survival rate of 87% at 18 years in 108 TKAs performed on patients under age 55 years. Lonner and colleagues²¹ reported a better implant survival rate (90% at 8 years) in a series of patients under age 40 years (32 TKAs). In a study by Duffy and colleagues,²² the implant survival rate was 85% at 15 years in patients under age 55 years (74 TKAs). The results from our retrospective case assessment are quite similar to the overall prosthetic survival rates reported for TKAs performed on patients without hemophilia.

Rates of periprosthetic infection after primary TKA in patients with hemophilia and other bleeding conditions are much higher (up to 11%), with a mean infection rate of 6.2% (range, 1% to 11%), consistent with the rate found in our series of patients (6.8%)^{7,16,17,23,24} (Table 4). This rate is much higher than that reported after primary TKA in patients without hemophilia but is similar to some rates reported for patients with hemophilia. In our experience, most periprosthetic infections (5/6) were sorted as late.

Late infection is a major concern after TKA in patients with hemophilia, and various factors have been hypothesized as contributing to the high prevalence. An important factor is the high rate of HIV-positive patients among patients with hemophilia—which acts as a strong predisposing factor because of the often low CD4 counts and associated immune deficiency,²⁵ but different reports have provided conflicting results in this respect.^5,6,12 We found no relationship between HIV status and risk for periprosthetic infection, but conclusions are limited by the low number of HIV-positive patients in our series (14/74, 18.9%). Our patients’ late periprosthetic infections were diagnosed several years after TKA, suggesting hematogenous spread of infection. Most of these patients either were on regular prophylactic factor infusions or were being treated on demand, which might entail a risk for contamination of infusions by skin bacteria from the puncture site. Therefore, having an aseptic technique for administering coagulation factor concentrates is of paramount importance for patients with hemophilia and a knee implant.

Another important complication of TKA surgery is aseptic loosening of the prosthesis. Aseptic loosening occurred in 2.2% of our patients, but higher rates have been reported elsewhere.^11,26 Rates of this complication increase over follow-up, and some authors have linked this complication to TKA polyethylene wear.²⁷ Development of a reactive and destructive bone–cement interface and microhemorrhages into such interface might be implicated in the higher rate of loosening observed among patients with hemophilia.²⁸

In the present study, preoperative and postoperative functional outcomes differed significantly. A modest postoperative total ROM of 69º to 79º has been reported by several authors.^5,6 Postoperative ROM may vary—may be slightly increased, remain unchanged, or may even be reduced.^4,23,26 Even though little improvement in total ROM is achieved after TKA, many authors have reported reduced flexion contracture and hence an easier gait. However, along with functional improvement, dramatic pain relief after TKA is perhaps the most remarkable aspect, and it has a strong effect on patient satisfaction after surgery.^5,7,8,18,23

Our study had 2 main limitations. First, it was a retrospective case series evaluation with the usual issues of potential inaccuracy of medical records and information bias. Second, the study did not include a control group.

Conclusion

The primary TKAs performed in our patients with hemophilia have had a good prosthetic survival rate. Even though such a result is slightly inferior to results in patients without hemophilia, our prosthetic survival rate is not significantly different from the rates reported in other, younger patient subsets. Late periprosthetic infections are a major concern, and taking precautions to avoid hematogenous spread of infections during factor concentrate infusions is strongly encouraged.