Perioperative Medicine

CHICAGO – Performing rapid thromboelastography on admission can help trauma surgeons determine which patients are at greatest risk of developing pulmonary embolism, judging by results of a study of more than 8,000 patients.

The incidence of pulmonary embolism (PE), although still below 0.5%, has more than doubled in recent years, according to a recent report using data from the National Trauma Data Bank (Ann. Surg. 2011 Aug. 24 [E-pub ahead of print]).

"Despite this increasing knowledge of risk factors, despite increasing chemoprophylaxis – we’re getting more aggressive with head injuries in starting enoxaparin and heparin, and more aggressive with our spine and solid organ injuries – despite all this, the incidence of PE is increasing," Dr. Bryan A. Cotton said at the annual meeting of the American Association for the Surgery of Trauma.

To learn whether rapid thromboelastography (r-TEG), using a maximum amplitude (mA) greater than 65 mm, could identify patients at risk of developing PE during their hospital stay, Dr. Cotton and his colleagues at the University of Texas Health Science Center in Houston evaluated the use of r-TEG upon admission to the trauma bay for 8,330 total trauma patients over an 18-month period.

"Recent data from multiple institutions have shown an increase in vascular complications following these states if the mA values and certain other portions of TEG values are elevated," Dr. Cotton said. Besides PE and venous thromboembolism (VTE), complications including stroke and postoperative MI have been shown to increase with postoperative and postinjury r-TEG values, he added.

In the Houston study, r-TEG was obtained on 2,070 consecutive trauma patients. Of those, 2.5% went on to develop PE. These patients tended to be older and were more likely to be white and more severely injured than the other patients, and to have only blunt injuries.

"We found the admission mA, which is the highest amplitude of the clot, was associated with risk of developing PE during hospital stay," Dr. Cotton said.

The median time to development of PE was 6 days (duration, 2-31 days), he noted. The investigators also analyzed other factors, and when controlling for male sex, Injury Severity Score, and age, they found that an individual with an mA greater than 65 mm at the time of admission had a 3.5-fold greater odds of developing PE during the hospital stay, Dr. Cotton said. When they raised the threshold to an mA of 72 mm or higher, the risk profile increased sixfold, he said.

"An mA of 65 [mm] or greater is just as good as traditionally noted high-risk factors," Dr. Cotton said. "These include pelvic factures and lower extremity spine and head injuries. When mA is greater than 72 [mm], it exceeds or equals the odds ratio for very-high-risk factors such as prolonged ventilation and venous injuries."

Dr. Preston Miller of Wake Forest University in Winston-Salem, N.C., said that the study "answers some questions and creates a lot of questions as to what we’re doing in respect to PE and VTE prophylaxis in our patients." He asked whether the study accounted for intrinsic or genetic hypercoagulable states in the PE population.

"On TEG, maximal amplitude is mostly reflective of platelet activity; the elevated mA associated with pulmonary embolism may argue that platelet dysfunction is a problem," said Dr. Miller. "Does this argue for a potential role for antiplatelet agents for potential PE and thromboembolism prophylaxis in trauma patients?"

Dr. Cotton acknowledged that further studies are needed to determine whether anticoagulation protocols should be more aggressive. However, at his institution, these patients now get 30 mg of enoxaparin or 5,000 cc of heparin on admission unless they have traumatic brain injury. The investigators said the next step is to develop an algorithm and a guideline based on initiating aspirin along with enoxaparin.

Dr. Steven R. Shackford, who practices in San Diego, offered a likely explanation for the rising incidence of PE in trauma patients: "We have CT now, and instead of getting a pulmonary angiogram, we can now get a CT scan, which is much easier to get," he said.

Dr. Cotton disclosed that although the study received no direct funding, he has done work for Haemonetics Corp., which markets automated blood-processing systems.

CHICAGO – Performing rapid thromboelastography on admission can help trauma surgeons determine which patients are at greatest risk of developing pulmonary embolism, judging by results of a study of more than 8,000 patients.

The incidence of pulmonary embolism (PE), although still below 0.5%, has more than doubled in recent years, according to a recent report using data from the National Trauma Data Bank (Ann. Surg. 2011 Aug. 24 [E-pub ahead of print]).

"Despite this increasing knowledge of risk factors, despite increasing chemoprophylaxis – we’re getting more aggressive with head injuries in starting enoxaparin and heparin, and more aggressive with our spine and solid organ injuries – despite all this, the incidence of PE is increasing," Dr. Bryan A. Cotton said at the annual meeting of the American Association for the Surgery of Trauma.

To learn whether rapid thromboelastography (r-TEG), using a maximum amplitude (mA) greater than 65 mm, could identify patients at risk of developing PE during their hospital stay, Dr. Cotton and his colleagues at the University of Texas Health Science Center in Houston evaluated the use of r-TEG upon admission to the trauma bay for 8,330 total trauma patients over an 18-month period.

"Recent data from multiple institutions have shown an increase in vascular complications following these states if the mA values and certain other portions of TEG values are elevated," Dr. Cotton said. Besides PE and venous thromboembolism (VTE), complications including stroke and postoperative MI have been shown to increase with postoperative and postinjury r-TEG values, he added.

In the Houston study, r-TEG was obtained on 2,070 consecutive trauma patients. Of those, 2.5% went on to develop PE. These patients tended to be older and were more likely to be white and more severely injured than the other patients, and to have only blunt injuries.

"We found the admission mA, which is the highest amplitude of the clot, was associated with risk of developing PE during hospital stay," Dr. Cotton said.

The median time to development of PE was 6 days (duration, 2-31 days), he noted. The investigators also analyzed other factors, and when controlling for male sex, Injury Severity Score, and age, they found that an individual with an mA greater than 65 mm at the time of admission had a 3.5-fold greater odds of developing PE during the hospital stay, Dr. Cotton said. When they raised the threshold to an mA of 72 mm or higher, the risk profile increased sixfold, he said.

"An mA of 65 [mm] or greater is just as good as traditionally noted high-risk factors," Dr. Cotton said. "These include pelvic factures and lower extremity spine and head injuries. When mA is greater than 72 [mm], it exceeds or equals the odds ratio for very-high-risk factors such as prolonged ventilation and venous injuries."

Dr. Preston Miller of Wake Forest University in Winston-Salem, N.C., said that the study "answers some questions and creates a lot of questions as to what we’re doing in respect to PE and VTE prophylaxis in our patients." He asked whether the study accounted for intrinsic or genetic hypercoagulable states in the PE population.

"On TEG, maximal amplitude is mostly reflective of platelet activity; the elevated mA associated with pulmonary embolism may argue that platelet dysfunction is a problem," said Dr. Miller. "Does this argue for a potential role for antiplatelet agents for potential PE and thromboembolism prophylaxis in trauma patients?"

Dr. Cotton acknowledged that further studies are needed to determine whether anticoagulation protocols should be more aggressive. However, at his institution, these patients now get 30 mg of enoxaparin or 5,000 cc of heparin on admission unless they have traumatic brain injury. The investigators said the next step is to develop an algorithm and a guideline based on initiating aspirin along with enoxaparin.

Dr. Steven R. Shackford, who practices in San Diego, offered a likely explanation for the rising incidence of PE in trauma patients: "We have CT now, and instead of getting a pulmonary angiogram, we can now get a CT scan, which is much easier to get," he said.

Dr. Cotton disclosed that although the study received no direct funding, he has done work for Haemonetics Corp., which markets automated blood-processing systems.

CHICAGO – Performing rapid thromboelastography on admission can help trauma surgeons determine which patients are at greatest risk of developing pulmonary embolism, judging by results of a study of more than 8,000 patients.

The incidence of pulmonary embolism (PE), although still below 0.5%, has more than doubled in recent years, according to a recent report using data from the National Trauma Data Bank (Ann. Surg. 2011 Aug. 24 [E-pub ahead of print]).

"Despite this increasing knowledge of risk factors, despite increasing chemoprophylaxis – we’re getting more aggressive with head injuries in starting enoxaparin and heparin, and more aggressive with our spine and solid organ injuries – despite all this, the incidence of PE is increasing," Dr. Bryan A. Cotton said at the annual meeting of the American Association for the Surgery of Trauma.

To learn whether rapid thromboelastography (r-TEG), using a maximum amplitude (mA) greater than 65 mm, could identify patients at risk of developing PE during their hospital stay, Dr. Cotton and his colleagues at the University of Texas Health Science Center in Houston evaluated the use of r-TEG upon admission to the trauma bay for 8,330 total trauma patients over an 18-month period.

"Recent data from multiple institutions have shown an increase in vascular complications following these states if the mA values and certain other portions of TEG values are elevated," Dr. Cotton said. Besides PE and venous thromboembolism (VTE), complications including stroke and postoperative MI have been shown to increase with postoperative and postinjury r-TEG values, he added.

In the Houston study, r-TEG was obtained on 2,070 consecutive trauma patients. Of those, 2.5% went on to develop PE. These patients tended to be older and were more likely to be white and more severely injured than the other patients, and to have only blunt injuries.

"We found the admission mA, which is the highest amplitude of the clot, was associated with risk of developing PE during hospital stay," Dr. Cotton said.

The median time to development of PE was 6 days (duration, 2-31 days), he noted. The investigators also analyzed other factors, and when controlling for male sex, Injury Severity Score, and age, they found that an individual with an mA greater than 65 mm at the time of admission had a 3.5-fold greater odds of developing PE during the hospital stay, Dr. Cotton said. When they raised the threshold to an mA of 72 mm or higher, the risk profile increased sixfold, he said.

"An mA of 65 [mm] or greater is just as good as traditionally noted high-risk factors," Dr. Cotton said. "These include pelvic factures and lower extremity spine and head injuries. When mA is greater than 72 [mm], it exceeds or equals the odds ratio for very-high-risk factors such as prolonged ventilation and venous injuries."

Dr. Preston Miller of Wake Forest University in Winston-Salem, N.C., said that the study "answers some questions and creates a lot of questions as to what we’re doing in respect to PE and VTE prophylaxis in our patients." He asked whether the study accounted for intrinsic or genetic hypercoagulable states in the PE population.

"On TEG, maximal amplitude is mostly reflective of platelet activity; the elevated mA associated with pulmonary embolism may argue that platelet dysfunction is a problem," said Dr. Miller. "Does this argue for a potential role for antiplatelet agents for potential PE and thromboembolism prophylaxis in trauma patients?"

Dr. Cotton acknowledged that further studies are needed to determine whether anticoagulation protocols should be more aggressive. However, at his institution, these patients now get 30 mg of enoxaparin or 5,000 cc of heparin on admission unless they have traumatic brain injury. The investigators said the next step is to develop an algorithm and a guideline based on initiating aspirin along with enoxaparin.

Dr. Steven R. Shackford, who practices in San Diego, offered a likely explanation for the rising incidence of PE in trauma patients: "We have CT now, and instead of getting a pulmonary angiogram, we can now get a CT scan, which is much easier to get," he said.

Dr. Cotton disclosed that although the study received no direct funding, he has done work for Haemonetics Corp., which markets automated blood-processing systems.

PARIS – Patients with severe vitamin D deficiency who underwent vascular surgery faced a significant, 56% increased risk for developing a cardiovascular event during the 30 days following surgery compared with patients who had a sufficient vitamin D level, in a review of 269 patients treated at a single Dutch center.

The study findings did not address whether patients who were vitamin D deficient and then received a vitamin D supplement had a reduced number of postsurgical events, Dr. Koen M. van de Luijtgaarden and his associates from Erasmus University Medical Center in Rotterdam, The Netherlands reported in a poster at the meeting.

The study also documented the frequency of vitamin D deficiency or insufficiency in patients scheduled for vascular surgery. Of the 269 patients included in the review who underwent vascular surgery during 2008-2010 at Erasmus Medical Center, 78 (29%) had a sufficient plasma level of vitamin D at baseline, defined as a 25-hydroxyvitamin D level of greater than 75 nmol/L. In all 38 of the patients (14%) had severe vitamin D deficiency at baseline, defined as 25 nmol/L or less. A total of 76 (28%) had moderate deficiency, defined as more than 25 nmol/L to 50 nmol/L, and 77 (29%) had vitamin D insufficiency, defined as more than 50 nmol/L to 75 nmol/L.

About two-thirds of the surgery patients were men, and the average age of all patients in the review was 66.

The primary endpoint of the study was the rate of cardiovascular events during the first 30 days after surgery, a composite tally that included the rates of cardiovascular deaths, nonfatal myocardial damage, or stroke. The incidence of these events was 38% in the severely deficient patients, 24% in patients with moderate deficiency, 32% in patients with vitamin D insufficiency, and 13% in those with a sufficient level of the vitamin.

In a multivariate analysis that controlled for baseline differences in demographics, medical history, and medications, patients in the severely deficient group had a statistically significant, 56% increased incidence of cardiovascular events, compared with patients with a sufficient vitamin D level. Patients with moderate deficiency or insufficiency both showed trends toward more events compared with the sufficient group, but in neither case was the difference statistically significant.

The findings are consistent with prior reports that vitamin D deficiency links with an increased risk for atherosclerosis and cardiovascular events, said Dr. van de Luijtgaarden, a researcher in the department of vascular surgery at Erasmus, and his associates.

Dr. van de Luijtgaarden said that he and his associates had no disclosures.

PARIS – Patients with severe vitamin D deficiency who underwent vascular surgery faced a significant, 56% increased risk for developing a cardiovascular event during the 30 days following surgery compared with patients who had a sufficient vitamin D level, in a review of 269 patients treated at a single Dutch center.

The study findings did not address whether patients who were vitamin D deficient and then received a vitamin D supplement had a reduced number of postsurgical events, Dr. Koen M. van de Luijtgaarden and his associates from Erasmus University Medical Center in Rotterdam, The Netherlands reported in a poster at the meeting.

The study also documented the frequency of vitamin D deficiency or insufficiency in patients scheduled for vascular surgery. Of the 269 patients included in the review who underwent vascular surgery during 2008-2010 at Erasmus Medical Center, 78 (29%) had a sufficient plasma level of vitamin D at baseline, defined as a 25-hydroxyvitamin D level of greater than 75 nmol/L. In all 38 of the patients (14%) had severe vitamin D deficiency at baseline, defined as 25 nmol/L or less. A total of 76 (28%) had moderate deficiency, defined as more than 25 nmol/L to 50 nmol/L, and 77 (29%) had vitamin D insufficiency, defined as more than 50 nmol/L to 75 nmol/L.

About two-thirds of the surgery patients were men, and the average age of all patients in the review was 66.

The primary endpoint of the study was the rate of cardiovascular events during the first 30 days after surgery, a composite tally that included the rates of cardiovascular deaths, nonfatal myocardial damage, or stroke. The incidence of these events was 38% in the severely deficient patients, 24% in patients with moderate deficiency, 32% in patients with vitamin D insufficiency, and 13% in those with a sufficient level of the vitamin.

In a multivariate analysis that controlled for baseline differences in demographics, medical history, and medications, patients in the severely deficient group had a statistically significant, 56% increased incidence of cardiovascular events, compared with patients with a sufficient vitamin D level. Patients with moderate deficiency or insufficiency both showed trends toward more events compared with the sufficient group, but in neither case was the difference statistically significant.

The findings are consistent with prior reports that vitamin D deficiency links with an increased risk for atherosclerosis and cardiovascular events, said Dr. van de Luijtgaarden, a researcher in the department of vascular surgery at Erasmus, and his associates.

Dr. van de Luijtgaarden said that he and his associates had no disclosures.

PARIS – Patients with severe vitamin D deficiency who underwent vascular surgery faced a significant, 56% increased risk for developing a cardiovascular event during the 30 days following surgery compared with patients who had a sufficient vitamin D level, in a review of 269 patients treated at a single Dutch center.

The study findings did not address whether patients who were vitamin D deficient and then received a vitamin D supplement had a reduced number of postsurgical events, Dr. Koen M. van de Luijtgaarden and his associates from Erasmus University Medical Center in Rotterdam, The Netherlands reported in a poster at the meeting.

The study also documented the frequency of vitamin D deficiency or insufficiency in patients scheduled for vascular surgery. Of the 269 patients included in the review who underwent vascular surgery during 2008-2010 at Erasmus Medical Center, 78 (29%) had a sufficient plasma level of vitamin D at baseline, defined as a 25-hydroxyvitamin D level of greater than 75 nmol/L. In all 38 of the patients (14%) had severe vitamin D deficiency at baseline, defined as 25 nmol/L or less. A total of 76 (28%) had moderate deficiency, defined as more than 25 nmol/L to 50 nmol/L, and 77 (29%) had vitamin D insufficiency, defined as more than 50 nmol/L to 75 nmol/L.

About two-thirds of the surgery patients were men, and the average age of all patients in the review was 66.

The primary endpoint of the study was the rate of cardiovascular events during the first 30 days after surgery, a composite tally that included the rates of cardiovascular deaths, nonfatal myocardial damage, or stroke. The incidence of these events was 38% in the severely deficient patients, 24% in patients with moderate deficiency, 32% in patients with vitamin D insufficiency, and 13% in those with a sufficient level of the vitamin.

In a multivariate analysis that controlled for baseline differences in demographics, medical history, and medications, patients in the severely deficient group had a statistically significant, 56% increased incidence of cardiovascular events, compared with patients with a sufficient vitamin D level. Patients with moderate deficiency or insufficiency both showed trends toward more events compared with the sufficient group, but in neither case was the difference statistically significant.

The findings are consistent with prior reports that vitamin D deficiency links with an increased risk for atherosclerosis and cardiovascular events, said Dr. van de Luijtgaarden, a researcher in the department of vascular surgery at Erasmus, and his associates.

Dr. van de Luijtgaarden said that he and his associates had no disclosures.

A method of administering general anesthesia while monitoring EEG activity to track the patient’s level of consciousness proved to be no better than the standard anesthesia technique at preventing episodes of patient awareness during surgery, according to a study published in the Aug. 18 issue of the New England Journal of Medicine.

"The overall incidence of awareness was lower than anticipated, suggesting that both protocols were likely to have had efficacy, but the finding of fewer cases [with the standard approach than with the EEG method] was contrary to the expected result," said Dr. Michael S. Avidan of the department of anesthesiology at Washington University, St. Louis, and his associates.

"Notwithstanding major advances in our understanding of consciousness and anesthesia, until we clarify fully the mechanisms and measurement of anesthetic-induced unconsciousness and amnesia, some patients are still likely to have this complication," the researchers noted.

Unintended intraoperative awareness (defined as the experience and explicit recall of sensory perceptions during surgery) is estimated to occur in approximately 1% of at-risk patients, and can lead to posttraumatic stress disorder. Approximately 20,000-40,000 U.S. patients each year are estimated to experience such awareness while under general anesthesia.

Some factors that appear to raise the risk of unintended awareness while under general anesthesia are a history of the condition during previous surgery, aortic stenosis, pulmonary hypertension, end-stage lung disease, anticipation of difficult intubation, poor exercise tolerance, impaired cardiac ejection fraction, excess alcohol intake, and the use of benzodiazepines, opiates, or anticonvulsants.

The current standard method for monitoring intraoperative patient awareness doesn’t measure consciousness itself, but instead ensures that "enough" anesthetic is used by tracking the end-tidal anesthetic-agent concentration (ETAC). Maintaining this at 0.7 MAC (minimum alveolar concentration) or higher is thought to decrease the incidence of awareness during surgery.

An alternative method is the bispectral index (BIS), which uses a single EEG signal from a sensor on the patient’s forehead to calculate brain activity and produces a numerical readout on a scale from 0 (indicating the suppression of all brain activity) to 100 (indicating a fully awake state). Maintaining a target range of 40-60 on this scale is thought to both prevent awareness and allow reductions in the dose of anesthetic.

Two previous clinical trials comparing the two techniques have yielded conflicting results.

Dr. Avidan and his colleagues conducted the BAG-RECALL (BIS or Anesthetic Gas to Reduce Explicit Recall) clinical trial to determine whether the BIS method is superior to standard ETAC in at-risk surgical patients.

They randomly assigned 6,041 adults undergoing elective surgery during a 2-year period at three medical centers in the United States and Canada to one or the other technique. In the BIS group, an alarm sounded when the BIS value exceeded 60 or fell below 40. In the ETAC group, an alarm sounded if the ETAC fell below 0.7 or exceeded 1.3 MAC.

In both study groups, a sign was attached to the anesthesia machines reminding clinicians to check these values and consider whether the patient might be aware. In addition, these values were recorded electronically at 1-minute intervals; manual records were kept of anesthesia; and photographs of trends on the monitors were taken and stored digitally.

There were no important differences between the two groups in doses of sedative, hypnotic, opioid, analgesic, or neuromuscular-blocking drugs given, nor in the amount of anesthetic given; the rate of adverse postoperative outcomes including mortality; the median length of stay in intensive care; or the median length of hospital stay.

Patients’ intraoperative awareness was assessed via a questionnaire within 72 hours after surgery and at 30 days after extubation. A total of 49 patients reported some degree of awareness at some time when they were undergoing surgery, Dr. Avidan and his associates said (N. Engl. J. Med. 2011;365:591-600).

All patients who reported that they had memories of the period between "going to sleep" and "waking up" from anesthesia were further evaluated in more detail and were offered referral to a psychologist for counseling.

Contrary to expectations, there were fewer cases of definite intraoperative awareness in the ETAC group (0.07%) than in the BIS group (0.24%). Similarly, there were fewer cases of possible or definite intraoperative awareness in the ETAC group (0.28%) than in the BIS group (0.66%).

Thus, BIS was not superior in preventing intraoperative awareness.

This study was supported by the Foundation for Anesthesia Education and Research, the American Society of Anesthesiologists, the Winnipeg Regional Health Authority, and the departments of anesthesia at the University of Manitoba, Washington University, and the University of Chicago. The researchers reported no financial conflicts of interest.

A method of administering general anesthesia while monitoring EEG activity to track the patient’s level of consciousness proved to be no better than the standard anesthesia technique at preventing episodes of patient awareness during surgery, according to a study published in the Aug. 18 issue of the New England Journal of Medicine.

"The overall incidence of awareness was lower than anticipated, suggesting that both protocols were likely to have had efficacy, but the finding of fewer cases [with the standard approach than with the EEG method] was contrary to the expected result," said Dr. Michael S. Avidan of the department of anesthesiology at Washington University, St. Louis, and his associates.

"Notwithstanding major advances in our understanding of consciousness and anesthesia, until we clarify fully the mechanisms and measurement of anesthetic-induced unconsciousness and amnesia, some patients are still likely to have this complication," the researchers noted.

Unintended intraoperative awareness (defined as the experience and explicit recall of sensory perceptions during surgery) is estimated to occur in approximately 1% of at-risk patients, and can lead to posttraumatic stress disorder. Approximately 20,000-40,000 U.S. patients each year are estimated to experience such awareness while under general anesthesia.

Some factors that appear to raise the risk of unintended awareness while under general anesthesia are a history of the condition during previous surgery, aortic stenosis, pulmonary hypertension, end-stage lung disease, anticipation of difficult intubation, poor exercise tolerance, impaired cardiac ejection fraction, excess alcohol intake, and the use of benzodiazepines, opiates, or anticonvulsants.

The current standard method for monitoring intraoperative patient awareness doesn’t measure consciousness itself, but instead ensures that "enough" anesthetic is used by tracking the end-tidal anesthetic-agent concentration (ETAC). Maintaining this at 0.7 MAC (minimum alveolar concentration) or higher is thought to decrease the incidence of awareness during surgery.

An alternative method is the bispectral index (BIS), which uses a single EEG signal from a sensor on the patient’s forehead to calculate brain activity and produces a numerical readout on a scale from 0 (indicating the suppression of all brain activity) to 100 (indicating a fully awake state). Maintaining a target range of 40-60 on this scale is thought to both prevent awareness and allow reductions in the dose of anesthetic.

Two previous clinical trials comparing the two techniques have yielded conflicting results.

Dr. Avidan and his colleagues conducted the BAG-RECALL (BIS or Anesthetic Gas to Reduce Explicit Recall) clinical trial to determine whether the BIS method is superior to standard ETAC in at-risk surgical patients.

They randomly assigned 6,041 adults undergoing elective surgery during a 2-year period at three medical centers in the United States and Canada to one or the other technique. In the BIS group, an alarm sounded when the BIS value exceeded 60 or fell below 40. In the ETAC group, an alarm sounded if the ETAC fell below 0.7 or exceeded 1.3 MAC.

In both study groups, a sign was attached to the anesthesia machines reminding clinicians to check these values and consider whether the patient might be aware. In addition, these values were recorded electronically at 1-minute intervals; manual records were kept of anesthesia; and photographs of trends on the monitors were taken and stored digitally.

There were no important differences between the two groups in doses of sedative, hypnotic, opioid, analgesic, or neuromuscular-blocking drugs given, nor in the amount of anesthetic given; the rate of adverse postoperative outcomes including mortality; the median length of stay in intensive care; or the median length of hospital stay.

Patients’ intraoperative awareness was assessed via a questionnaire within 72 hours after surgery and at 30 days after extubation. A total of 49 patients reported some degree of awareness at some time when they were undergoing surgery, Dr. Avidan and his associates said (N. Engl. J. Med. 2011;365:591-600).

All patients who reported that they had memories of the period between "going to sleep" and "waking up" from anesthesia were further evaluated in more detail and were offered referral to a psychologist for counseling.

Contrary to expectations, there were fewer cases of definite intraoperative awareness in the ETAC group (0.07%) than in the BIS group (0.24%). Similarly, there were fewer cases of possible or definite intraoperative awareness in the ETAC group (0.28%) than in the BIS group (0.66%).

Thus, BIS was not superior in preventing intraoperative awareness.

This study was supported by the Foundation for Anesthesia Education and Research, the American Society of Anesthesiologists, the Winnipeg Regional Health Authority, and the departments of anesthesia at the University of Manitoba, Washington University, and the University of Chicago. The researchers reported no financial conflicts of interest.

A method of administering general anesthesia while monitoring EEG activity to track the patient’s level of consciousness proved to be no better than the standard anesthesia technique at preventing episodes of patient awareness during surgery, according to a study published in the Aug. 18 issue of the New England Journal of Medicine.

"The overall incidence of awareness was lower than anticipated, suggesting that both protocols were likely to have had efficacy, but the finding of fewer cases [with the standard approach than with the EEG method] was contrary to the expected result," said Dr. Michael S. Avidan of the department of anesthesiology at Washington University, St. Louis, and his associates.

"Notwithstanding major advances in our understanding of consciousness and anesthesia, until we clarify fully the mechanisms and measurement of anesthetic-induced unconsciousness and amnesia, some patients are still likely to have this complication," the researchers noted.

Unintended intraoperative awareness (defined as the experience and explicit recall of sensory perceptions during surgery) is estimated to occur in approximately 1% of at-risk patients, and can lead to posttraumatic stress disorder. Approximately 20,000-40,000 U.S. patients each year are estimated to experience such awareness while under general anesthesia.

Some factors that appear to raise the risk of unintended awareness while under general anesthesia are a history of the condition during previous surgery, aortic stenosis, pulmonary hypertension, end-stage lung disease, anticipation of difficult intubation, poor exercise tolerance, impaired cardiac ejection fraction, excess alcohol intake, and the use of benzodiazepines, opiates, or anticonvulsants.

The current standard method for monitoring intraoperative patient awareness doesn’t measure consciousness itself, but instead ensures that "enough" anesthetic is used by tracking the end-tidal anesthetic-agent concentration (ETAC). Maintaining this at 0.7 MAC (minimum alveolar concentration) or higher is thought to decrease the incidence of awareness during surgery.

An alternative method is the bispectral index (BIS), which uses a single EEG signal from a sensor on the patient’s forehead to calculate brain activity and produces a numerical readout on a scale from 0 (indicating the suppression of all brain activity) to 100 (indicating a fully awake state). Maintaining a target range of 40-60 on this scale is thought to both prevent awareness and allow reductions in the dose of anesthetic.

Two previous clinical trials comparing the two techniques have yielded conflicting results.

Dr. Avidan and his colleagues conducted the BAG-RECALL (BIS or Anesthetic Gas to Reduce Explicit Recall) clinical trial to determine whether the BIS method is superior to standard ETAC in at-risk surgical patients.

They randomly assigned 6,041 adults undergoing elective surgery during a 2-year period at three medical centers in the United States and Canada to one or the other technique. In the BIS group, an alarm sounded when the BIS value exceeded 60 or fell below 40. In the ETAC group, an alarm sounded if the ETAC fell below 0.7 or exceeded 1.3 MAC.

In both study groups, a sign was attached to the anesthesia machines reminding clinicians to check these values and consider whether the patient might be aware. In addition, these values were recorded electronically at 1-minute intervals; manual records were kept of anesthesia; and photographs of trends on the monitors were taken and stored digitally.

There were no important differences between the two groups in doses of sedative, hypnotic, opioid, analgesic, or neuromuscular-blocking drugs given, nor in the amount of anesthetic given; the rate of adverse postoperative outcomes including mortality; the median length of stay in intensive care; or the median length of hospital stay.

Patients’ intraoperative awareness was assessed via a questionnaire within 72 hours after surgery and at 30 days after extubation. A total of 49 patients reported some degree of awareness at some time when they were undergoing surgery, Dr. Avidan and his associates said (N. Engl. J. Med. 2011;365:591-600).

All patients who reported that they had memories of the period between "going to sleep" and "waking up" from anesthesia were further evaluated in more detail and were offered referral to a psychologist for counseling.

Contrary to expectations, there were fewer cases of definite intraoperative awareness in the ETAC group (0.07%) than in the BIS group (0.24%). Similarly, there were fewer cases of possible or definite intraoperative awareness in the ETAC group (0.28%) than in the BIS group (0.66%).

Thus, BIS was not superior in preventing intraoperative awareness.

This study was supported by the Foundation for Anesthesia Education and Research, the American Society of Anesthesiologists, the Winnipeg Regional Health Authority, and the departments of anesthesia at the University of Manitoba, Washington University, and the University of Chicago. The researchers reported no financial conflicts of interest.

KANSAS CITY, MO. – Seventeen percent of American children and adolescents are obese, and an increasing number of them are landing in operating rooms for related issues. They bring to the table particular perioperative concerns.

Dr. Moises Auron of the Cleveland Clinic offered an example during a talk on pediatric perioperative management at the Pediatric Hospital Medicine 2011 meeting: A 15-year-old African American with a body mass index of 60 kg/m², fasting blood glucose of 115 mg/dL, and glycated hemoglobin of 6.4%, and who smokes, requires pinning of his hip for slipped capital femoral epiphysis.

For this high-risk patient, he said, cardiovascular concerns top the list, because obese children and adolescents are predisposed to hypertension at roughly a threefold higher risk than nonobese children. As a result, they can develop left ventricular hypertrophy that can produce a hypertrophic cardiomyopathy–like scenario, as well as diastolic dysfunction that also can predispose them to develop heart failure.

Childhood obesity is typically defined as a BMI at or above the 95th percentile for age and sex, while morbid obesity, as in the above patient, is a BMI that exceeds the 99th percentile.

Three times as many U.S. youth are obese now as were just one generation ago, the most recent data from the Centers for Disease Control and Prevention suggest. In addition, one in seven low-income, preschool-aged children is obese.

"Unfortunately, we are seeing more and more and more of these cases," said Dr. Auron, a pediatric hospitalist with the Center for Pediatric Hospital Medicine at the Cleveland Clinic.

Obese patients may require surgery not only for a variety of common ailments such as tonsillitis, but also for obesity-related conditions such as slipped capital femoral epiphysis, Blount’s disease, cholelithiasis, and polycystic ovary syndrome. In addition, they present with comorbid conditions such as insulin resistance, hypertension, and idiopathic intracranial hypertension.

What to Look for in Obese Patients

In the examination of these patients, Dr. Auron suggests that the history include any symptoms of sleep apnea or hypoventilation, such as falling asleep while watching television or when talking with friends, and poor tolerance to exercise, including breathlessness and asthma, because these may in fact represent symptoms of left ventricular dysfunction.

Documentation of recent weight loss or gain, as well as a careful history of current medications – especially herbs or special mixtures taken to lose weight – is paramount. Weight loss may be associated with malnutrition, while the use of common herbs can interfere with anesthesia or hemostasis and even be associated with tachycardia, hypertension, or dysrhythmias.

"Garlic and ginger are very good antiplatelet agents," he said. "It’s like taking baby aspirin, but it’s not good if you’re having surgery. You can bleed to death.

"Medications that contain ephedra can trigger a severe sympathetic response, including hypertensive crises and tachyarrhythmias."

Other perioperative considerations to be wary of in the morbidly obese pediatric patient are diabetes/insulin resistance; gastroesophageal reflux; and nonalcoholic fatty liver disease (NAFLD), including its progressive form, nonalcoholic steatohepatitis (NASH).

"When they develop NASH, it can evolve to cirrhosis, horribly," Dr. Auron said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association. "It’s even worse than alcoholic cirrhosis or viral hepatitis cirrhosis. I’m not sure why this is, but it causes substantial morbidity in the obese population who develops it."

The prevalence of NAFLD and NASH varies by setting. Among 41 morbidly obese adolescents aged 13-19 years undergoing gastric bypass surgery, 83% had NAFLD and 20% had NASH. Mean fasting glucose was significantly higher in those with NASH, although the prevalence of the metabolic syndrome was not (Gastroenterol. Hepatol. 2006;4:226-32).

A second study, however, recently reported that fatty liver disease, independent of visceral fat and intramyocellular lipid content, plays a central role in the pathogenesis of insulin resistance in obese adolescents (Diabetes Care 2010;33:1817-22).

Dr. Auron said he recommends echocardiography for hypertensive patients, although he noted that there is not a lot of evidence, even in the adult literature, to support an echocardiogram for every patient. The one exception is patients with cardiomegaly on x-ray; echocardiography is recommended for this patient group (Circulation 2009;120:86-95).

Preoperative fasting should follow the same rules as for nonobese patients, albeit perhaps a bit more fasting would not lead obese patients astray, he said, tongue in cheek.

Dr. Auron reported no relevant financial relationships.

KANSAS CITY, MO. – Seventeen percent of American children and adolescents are obese, and an increasing number of them are landing in operating rooms for related issues. They bring to the table particular perioperative concerns.

Dr. Moises Auron of the Cleveland Clinic offered an example during a talk on pediatric perioperative management at the Pediatric Hospital Medicine 2011 meeting: A 15-year-old African American with a body mass index of 60 kg/m², fasting blood glucose of 115 mg/dL, and glycated hemoglobin of 6.4%, and who smokes, requires pinning of his hip for slipped capital femoral epiphysis.

For this high-risk patient, he said, cardiovascular concerns top the list, because obese children and adolescents are predisposed to hypertension at roughly a threefold higher risk than nonobese children. As a result, they can develop left ventricular hypertrophy that can produce a hypertrophic cardiomyopathy–like scenario, as well as diastolic dysfunction that also can predispose them to develop heart failure.

Childhood obesity is typically defined as a BMI at or above the 95th percentile for age and sex, while morbid obesity, as in the above patient, is a BMI that exceeds the 99th percentile.

Three times as many U.S. youth are obese now as were just one generation ago, the most recent data from the Centers for Disease Control and Prevention suggest. In addition, one in seven low-income, preschool-aged children is obese.

"Unfortunately, we are seeing more and more and more of these cases," said Dr. Auron, a pediatric hospitalist with the Center for Pediatric Hospital Medicine at the Cleveland Clinic.

Obese patients may require surgery not only for a variety of common ailments such as tonsillitis, but also for obesity-related conditions such as slipped capital femoral epiphysis, Blount’s disease, cholelithiasis, and polycystic ovary syndrome. In addition, they present with comorbid conditions such as insulin resistance, hypertension, and idiopathic intracranial hypertension.

What to Look for in Obese Patients

In the examination of these patients, Dr. Auron suggests that the history include any symptoms of sleep apnea or hypoventilation, such as falling asleep while watching television or when talking with friends, and poor tolerance to exercise, including breathlessness and asthma, because these may in fact represent symptoms of left ventricular dysfunction.

Documentation of recent weight loss or gain, as well as a careful history of current medications – especially herbs or special mixtures taken to lose weight – is paramount. Weight loss may be associated with malnutrition, while the use of common herbs can interfere with anesthesia or hemostasis and even be associated with tachycardia, hypertension, or dysrhythmias.

"Garlic and ginger are very good antiplatelet agents," he said. "It’s like taking baby aspirin, but it’s not good if you’re having surgery. You can bleed to death.

"Medications that contain ephedra can trigger a severe sympathetic response, including hypertensive crises and tachyarrhythmias."

Other perioperative considerations to be wary of in the morbidly obese pediatric patient are diabetes/insulin resistance; gastroesophageal reflux; and nonalcoholic fatty liver disease (NAFLD), including its progressive form, nonalcoholic steatohepatitis (NASH).

"When they develop NASH, it can evolve to cirrhosis, horribly," Dr. Auron said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association. "It’s even worse than alcoholic cirrhosis or viral hepatitis cirrhosis. I’m not sure why this is, but it causes substantial morbidity in the obese population who develops it."

The prevalence of NAFLD and NASH varies by setting. Among 41 morbidly obese adolescents aged 13-19 years undergoing gastric bypass surgery, 83% had NAFLD and 20% had NASH. Mean fasting glucose was significantly higher in those with NASH, although the prevalence of the metabolic syndrome was not (Gastroenterol. Hepatol. 2006;4:226-32).

A second study, however, recently reported that fatty liver disease, independent of visceral fat and intramyocellular lipid content, plays a central role in the pathogenesis of insulin resistance in obese adolescents (Diabetes Care 2010;33:1817-22).

Dr. Auron said he recommends echocardiography for hypertensive patients, although he noted that there is not a lot of evidence, even in the adult literature, to support an echocardiogram for every patient. The one exception is patients with cardiomegaly on x-ray; echocardiography is recommended for this patient group (Circulation 2009;120:86-95).

Preoperative fasting should follow the same rules as for nonobese patients, albeit perhaps a bit more fasting would not lead obese patients astray, he said, tongue in cheek.

Dr. Auron reported no relevant financial relationships.

KANSAS CITY, MO. – Seventeen percent of American children and adolescents are obese, and an increasing number of them are landing in operating rooms for related issues. They bring to the table particular perioperative concerns.

Dr. Moises Auron of the Cleveland Clinic offered an example during a talk on pediatric perioperative management at the Pediatric Hospital Medicine 2011 meeting: A 15-year-old African American with a body mass index of 60 kg/m², fasting blood glucose of 115 mg/dL, and glycated hemoglobin of 6.4%, and who smokes, requires pinning of his hip for slipped capital femoral epiphysis.

For this high-risk patient, he said, cardiovascular concerns top the list, because obese children and adolescents are predisposed to hypertension at roughly a threefold higher risk than nonobese children. As a result, they can develop left ventricular hypertrophy that can produce a hypertrophic cardiomyopathy–like scenario, as well as diastolic dysfunction that also can predispose them to develop heart failure.

Childhood obesity is typically defined as a BMI at or above the 95th percentile for age and sex, while morbid obesity, as in the above patient, is a BMI that exceeds the 99th percentile.

Three times as many U.S. youth are obese now as were just one generation ago, the most recent data from the Centers for Disease Control and Prevention suggest. In addition, one in seven low-income, preschool-aged children is obese.

"Unfortunately, we are seeing more and more and more of these cases," said Dr. Auron, a pediatric hospitalist with the Center for Pediatric Hospital Medicine at the Cleveland Clinic.

Obese patients may require surgery not only for a variety of common ailments such as tonsillitis, but also for obesity-related conditions such as slipped capital femoral epiphysis, Blount’s disease, cholelithiasis, and polycystic ovary syndrome. In addition, they present with comorbid conditions such as insulin resistance, hypertension, and idiopathic intracranial hypertension.

What to Look for in Obese Patients

In the examination of these patients, Dr. Auron suggests that the history include any symptoms of sleep apnea or hypoventilation, such as falling asleep while watching television or when talking with friends, and poor tolerance to exercise, including breathlessness and asthma, because these may in fact represent symptoms of left ventricular dysfunction.

Documentation of recent weight loss or gain, as well as a careful history of current medications – especially herbs or special mixtures taken to lose weight – is paramount. Weight loss may be associated with malnutrition, while the use of common herbs can interfere with anesthesia or hemostasis and even be associated with tachycardia, hypertension, or dysrhythmias.

"Garlic and ginger are very good antiplatelet agents," he said. "It’s like taking baby aspirin, but it’s not good if you’re having surgery. You can bleed to death.

"Medications that contain ephedra can trigger a severe sympathetic response, including hypertensive crises and tachyarrhythmias."

Other perioperative considerations to be wary of in the morbidly obese pediatric patient are diabetes/insulin resistance; gastroesophageal reflux; and nonalcoholic fatty liver disease (NAFLD), including its progressive form, nonalcoholic steatohepatitis (NASH).

"When they develop NASH, it can evolve to cirrhosis, horribly," Dr. Auron said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association. "It’s even worse than alcoholic cirrhosis or viral hepatitis cirrhosis. I’m not sure why this is, but it causes substantial morbidity in the obese population who develops it."

The prevalence of NAFLD and NASH varies by setting. Among 41 morbidly obese adolescents aged 13-19 years undergoing gastric bypass surgery, 83% had NAFLD and 20% had NASH. Mean fasting glucose was significantly higher in those with NASH, although the prevalence of the metabolic syndrome was not (Gastroenterol. Hepatol. 2006;4:226-32).

A second study, however, recently reported that fatty liver disease, independent of visceral fat and intramyocellular lipid content, plays a central role in the pathogenesis of insulin resistance in obese adolescents (Diabetes Care 2010;33:1817-22).

Dr. Auron said he recommends echocardiography for hypertensive patients, although he noted that there is not a lot of evidence, even in the adult literature, to support an echocardiogram for every patient. The one exception is patients with cardiomegaly on x-ray; echocardiography is recommended for this patient group (Circulation 2009;120:86-95).

Preoperative fasting should follow the same rules as for nonobese patients, albeit perhaps a bit more fasting would not lead obese patients astray, he said, tongue in cheek.

Dr. Auron reported no relevant financial relationships.

COLORADO SPRINGS – Physicians at Emory University Hospital now have a firmer grip on what they’re dealing with in reducing 30-day readmissions.

The knowledge that there are three major risk factors – preoperative failure to thrive, an initial length of stay greater than 10 days, and Hispanic ethnicity – for readmission following pediatric congenital heart disease surgery is a tool for improvement, said Dr. Brian E. Kogon of Emory University, Atlanta.

"These data are obviously our data and are very specific to our hospital, our location, and our patient population. I would think that it’s going to be very different throughout the country based on whether you’re at an academic center or private center, urban versus rural setting, and even in adult cardiac, general thoracic, and pediatric practices," Dr. Kogon said in presenting the study findings at the annual meeting of the Western Thoracic Surgical Association.

The important thing is for physicians and surgeons to analyze their own hospital’s readmission experience, identify the risk factors, and then address the potentially modifiable ones in an effort to drive that readmission rate down, added Dr. Kogon, director of the congenital cardiac surgery fellowship program at Emory.

Studying Readmissions Following Pediatric Surgery

Readmissions within 30 days are increasingly viewed by third-party payers as preventable complications warranting stiff payment penalties. The focus thus far has been on the adult world, but at some point pediatric care will come under scrutiny as well. This realization led Dr. Kogon and his coworkers to analyze their institutional experience via a retrospective cohort study.

During 2002-2009, the annual 30-day readmission rates following pediatric surgery for congenital heart disease were 5.9%-10.4%, with a median of 8.7%. Those rates are relatively low; other centers typically report readmission rates of 10%-20%, he noted.

In 2009, 685 patients were discharged after pediatric congenital heart disease surgery; 70 of them had 74 readmissions. Among the key findings: only 15% of readmissions were for cardiac reasons. Indeed, the top three reasons for readmission were pleural or pericardial effusions, accounting for 26% of all readmissions; gastrointestinal problems, 24%; and infection, 19%.

Readmissions were costly. A total of 69% of patients were readmitted to a ward, 31% to the ICU. Upon readmission these patients spent a total of 653 additional days – almost 22 months – in the hospital.

The investigators scrutinized numerous potential demographic, preoperative, operative, and postoperative risk factors for readmission. Only three proved significant in a multivariate analysis: an initial length of stay greater than 10 days was associated with a 4.4-fold increased risk of readmission; a preoperative diagnosis of failure to thrive was associated with a 2.7-fold risk; and Hispanic ethnicity was associated with a 1.87-fold increased risk.

These readmissions occurred despite an intense discharge process and close follow-up. All families at the pediatric heart surgery unit attend a discharge class and a CPR training class. A pharmacist is on hand at the discharge class to review medications. Shunt recipients and newborns receive additional education. All case-management issues, such as formula supplies and home health equipment, are resolved before discharge. Patients meet with a cardiothoracic surgeon during their first week out of hospital, a cardiologist the second week, and thereafter with their primary care provider.

The median time to the first scheduled outpatient appointment was 4.5 days postdischarge. The median time to readmission was 8 days. Thirty-one percent of patients were readmitted prior to their first clinic appointment, 10% directly from the clinic, and 50% after their first clinic visit. The rest were readmitted after being no-shows for their clinic visit.

Dr. Kogon said he suspects that Hispanics were at increased risk for readmission because of educational and language barriers. Although a Spanish-language interpreter is present at the discharge class as needed, Dr. Kogon and his colleagues have observed that many Hispanic families nonetheless return unclear about medication and feeding regimens.

"I think there’s still a gap in our education of those patients," he said.

Discussant Dr. David R. Clarke said it might be argued that if a hospital doesn’t have a certain number of readmissions, then patients are being kept in the hospital too long.

"On a practical level, how much do we spend during the initial admission to ensure no readmissions? Do we automatically keep patients identified as high risk, such as Hispanics, 2, 3, or 4 extra days to minimize their readmission rate? And even if we do that and other things, is it really possible to prevent readmissions?" wondered Dr. Clarke of Children’s Hospital Colorado, Denver.

Dr. Kogon replied that this is the key question his colleagues raised when he shared the study findings. The group has decided to modify the discharge process for their high-risk patients, keeping them in the hospital a day or so longer while continuing to collect data in order to see if this pays off in fewer readmissions.

Dr. Kogon declared having no financial conflicts.

COLORADO SPRINGS – Physicians at Emory University Hospital now have a firmer grip on what they’re dealing with in reducing 30-day readmissions.

The knowledge that there are three major risk factors – preoperative failure to thrive, an initial length of stay greater than 10 days, and Hispanic ethnicity – for readmission following pediatric congenital heart disease surgery is a tool for improvement, said Dr. Brian E. Kogon of Emory University, Atlanta.

"These data are obviously our data and are very specific to our hospital, our location, and our patient population. I would think that it’s going to be very different throughout the country based on whether you’re at an academic center or private center, urban versus rural setting, and even in adult cardiac, general thoracic, and pediatric practices," Dr. Kogon said in presenting the study findings at the annual meeting of the Western Thoracic Surgical Association.

The important thing is for physicians and surgeons to analyze their own hospital’s readmission experience, identify the risk factors, and then address the potentially modifiable ones in an effort to drive that readmission rate down, added Dr. Kogon, director of the congenital cardiac surgery fellowship program at Emory.

Studying Readmissions Following Pediatric Surgery

Readmissions within 30 days are increasingly viewed by third-party payers as preventable complications warranting stiff payment penalties. The focus thus far has been on the adult world, but at some point pediatric care will come under scrutiny as well. This realization led Dr. Kogon and his coworkers to analyze their institutional experience via a retrospective cohort study.

During 2002-2009, the annual 30-day readmission rates following pediatric surgery for congenital heart disease were 5.9%-10.4%, with a median of 8.7%. Those rates are relatively low; other centers typically report readmission rates of 10%-20%, he noted.

In 2009, 685 patients were discharged after pediatric congenital heart disease surgery; 70 of them had 74 readmissions. Among the key findings: only 15% of readmissions were for cardiac reasons. Indeed, the top three reasons for readmission were pleural or pericardial effusions, accounting for 26% of all readmissions; gastrointestinal problems, 24%; and infection, 19%.

Readmissions were costly. A total of 69% of patients were readmitted to a ward, 31% to the ICU. Upon readmission these patients spent a total of 653 additional days – almost 22 months – in the hospital.

The investigators scrutinized numerous potential demographic, preoperative, operative, and postoperative risk factors for readmission. Only three proved significant in a multivariate analysis: an initial length of stay greater than 10 days was associated with a 4.4-fold increased risk of readmission; a preoperative diagnosis of failure to thrive was associated with a 2.7-fold risk; and Hispanic ethnicity was associated with a 1.87-fold increased risk.

These readmissions occurred despite an intense discharge process and close follow-up. All families at the pediatric heart surgery unit attend a discharge class and a CPR training class. A pharmacist is on hand at the discharge class to review medications. Shunt recipients and newborns receive additional education. All case-management issues, such as formula supplies and home health equipment, are resolved before discharge. Patients meet with a cardiothoracic surgeon during their first week out of hospital, a cardiologist the second week, and thereafter with their primary care provider.

The median time to the first scheduled outpatient appointment was 4.5 days postdischarge. The median time to readmission was 8 days. Thirty-one percent of patients were readmitted prior to their first clinic appointment, 10% directly from the clinic, and 50% after their first clinic visit. The rest were readmitted after being no-shows for their clinic visit.

Dr. Kogon said he suspects that Hispanics were at increased risk for readmission because of educational and language barriers. Although a Spanish-language interpreter is present at the discharge class as needed, Dr. Kogon and his colleagues have observed that many Hispanic families nonetheless return unclear about medication and feeding regimens.

"I think there’s still a gap in our education of those patients," he said.

Discussant Dr. David R. Clarke said it might be argued that if a hospital doesn’t have a certain number of readmissions, then patients are being kept in the hospital too long.

"On a practical level, how much do we spend during the initial admission to ensure no readmissions? Do we automatically keep patients identified as high risk, such as Hispanics, 2, 3, or 4 extra days to minimize their readmission rate? And even if we do that and other things, is it really possible to prevent readmissions?" wondered Dr. Clarke of Children’s Hospital Colorado, Denver.

Dr. Kogon replied that this is the key question his colleagues raised when he shared the study findings. The group has decided to modify the discharge process for their high-risk patients, keeping them in the hospital a day or so longer while continuing to collect data in order to see if this pays off in fewer readmissions.

Dr. Kogon declared having no financial conflicts.

COLORADO SPRINGS – Physicians at Emory University Hospital now have a firmer grip on what they’re dealing with in reducing 30-day readmissions.

The knowledge that there are three major risk factors – preoperative failure to thrive, an initial length of stay greater than 10 days, and Hispanic ethnicity – for readmission following pediatric congenital heart disease surgery is a tool for improvement, said Dr. Brian E. Kogon of Emory University, Atlanta.

"These data are obviously our data and are very specific to our hospital, our location, and our patient population. I would think that it’s going to be very different throughout the country based on whether you’re at an academic center or private center, urban versus rural setting, and even in adult cardiac, general thoracic, and pediatric practices," Dr. Kogon said in presenting the study findings at the annual meeting of the Western Thoracic Surgical Association.

The important thing is for physicians and surgeons to analyze their own hospital’s readmission experience, identify the risk factors, and then address the potentially modifiable ones in an effort to drive that readmission rate down, added Dr. Kogon, director of the congenital cardiac surgery fellowship program at Emory.

Studying Readmissions Following Pediatric Surgery

Readmissions within 30 days are increasingly viewed by third-party payers as preventable complications warranting stiff payment penalties. The focus thus far has been on the adult world, but at some point pediatric care will come under scrutiny as well. This realization led Dr. Kogon and his coworkers to analyze their institutional experience via a retrospective cohort study.

During 2002-2009, the annual 30-day readmission rates following pediatric surgery for congenital heart disease were 5.9%-10.4%, with a median of 8.7%. Those rates are relatively low; other centers typically report readmission rates of 10%-20%, he noted.

In 2009, 685 patients were discharged after pediatric congenital heart disease surgery; 70 of them had 74 readmissions. Among the key findings: only 15% of readmissions were for cardiac reasons. Indeed, the top three reasons for readmission were pleural or pericardial effusions, accounting for 26% of all readmissions; gastrointestinal problems, 24%; and infection, 19%.

Readmissions were costly. A total of 69% of patients were readmitted to a ward, 31% to the ICU. Upon readmission these patients spent a total of 653 additional days – almost 22 months – in the hospital.

The investigators scrutinized numerous potential demographic, preoperative, operative, and postoperative risk factors for readmission. Only three proved significant in a multivariate analysis: an initial length of stay greater than 10 days was associated with a 4.4-fold increased risk of readmission; a preoperative diagnosis of failure to thrive was associated with a 2.7-fold risk; and Hispanic ethnicity was associated with a 1.87-fold increased risk.

These readmissions occurred despite an intense discharge process and close follow-up. All families at the pediatric heart surgery unit attend a discharge class and a CPR training class. A pharmacist is on hand at the discharge class to review medications. Shunt recipients and newborns receive additional education. All case-management issues, such as formula supplies and home health equipment, are resolved before discharge. Patients meet with a cardiothoracic surgeon during their first week out of hospital, a cardiologist the second week, and thereafter with their primary care provider.

The median time to the first scheduled outpatient appointment was 4.5 days postdischarge. The median time to readmission was 8 days. Thirty-one percent of patients were readmitted prior to their first clinic appointment, 10% directly from the clinic, and 50% after their first clinic visit. The rest were readmitted after being no-shows for their clinic visit.

Dr. Kogon said he suspects that Hispanics were at increased risk for readmission because of educational and language barriers. Although a Spanish-language interpreter is present at the discharge class as needed, Dr. Kogon and his colleagues have observed that many Hispanic families nonetheless return unclear about medication and feeding regimens.

"I think there’s still a gap in our education of those patients," he said.

Discussant Dr. David R. Clarke said it might be argued that if a hospital doesn’t have a certain number of readmissions, then patients are being kept in the hospital too long.

"On a practical level, how much do we spend during the initial admission to ensure no readmissions? Do we automatically keep patients identified as high risk, such as Hispanics, 2, 3, or 4 extra days to minimize their readmission rate? And even if we do that and other things, is it really possible to prevent readmissions?" wondered Dr. Clarke of Children’s Hospital Colorado, Denver.

Dr. Kogon replied that this is the key question his colleagues raised when he shared the study findings. The group has decided to modify the discharge process for their high-risk patients, keeping them in the hospital a day or so longer while continuing to collect data in order to see if this pays off in fewer readmissions.

Dr. Kogon declared having no financial conflicts.

Blood loss from diagnostic blood testing during hospitalization is substantial and has been linked to anemia in patients with acute myocardial infarction, according to a study published online Aug. 8 in the Archives of Internal Medicine.

In a study of 17,676 MI patients at 57 U.S. hospitals, 1 in 5 patients developed moderate to severe hospital-acquired anemia, and they had a mean estimated phlebotomy volume of 173.8 mL – the equivalent of half a unit of whole blood. Twelve percent of the study subjects lost more than 300 mL to blood draws during the course of their hospitalization, said Dr. Adam C. Salisbury of Saint Luke’s Mid America Heart and Vascular Institute, Kansas City, Mo., and his associates.

Photo (c) Pearl Jackson/iStock.com

"Our findings are likely generalizable to other populations of seriously ill medical patients," they noted.

If further research establishes that minimizing blood loss from phlebotomy prevents anemia and improves patient outcomes, there would be broad implications for all hospitalized patients. Strategies to minimize blood loss, such as using pediatric instead of adult blood tubes or filling standard 4-mL adult tubes with only 1-2 mL of blood, would be widely adopted, Dr. Salisbury and his colleagues added.

They explored the relationship between diagnostic blood testing and the risk of hospital-acquired anemia in MI patients because blood draws have been associated with increased need for transfusions in this patient population. The researchers used information from an electronic medical record database that detailed the frequency and type of laboratory testing as well as patients’ hemoglobin levels throughout hospitalization for acute MI. The database covered 57 hospitals during a recent 8-year period.

The study cohort was composed of all patients with acute MI, excluding those who already had anemia at admission and those who underwent coronary artery bypass grafting, because both the etiology and outcomes of anemia differ from those of non-CABG patients.

The data did not include exact amounts of blood drawn for every test. The investigators estimated these amounts from the types of tests that were run, assuming that only the minimal blood volume needed to run the required tests was drawn and that no blood was wasted at the blood draws.

Twenty percent of the study cohort (3,551 patients) developed moderate to severe anemia during hospitalization. Mean hemoglobin values declined in all patients, but they declined to a greater degree in those who developed anemia (–3.9 g/dL), compared with patients who didn’t develop anemia (–1.6 g/dL).

"The estimated mean blood loss from phlebotomy was nearly 100 mL higher over the course of hospitalization among patients who developed moderate to severe anemia, compared with those who did not (173.8 mL vs. 83.5 mL)," the investigators said (Arch. Intern Med. 2011; [doi:10.1001/archinternmed.2011.361]).

The average amount of blood drawn for laboratory testing varied significantly across hospitals, from a low of 53 mL to a high of 109.6 mL. The amount of blood typically drawn at a hospital significantly correlated with the incidence of anemia in its patients.

In a preliminary analysis, every 50 mL of blood drawn was associated with an 18% increase in the risk of hospital-acquired anemia. That risk persisted and remained robust after the data were adjusted to account for potential confounders.

When the data were broken down by day of hospitalization, the risk of developing anemia was highest on the first hospital day (10.5%), then remained relatively constant at 2.8%-4.5% through 10 days of hospitalization.

"Since most diagnostic evaluation and therapeutic interventions occur early during acute MI hospitalization, it is likely that much of the blood taken later during hospitalization represents routine, scheduled laboratory draws that could lead to ongoing blood loss." Indeed, blood loss was particularly high among patients who had longer hospital stays.

Several factors contribute to the development of hospital-acquired anemia. Some of these are not modifiable, such as patient age and sex, the presence of chronic kidney disease, and acute inflammation. But one factor that is clearly under the control of health care providers is minimization of phlebotomy, Dr. Salisbury and his associates said.

This study was retrospective and observational and so could not establish causality. Prospective randomized trials are needed to establish that the blood draws caused the anemia, as well as to determine whether strategies that limit both the number of blood draws and the volume of blood removed for diagnostic testing can prevent hospital-acquired anemia and improve clinical outcomes, they noted.

Dr. Salisbury and two associates were funded in part by an award from the American Heart Association Pharmaceutical Round Table. The investigators reported ties to numerous drug companies.

Blood loss from diagnostic blood testing during hospitalization is substantial and has been linked to anemia in patients with acute myocardial infarction, according to a study published online Aug. 8 in the Archives of Internal Medicine.

In a study of 17,676 MI patients at 57 U.S. hospitals, 1 in 5 patients developed moderate to severe hospital-acquired anemia, and they had a mean estimated phlebotomy volume of 173.8 mL – the equivalent of half a unit of whole blood. Twelve percent of the study subjects lost more than 300 mL to blood draws during the course of their hospitalization, said Dr. Adam C. Salisbury of Saint Luke’s Mid America Heart and Vascular Institute, Kansas City, Mo., and his associates.

Photo (c) Pearl Jackson/iStock.com

"Our findings are likely generalizable to other populations of seriously ill medical patients," they noted.

If further research establishes that minimizing blood loss from phlebotomy prevents anemia and improves patient outcomes, there would be broad implications for all hospitalized patients. Strategies to minimize blood loss, such as using pediatric instead of adult blood tubes or filling standard 4-mL adult tubes with only 1-2 mL of blood, would be widely adopted, Dr. Salisbury and his colleagues added.

They explored the relationship between diagnostic blood testing and the risk of hospital-acquired anemia in MI patients because blood draws have been associated with increased need for transfusions in this patient population. The researchers used information from an electronic medical record database that detailed the frequency and type of laboratory testing as well as patients’ hemoglobin levels throughout hospitalization for acute MI. The database covered 57 hospitals during a recent 8-year period.

The study cohort was composed of all patients with acute MI, excluding those who already had anemia at admission and those who underwent coronary artery bypass grafting, because both the etiology and outcomes of anemia differ from those of non-CABG patients.

The data did not include exact amounts of blood drawn for every test. The investigators estimated these amounts from the types of tests that were run, assuming that only the minimal blood volume needed to run the required tests was drawn and that no blood was wasted at the blood draws.

Twenty percent of the study cohort (3,551 patients) developed moderate to severe anemia during hospitalization. Mean hemoglobin values declined in all patients, but they declined to a greater degree in those who developed anemia (–3.9 g/dL), compared with patients who didn’t develop anemia (–1.6 g/dL).

"The estimated mean blood loss from phlebotomy was nearly 100 mL higher over the course of hospitalization among patients who developed moderate to severe anemia, compared with those who did not (173.8 mL vs. 83.5 mL)," the investigators said (Arch. Intern Med. 2011; [doi:10.1001/archinternmed.2011.361]).

The average amount of blood drawn for laboratory testing varied significantly across hospitals, from a low of 53 mL to a high of 109.6 mL. The amount of blood typically drawn at a hospital significantly correlated with the incidence of anemia in its patients.

In a preliminary analysis, every 50 mL of blood drawn was associated with an 18% increase in the risk of hospital-acquired anemia. That risk persisted and remained robust after the data were adjusted to account for potential confounders.

When the data were broken down by day of hospitalization, the risk of developing anemia was highest on the first hospital day (10.5%), then remained relatively constant at 2.8%-4.5% through 10 days of hospitalization.

"Since most diagnostic evaluation and therapeutic interventions occur early during acute MI hospitalization, it is likely that much of the blood taken later during hospitalization represents routine, scheduled laboratory draws that could lead to ongoing blood loss." Indeed, blood loss was particularly high among patients who had longer hospital stays.

Several factors contribute to the development of hospital-acquired anemia. Some of these are not modifiable, such as patient age and sex, the presence of chronic kidney disease, and acute inflammation. But one factor that is clearly under the control of health care providers is minimization of phlebotomy, Dr. Salisbury and his associates said.

This study was retrospective and observational and so could not establish causality. Prospective randomized trials are needed to establish that the blood draws caused the anemia, as well as to determine whether strategies that limit both the number of blood draws and the volume of blood removed for diagnostic testing can prevent hospital-acquired anemia and improve clinical outcomes, they noted.

Dr. Salisbury and two associates were funded in part by an award from the American Heart Association Pharmaceutical Round Table. The investigators reported ties to numerous drug companies.

Blood loss from diagnostic blood testing during hospitalization is substantial and has been linked to anemia in patients with acute myocardial infarction, according to a study published online Aug. 8 in the Archives of Internal Medicine.

In a study of 17,676 MI patients at 57 U.S. hospitals, 1 in 5 patients developed moderate to severe hospital-acquired anemia, and they had a mean estimated phlebotomy volume of 173.8 mL – the equivalent of half a unit of whole blood. Twelve percent of the study subjects lost more than 300 mL to blood draws during the course of their hospitalization, said Dr. Adam C. Salisbury of Saint Luke’s Mid America Heart and Vascular Institute, Kansas City, Mo., and his associates.

Photo (c) Pearl Jackson/iStock.com

"Our findings are likely generalizable to other populations of seriously ill medical patients," they noted.

If further research establishes that minimizing blood loss from phlebotomy prevents anemia and improves patient outcomes, there would be broad implications for all hospitalized patients. Strategies to minimize blood loss, such as using pediatric instead of adult blood tubes or filling standard 4-mL adult tubes with only 1-2 mL of blood, would be widely adopted, Dr. Salisbury and his colleagues added.

They explored the relationship between diagnostic blood testing and the risk of hospital-acquired anemia in MI patients because blood draws have been associated with increased need for transfusions in this patient population. The researchers used information from an electronic medical record database that detailed the frequency and type of laboratory testing as well as patients’ hemoglobin levels throughout hospitalization for acute MI. The database covered 57 hospitals during a recent 8-year period.

The study cohort was composed of all patients with acute MI, excluding those who already had anemia at admission and those who underwent coronary artery bypass grafting, because both the etiology and outcomes of anemia differ from those of non-CABG patients.

The data did not include exact amounts of blood drawn for every test. The investigators estimated these amounts from the types of tests that were run, assuming that only the minimal blood volume needed to run the required tests was drawn and that no blood was wasted at the blood draws.

Twenty percent of the study cohort (3,551 patients) developed moderate to severe anemia during hospitalization. Mean hemoglobin values declined in all patients, but they declined to a greater degree in those who developed anemia (–3.9 g/dL), compared with patients who didn’t develop anemia (–1.6 g/dL).

"The estimated mean blood loss from phlebotomy was nearly 100 mL higher over the course of hospitalization among patients who developed moderate to severe anemia, compared with those who did not (173.8 mL vs. 83.5 mL)," the investigators said (Arch. Intern Med. 2011; [doi:10.1001/archinternmed.2011.361]).

The average amount of blood drawn for laboratory testing varied significantly across hospitals, from a low of 53 mL to a high of 109.6 mL. The amount of blood typically drawn at a hospital significantly correlated with the incidence of anemia in its patients.

In a preliminary analysis, every 50 mL of blood drawn was associated with an 18% increase in the risk of hospital-acquired anemia. That risk persisted and remained robust after the data were adjusted to account for potential confounders.

When the data were broken down by day of hospitalization, the risk of developing anemia was highest on the first hospital day (10.5%), then remained relatively constant at 2.8%-4.5% through 10 days of hospitalization.

"Since most diagnostic evaluation and therapeutic interventions occur early during acute MI hospitalization, it is likely that much of the blood taken later during hospitalization represents routine, scheduled laboratory draws that could lead to ongoing blood loss." Indeed, blood loss was particularly high among patients who had longer hospital stays.

Several factors contribute to the development of hospital-acquired anemia. Some of these are not modifiable, such as patient age and sex, the presence of chronic kidney disease, and acute inflammation. But one factor that is clearly under the control of health care providers is minimization of phlebotomy, Dr. Salisbury and his associates said.

This study was retrospective and observational and so could not establish causality. Prospective randomized trials are needed to establish that the blood draws caused the anemia, as well as to determine whether strategies that limit both the number of blood draws and the volume of blood removed for diagnostic testing can prevent hospital-acquired anemia and improve clinical outcomes, they noted.

Dr. Salisbury and two associates were funded in part by an award from the American Heart Association Pharmaceutical Round Table. The investigators reported ties to numerous drug companies.

Aggressive glycemic control in diabetic patients undergoing coronary artery bypass graft surgery resulted in a sharp upswing in hypoglycemic events while providing no advantage in clinical cardiovascular outcomes, compared with moderate control, according to a randomized, controlled trial.

The impetus for this trial was the fact that the optimal blood glucose level in diabetic patients undergoing CABG surgery isn’t known, according to Dr. Harold L. Lazar. The Society of Thoracic Surgeons recommends that blood glucose be kept below 180 mg/dL during cardiac surgery and afterwards in the ICU (Ann. Thorac. Surg. 2009;87:663-9).

This recommendation is based on solid evidence of benefit; for example, a previous study by Dr. Lazar and his coworkers showed that maintaining blood glucose in the 120-180 mg/dL range in diabetic CABG patients resulted in less atrial fibrillation, fewer sternal wound infections, shorter hospital stays, better left ventricular function, and increased 5-year survival, compared with diabetic patients whose blood glucose was greater than 180 mg/dL (Circulation 2004;109:1497-502).

However, there have subsequently been conflicting reports as to whether maintaining blood glucose levels even lower (below 120 mg/dL) provides added benefit or might actually be harmful.

In the current study, 82 CABG patients with diabetes were randomized to moderate glycemic control if they had a blood glucose level of 120-180 mg/dL, or aggressive control if they had a blood glucose of 90-120 mg/dL. Levels were maintained using continuous intravenous insulin solutions, starting at the induction of anesthesia and continuing for 18 hours after surgery. All patients were on standard cardioprotective medications, including a beta-blocker, statin, and aspirin.

The moderate-control group achieved a mean blood glucose of 135 mg/dL, compared with 103 mg/dL in the tight-control group, Dr. Lazar said at the annual meeting of the American Surgical Association, where he presented the study results.

The primary end point was the 30-day rate of major adverse events, a composite that included death, MI, cerebrovascular accidents, atrial fibrillation, and deep sternal infections. The rate was 40% in the moderate-control group and 35% with aggressive glycemic control, a nonsignificant difference. Rates of each of the individual components of the composite end point were similar in the two groups as well. Nor did the two study arms differ significantly in secondary end points, including time on the ventilator, weight gain, need for inotropic support, or length of hospital or ICU stay, said Dr. Lazar of Boston Medical Center.

One or more hypoglycemic events were experienced by 10% of the moderate-control group vs. 75% of the aggressively managed group, although none of these episodes resulted in a neurologic event.

There was a trend for serum free fatty acid levels (a surrogate marker for a systemic inflammatory response) to be lower in the aggressive-control group than in the moderate-control group when they were measured 18 hours postoperatively.

Audience members questioned whether the 82-patient trial was powered sufficiently to draw firm conclusions regarding major adverse cardiovascular event rates. Dr. Lazar agreed that this is a legitimate concern. He said long-term follow-up of the study participants is planned to determine whether the lower free fatty acid levels in the aggressive glycemic control group will eventually be reflected in better graft patency and fewer ischemic events.

Dr. Lazar declared having no financial conflicts.

Aggressive glycemic control in diabetic patients undergoing coronary artery bypass graft surgery resulted in a sharp upswing in hypoglycemic events while providing no advantage in clinical cardiovascular outcomes, compared with moderate control, according to a randomized, controlled trial.

The impetus for this trial was the fact that the optimal blood glucose level in diabetic patients undergoing CABG surgery isn’t known, according to Dr. Harold L. Lazar. The Society of Thoracic Surgeons recommends that blood glucose be kept below 180 mg/dL during cardiac surgery and afterwards in the ICU (Ann. Thorac. Surg. 2009;87:663-9).

This recommendation is based on solid evidence of benefit; for example, a previous study by Dr. Lazar and his coworkers showed that maintaining blood glucose in the 120-180 mg/dL range in diabetic CABG patients resulted in less atrial fibrillation, fewer sternal wound infections, shorter hospital stays, better left ventricular function, and increased 5-year survival, compared with diabetic patients whose blood glucose was greater than 180 mg/dL (Circulation 2004;109:1497-502).

However, there have subsequently been conflicting reports as to whether maintaining blood glucose levels even lower (below 120 mg/dL) provides added benefit or might actually be harmful.

In the current study, 82 CABG patients with diabetes were randomized to moderate glycemic control if they had a blood glucose level of 120-180 mg/dL, or aggressive control if they had a blood glucose of 90-120 mg/dL. Levels were maintained using continuous intravenous insulin solutions, starting at the induction of anesthesia and continuing for 18 hours after surgery. All patients were on standard cardioprotective medications, including a beta-blocker, statin, and aspirin.

The moderate-control group achieved a mean blood glucose of 135 mg/dL, compared with 103 mg/dL in the tight-control group, Dr. Lazar said at the annual meeting of the American Surgical Association, where he presented the study results.

The primary end point was the 30-day rate of major adverse events, a composite that included death, MI, cerebrovascular accidents, atrial fibrillation, and deep sternal infections. The rate was 40% in the moderate-control group and 35% with aggressive glycemic control, a nonsignificant difference. Rates of each of the individual components of the composite end point were similar in the two groups as well. Nor did the two study arms differ significantly in secondary end points, including time on the ventilator, weight gain, need for inotropic support, or length of hospital or ICU stay, said Dr. Lazar of Boston Medical Center.

One or more hypoglycemic events were experienced by 10% of the moderate-control group vs. 75% of the aggressively managed group, although none of these episodes resulted in a neurologic event.

There was a trend for serum free fatty acid levels (a surrogate marker for a systemic inflammatory response) to be lower in the aggressive-control group than in the moderate-control group when they were measured 18 hours postoperatively.

Audience members questioned whether the 82-patient trial was powered sufficiently to draw firm conclusions regarding major adverse cardiovascular event rates. Dr. Lazar agreed that this is a legitimate concern. He said long-term follow-up of the study participants is planned to determine whether the lower free fatty acid levels in the aggressive glycemic control group will eventually be reflected in better graft patency and fewer ischemic events.

Dr. Lazar declared having no financial conflicts.

Aggressive glycemic control in diabetic patients undergoing coronary artery bypass graft surgery resulted in a sharp upswing in hypoglycemic events while providing no advantage in clinical cardiovascular outcomes, compared with moderate control, according to a randomized, controlled trial.

The impetus for this trial was the fact that the optimal blood glucose level in diabetic patients undergoing CABG surgery isn’t known, according to Dr. Harold L. Lazar. The Society of Thoracic Surgeons recommends that blood glucose be kept below 180 mg/dL during cardiac surgery and afterwards in the ICU (Ann. Thorac. Surg. 2009;87:663-9).

This recommendation is based on solid evidence of benefit; for example, a previous study by Dr. Lazar and his coworkers showed that maintaining blood glucose in the 120-180 mg/dL range in diabetic CABG patients resulted in less atrial fibrillation, fewer sternal wound infections, shorter hospital stays, better left ventricular function, and increased 5-year survival, compared with diabetic patients whose blood glucose was greater than 180 mg/dL (Circulation 2004;109:1497-502).

However, there have subsequently been conflicting reports as to whether maintaining blood glucose levels even lower (below 120 mg/dL) provides added benefit or might actually be harmful.

In the current study, 82 CABG patients with diabetes were randomized to moderate glycemic control if they had a blood glucose level of 120-180 mg/dL, or aggressive control if they had a blood glucose of 90-120 mg/dL. Levels were maintained using continuous intravenous insulin solutions, starting at the induction of anesthesia and continuing for 18 hours after surgery. All patients were on standard cardioprotective medications, including a beta-blocker, statin, and aspirin.

The moderate-control group achieved a mean blood glucose of 135 mg/dL, compared with 103 mg/dL in the tight-control group, Dr. Lazar said at the annual meeting of the American Surgical Association, where he presented the study results.

The primary end point was the 30-day rate of major adverse events, a composite that included death, MI, cerebrovascular accidents, atrial fibrillation, and deep sternal infections. The rate was 40% in the moderate-control group and 35% with aggressive glycemic control, a nonsignificant difference. Rates of each of the individual components of the composite end point were similar in the two groups as well. Nor did the two study arms differ significantly in secondary end points, including time on the ventilator, weight gain, need for inotropic support, or length of hospital or ICU stay, said Dr. Lazar of Boston Medical Center.

One or more hypoglycemic events were experienced by 10% of the moderate-control group vs. 75% of the aggressively managed group, although none of these episodes resulted in a neurologic event.

There was a trend for serum free fatty acid levels (a surrogate marker for a systemic inflammatory response) to be lower in the aggressive-control group than in the moderate-control group when they were measured 18 hours postoperatively.

Audience members questioned whether the 82-patient trial was powered sufficiently to draw firm conclusions regarding major adverse cardiovascular event rates. Dr. Lazar agreed that this is a legitimate concern. He said long-term follow-up of the study participants is planned to determine whether the lower free fatty acid levels in the aggressive glycemic control group will eventually be reflected in better graft patency and fewer ischemic events.

Dr. Lazar declared having no financial conflicts.

DANA POINT, CALIF. – Scar formation and fibrosis can be reduced by altering the mechanical environment of wounds, results from a phase I study found.

At the Summit in Aesthetic Medicine, sponsored by Skin Disease Education Foundation (SDEF), Dr. Geoffrey C. Gurtner presented findings from a study in which nine patients undergoing elective abdominal surgery were treated postoperatively with a stress-shielding polymer on one side while the other side was treated with standard wound care.

©Neodyne Biosciences, Inc

The device, manufactured by Neodyne Biosciences, looks like a Band-Aid strip and is stretched over the incision after sutures are removed. It conforms to the wound and adheres to skin, creating "a compressive region that has no level of mechanical stimulation or distractive strain," said Dr. Gurtner, professor of surgery at Stanford (Calif.) University. "Essentially, you create stress risers in the unwounded skin and a mechanically privileged environment in the wounded skin."

A panel of three independent plastic surgeons reviewed 18 photos of the scars (nine treated, nine control) taken 6-12 months after surgery (Ann. Surg. 2011 May 19 [doi: 10.1097/SLA.0b013e318220b159]). They used a visual analog scale (VAS) that ranged from 0 (very good scar) to 100 (very poor hypertrophic scar).

Dr. Gurtner reported that the average VAS score in the treated group was 18.6, while the average VAS score in the control group was 50.5, a difference that was statistically significant (P = .0039). "In none of the cases was the treated scar worse than the control scar, which I think is different than some of the biologic agents we’ve seen over the last few years," he said.*

A panel of lay persons who reviewed the photos reported similar results that favored the treated group (P = .004).

In earlier mouse studies of wound environment manipulation, Dr. Gurtner and his associates found that focal adhesion kinase (FAK) is a critical regulator in the formation of hypertrophic scars. He described FAK as "a molecule that exists on the inner surface of cell membranes and transmits forces that are set in the external extracellular matrix to the inside of the cell. FAK transmits those forces into biological or biochemical cues that then turn on genes in the nucleus and make the cells do different things. This seems to be a very important molecule in the ability of us to produce hypertrophic scars in mice. If you take out FAK, you can prevent hypertrophic scar formation."

FAK is a target that has been examined extensively in cancer, Dr. Gurtner said, suggesting that in the next few years, "We should have products that will not only be able to treat incision wounds but will also be able to treat large burn injuries. You need to fool the cells into thinking they’re in a different mechanical environment, either by using small molecule or pharmacologic blocking therapies such as fat inhibitors, or by using biomaterials that provide cues in a controlled way that minimize the amount of mechanical stimulation that the fibroblasts feel in the healing wound so as to mitigate the inflammation and subsequent fibrosis."

The study was supported by a Wallace H. Coulter Translational Partners Grant; the Armed Forces Institute of Regenerative Medicine; the Hagey Family Endowed Fund in Stem Cell Research and Regenerative Medicine; and the Oak Foundation. Neodyne Biosciences supplied the surgical dressings used in the study. Dr. Gurtner disclosed that he holds an equity interest in Neodyne.

SDEF and this news organization are owned by Elsevier.

*Correction 8/22/11: An earlier version of this story misstated the VAS scores for the two groups of patients.

DANA POINT, CALIF. – Scar formation and fibrosis can be reduced by altering the mechanical environment of wounds, results from a phase I study found.

At the Summit in Aesthetic Medicine, sponsored by Skin Disease Education Foundation (SDEF), Dr. Geoffrey C. Gurtner presented findings from a study in which nine patients undergoing elective abdominal surgery were treated postoperatively with a stress-shielding polymer on one side while the other side was treated with standard wound care.

©Neodyne Biosciences, Inc

The device, manufactured by Neodyne Biosciences, looks like a Band-Aid strip and is stretched over the incision after sutures are removed. It conforms to the wound and adheres to skin, creating "a compressive region that has no level of mechanical stimulation or distractive strain," said Dr. Gurtner, professor of surgery at Stanford (Calif.) University. "Essentially, you create stress risers in the unwounded skin and a mechanically privileged environment in the wounded skin."

A panel of three independent plastic surgeons reviewed 18 photos of the scars (nine treated, nine control) taken 6-12 months after surgery (Ann. Surg. 2011 May 19 [doi: 10.1097/SLA.0b013e318220b159]). They used a visual analog scale (VAS) that ranged from 0 (very good scar) to 100 (very poor hypertrophic scar).

Dr. Gurtner reported that the average VAS score in the treated group was 18.6, while the average VAS score in the control group was 50.5, a difference that was statistically significant (P = .0039). "In none of the cases was the treated scar worse than the control scar, which I think is different than some of the biologic agents we’ve seen over the last few years," he said.*

A panel of lay persons who reviewed the photos reported similar results that favored the treated group (P = .004).

In earlier mouse studies of wound environment manipulation, Dr. Gurtner and his associates found that focal adhesion kinase (FAK) is a critical regulator in the formation of hypertrophic scars. He described FAK as "a molecule that exists on the inner surface of cell membranes and transmits forces that are set in the external extracellular matrix to the inside of the cell. FAK transmits those forces into biological or biochemical cues that then turn on genes in the nucleus and make the cells do different things. This seems to be a very important molecule in the ability of us to produce hypertrophic scars in mice. If you take out FAK, you can prevent hypertrophic scar formation."

FAK is a target that has been examined extensively in cancer, Dr. Gurtner said, suggesting that in the next few years, "We should have products that will not only be able to treat incision wounds but will also be able to treat large burn injuries. You need to fool the cells into thinking they’re in a different mechanical environment, either by using small molecule or pharmacologic blocking therapies such as fat inhibitors, or by using biomaterials that provide cues in a controlled way that minimize the amount of mechanical stimulation that the fibroblasts feel in the healing wound so as to mitigate the inflammation and subsequent fibrosis."

The study was supported by a Wallace H. Coulter Translational Partners Grant; the Armed Forces Institute of Regenerative Medicine; the Hagey Family Endowed Fund in Stem Cell Research and Regenerative Medicine; and the Oak Foundation. Neodyne Biosciences supplied the surgical dressings used in the study. Dr. Gurtner disclosed that he holds an equity interest in Neodyne.

SDEF and this news organization are owned by Elsevier.

*Correction 8/22/11: An earlier version of this story misstated the VAS scores for the two groups of patients.

DANA POINT, CALIF. – Scar formation and fibrosis can be reduced by altering the mechanical environment of wounds, results from a phase I study found.

At the Summit in Aesthetic Medicine, sponsored by Skin Disease Education Foundation (SDEF), Dr. Geoffrey C. Gurtner presented findings from a study in which nine patients undergoing elective abdominal surgery were treated postoperatively with a stress-shielding polymer on one side while the other side was treated with standard wound care.

©Neodyne Biosciences, Inc

The device, manufactured by Neodyne Biosciences, looks like a Band-Aid strip and is stretched over the incision after sutures are removed. It conforms to the wound and adheres to skin, creating "a compressive region that has no level of mechanical stimulation or distractive strain," said Dr. Gurtner, professor of surgery at Stanford (Calif.) University. "Essentially, you create stress risers in the unwounded skin and a mechanically privileged environment in the wounded skin."

A panel of three independent plastic surgeons reviewed 18 photos of the scars (nine treated, nine control) taken 6-12 months after surgery (Ann. Surg. 2011 May 19 [doi: 10.1097/SLA.0b013e318220b159]). They used a visual analog scale (VAS) that ranged from 0 (very good scar) to 100 (very poor hypertrophic scar).

Dr. Gurtner reported that the average VAS score in the treated group was 18.6, while the average VAS score in the control group was 50.5, a difference that was statistically significant (P = .0039). "In none of the cases was the treated scar worse than the control scar, which I think is different than some of the biologic agents we’ve seen over the last few years," he said.*

A panel of lay persons who reviewed the photos reported similar results that favored the treated group (P = .004).

In earlier mouse studies of wound environment manipulation, Dr. Gurtner and his associates found that focal adhesion kinase (FAK) is a critical regulator in the formation of hypertrophic scars. He described FAK as "a molecule that exists on the inner surface of cell membranes and transmits forces that are set in the external extracellular matrix to the inside of the cell. FAK transmits those forces into biological or biochemical cues that then turn on genes in the nucleus and make the cells do different things. This seems to be a very important molecule in the ability of us to produce hypertrophic scars in mice. If you take out FAK, you can prevent hypertrophic scar formation."

FAK is a target that has been examined extensively in cancer, Dr. Gurtner said, suggesting that in the next few years, "We should have products that will not only be able to treat incision wounds but will also be able to treat large burn injuries. You need to fool the cells into thinking they’re in a different mechanical environment, either by using small molecule or pharmacologic blocking therapies such as fat inhibitors, or by using biomaterials that provide cues in a controlled way that minimize the amount of mechanical stimulation that the fibroblasts feel in the healing wound so as to mitigate the inflammation and subsequent fibrosis."

The study was supported by a Wallace H. Coulter Translational Partners Grant; the Armed Forces Institute of Regenerative Medicine; the Hagey Family Endowed Fund in Stem Cell Research and Regenerative Medicine; and the Oak Foundation. Neodyne Biosciences supplied the surgical dressings used in the study. Dr. Gurtner disclosed that he holds an equity interest in Neodyne.

SDEF and this news organization are owned by Elsevier.

*Correction 8/22/11: An earlier version of this story misstated the VAS scores for the two groups of patients.

VANCOUVER, B.C. – Anastomotic leaks after colectomy are more likely to be fatal in patients with preoperative hyperglycemia, based on the results of a database analysis.

Patients with diabetes were not at increased risk of an anastomotic leak. When leaks occurred, however, the associated mortality rate was 25% among those with diabetes and 3.6% among those without diabetes, Dr. Matthew Ziegler reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Dr. Ziegler, of the William Beaumont Hospital, Royal Oak, Mich., and his colleagues drew their findings from the database of the Michigan Surgical Quality Collaborative. The database included 3,977 patients who had a colectomy from February 2008 to March 2010. Of these, 700 were known to have diabetes. The researchers used a fasting blood glucose value greater than 140 mg/dL as the definition of hyperglycemia.

Fasting glucose values were tested preoperatively in 85% of the patients; 14% had hyperglycemia, and just over half of those patients had diabetes.

At 30 days after surgery, overall mortality was 5.5% for those with diabetes and 2.9% in those without diabetes. Mortality was 8%, which was significantly higher, in the nondiabetic patients with preoperative fasting hyperglycemia.

Parsing the data further, Dr. Ziegler and his colleagues found two risk factors – preoperative steroid use and emergent surgery – that were associated with anastomotic leaks in patients with diabetes. "This may be important, especially in colectomy patients, because of the high morbidity," he said. Dr. Ziegler added that he would hesitate to perform a colectomy on a patient with diabetes who is on preoperative steroids.

Many Americans have diabetes or are on the road to acquiring that disease, said Dr. Ziegler. In addition to the 18 million diagnosed with diabetes in the United States, an estimated 7 million have not yet been diagnosed and 79 million have prediabetes, with elevated fasting glucose or hemoglobin A_1c levels.

"Certainly [the findings] merit more study, and improved preoperative screening is needed to better identify and treat this complicated patient population," he said.

Dr. Ziegler said that his hospital has stepped up screening efforts to include preoperative fasting glucose levels and HbA₁c levels. "We also have just instituted a so-called ‘sugar nurse’ who is a nurse specialist who meets with patients preoperatively and works on their glycemic management perioperatively with hopefully better outcomes."

VANCOUVER, B.C. – Anastomotic leaks after colectomy are more likely to be fatal in patients with preoperative hyperglycemia, based on the results of a database analysis.

Patients with diabetes were not at increased risk of an anastomotic leak. When leaks occurred, however, the associated mortality rate was 25% among those with diabetes and 3.6% among those without diabetes, Dr. Matthew Ziegler reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Dr. Ziegler, of the William Beaumont Hospital, Royal Oak, Mich., and his colleagues drew their findings from the database of the Michigan Surgical Quality Collaborative. The database included 3,977 patients who had a colectomy from February 2008 to March 2010. Of these, 700 were known to have diabetes. The researchers used a fasting blood glucose value greater than 140 mg/dL as the definition of hyperglycemia.

Fasting glucose values were tested preoperatively in 85% of the patients; 14% had hyperglycemia, and just over half of those patients had diabetes.

At 30 days after surgery, overall mortality was 5.5% for those with diabetes and 2.9% in those without diabetes. Mortality was 8%, which was significantly higher, in the nondiabetic patients with preoperative fasting hyperglycemia.

Parsing the data further, Dr. Ziegler and his colleagues found two risk factors – preoperative steroid use and emergent surgery – that were associated with anastomotic leaks in patients with diabetes. "This may be important, especially in colectomy patients, because of the high morbidity," he said. Dr. Ziegler added that he would hesitate to perform a colectomy on a patient with diabetes who is on preoperative steroids.

Many Americans have diabetes or are on the road to acquiring that disease, said Dr. Ziegler. In addition to the 18 million diagnosed with diabetes in the United States, an estimated 7 million have not yet been diagnosed and 79 million have prediabetes, with elevated fasting glucose or hemoglobin A_1c levels.

"Certainly [the findings] merit more study, and improved preoperative screening is needed to better identify and treat this complicated patient population," he said.

Dr. Ziegler said that his hospital has stepped up screening efforts to include preoperative fasting glucose levels and HbA₁c levels. "We also have just instituted a so-called ‘sugar nurse’ who is a nurse specialist who meets with patients preoperatively and works on their glycemic management perioperatively with hopefully better outcomes."

VANCOUVER, B.C. – Anastomotic leaks after colectomy are more likely to be fatal in patients with preoperative hyperglycemia, based on the results of a database analysis.

Patients with diabetes were not at increased risk of an anastomotic leak. When leaks occurred, however, the associated mortality rate was 25% among those with diabetes and 3.6% among those without diabetes, Dr. Matthew Ziegler reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Dr. Ziegler, of the William Beaumont Hospital, Royal Oak, Mich., and his colleagues drew their findings from the database of the Michigan Surgical Quality Collaborative. The database included 3,977 patients who had a colectomy from February 2008 to March 2010. Of these, 700 were known to have diabetes. The researchers used a fasting blood glucose value greater than 140 mg/dL as the definition of hyperglycemia.

Fasting glucose values were tested preoperatively in 85% of the patients; 14% had hyperglycemia, and just over half of those patients had diabetes.

At 30 days after surgery, overall mortality was 5.5% for those with diabetes and 2.9% in those without diabetes. Mortality was 8%, which was significantly higher, in the nondiabetic patients with preoperative fasting hyperglycemia.

Parsing the data further, Dr. Ziegler and his colleagues found two risk factors – preoperative steroid use and emergent surgery – that were associated with anastomotic leaks in patients with diabetes. "This may be important, especially in colectomy patients, because of the high morbidity," he said. Dr. Ziegler added that he would hesitate to perform a colectomy on a patient with diabetes who is on preoperative steroids.

Many Americans have diabetes or are on the road to acquiring that disease, said Dr. Ziegler. In addition to the 18 million diagnosed with diabetes in the United States, an estimated 7 million have not yet been diagnosed and 79 million have prediabetes, with elevated fasting glucose or hemoglobin A_1c levels.

"Certainly [the findings] merit more study, and improved preoperative screening is needed to better identify and treat this complicated patient population," he said.

Dr. Ziegler said that his hospital has stepped up screening efforts to include preoperative fasting glucose levels and HbA₁c levels. "We also have just instituted a so-called ‘sugar nurse’ who is a nurse specialist who meets with patients preoperatively and works on their glycemic management perioperatively with hopefully better outcomes."

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.