Mark K. Huntington, MD, PhD, FAAFP

CASE Charlie H, an elderly man who has been your patient for more than 10 years, is scheduled for inguinal hernia repair, and has come in for a preoperative evaluation. Based on his medical history and a physical examination, you identify several risk factors for surgical complications: a low functional capacity (<4 METS), obesity (BMI=39), advanced age (70 years), and type 2 diabetes (well controlled). What should you write in your consultation note about Charlie’s perioperative risks, and what interventions should you institute—or recommend—to mitigate his risk?

A preoperative consult, a service that family physicians are well positioned to provide, requires a thorough and systematic approach. But because of time pressures—as well as a dearth of perioperative templates, guidelines, and checklists—a cursory history and physical exam often takes the place of a comprehensive evaluation.

A thorough medical history is the most valuable tool of a physician doing a preop consult, but a comprehensive evaluation also involves the assessment of perioperative risk factors, ancillary tests to consider, and interventions to recommend to mitigate risks. Although various published guidelines address specific systems, there are few places where family physicians can find a complete toolkit. The text and tables that follow, which form the core of a comprehensive resource initially compiled to help our residents conduct clear and effective preoperative consults, will help you safeguard your patients.

A system-by-system review starts with the heart

The vast majority of perioperative problems fall into a handful of categories: cardiac, pulmonary, renal, infectious, and hematologic complications (TABLE 1). When a surgeon requests a preoperative evaluation, however, the patient’s cardiac status is generally the primary concern. This is also the portion of the preop consult with the most formally structured guidelines; those issued by the American College of Cardiology and American Heart Association (ACC/AHA) are the most widely used.¹ Initially based primarily on expert opinion, the ACC/AHA guidelines are increasingly evidence-based (http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.109.192690).^1,2 These guidelines address the evaluation of patients for noncardiac surgery. Both cardiac surgery and emergent operations are beyond the scope of the guidelines, and are not addressed here.

Patients with unstable coronary syndromes—eg, unstable angina or myocardial infarction (MI) within the past 30 days, decompensated heart failure (HF), significant arrhythmias, or severe valvular disease—face an increased risk of perioperative morbidity and mortality. To reduce the risk, such patients require optimization of the underlying condition before undergoing elective surgery.¹

Is additional cardiac testing necessary? Whether you’re assessing for cardiac status or other risks, for that matter, evidence supports the use of ancillary testing in only a small minority of surgical patients. A general rule of thumb—regardless of the system you’re assessing—is to consider adjunctive testing only if the outcome has the potential to alter patient management. Thus, exercise stress testing or resting electrocardiography (EKG), among other tests, may be considered on an individual basis (TABLE 2), but studies have failed to demonstrate improved outcomes with added testing of cardiac status on a routine basis.^5,6

Evidence is insufficient to make a firm recommendation regarding additional cardiac testing, even for patients with more than 3 clinical risk factors. Nonetheless, the ACC/AHA guidelines favor the use of adjunctive testing in such cases, especially for patients who are candidates for high-risk procedures, such as vascular surgery.¹

What’s the local standard of care? Studies to determine when further testing is beneficial and which tests would benefit which patients are ongoing. In the absence of definitive findings, it behooves primary care physicians to familiarize themselves with the practices and preferences of the cardiologists and anesthesiologists at the facility where the surgery will be performed and to follow the local standard of care.

TABLE 1
Identifying—and minimizing—perioperative risk

TABLE 2
When should you order these ancillary tests?*

Identify pulmonary risks with help from ACP
Postoperative pulmonary complications are as prevalent as cardiac complications, and contribute equally to morbidity, mortality, and length of stay. But pulmonary complications are better predictors of long-term mortality after surgery.⁷

There are several well-validated risk factors for increased perioperative pulmonary morbidity and mortality—HF, chronic obstructive pulmonary disease (COPD), advanced age, and the need for assistance with activities of daily living among them. In addition to identifying patient-specific risk factors, knowledge of the type of surgery planned will provide insight into procedure-specific risk factors (TABLE 1). The approach to the surgical pulmonary patient is addressed in an American College of Physicians (ACP) guideline published in 2006 and available at http://www.annals.org/content/144/8/575.full.pdf+html.⁷

What tests to consider? The ACP guideline is notable not only for its recommendations, but for the things that are not recommended but may nevertheless be considered the standard of care in some locales. Chest radiography and spirometry are 2 such examples. Although these tests may be appropriate on an individual basis for patients with a previous diagnosis of COPD or asthma, their routine use is of little value—and the ACP does not recommend them as part of a standard preop evaluation.⁷ Some laboratory tests may aid in risk stratification, however.

A serum albumin level <35 g/L is strongly associated with postop pulmonary complications.⁸ Checking levels in all patients suspected of hypoalbuminemia, including any patient with 1 or more pulmonary risk factors, is reasonable for a physician performing a preoperative evaluation. Consider checking blood urea nitrogen (BUN) levels, as well. Uremia (BUN >21 mg/dL) is also associated with increased pulmonary complications, although not as strongly as hypoalbuminemia.

Postpone or proceed? Acute conditions are another key consideration. An upper respiratory infection (URI) increases the risk of postoperative pulmonary complications, especially in children.^9,10 A simple algorithm offers guidance in deciding when to postpone surgery in pediatric patients with a URI:⁹

Recommend that it be delayed if the procedure involves general anesthesia and 1 or more of the following risk factors is present: asthma, a history of prematurity, copious secretions, a parent who smokes, planned use of an endotracheal tube, or a procedure involving the airway.

Surgery can proceed if symptoms of the infection are mild, general anesthesia is not required, or a risk/benefit analysis supports it. Considerations include the urgency of the procedure, whether the surgery has previously been postponed, the comfort level of the clinicians involved, and the distance the family must travel for the procedure.¹¹

If you recommend that surgery proceed as planned, suggest perioperative interventions to mitigate risk. Recommend that a laryngeal mask airway be used, if needed, in place of an endotracheal tube; that pulse oximetry monitoring occur; that good hydration and humidification of air be provided; and that the patient receive anticholinergic agents for secretions.

Other measures that have been shown to be effective in reducing perioperative pulmonary complications include deep breathing exercises (incentive spirometry) and the use of a nasogastric tube for those with postoperative emesis, intolerance of oral intake, or symptomatic abdominal distension.⁷ If your patient has risk factors for pulmonary complications, include a recommendation for a postop nasogastric tube in your preop consultation note. However, newer data indicating that patients had fewer pulmonary complications, a more rapid return of normal bowel function, no increased discomfort, and no increase in anastomotic leaks without a nasogastric tube^12,13 may lead to guideline revision.

A scoring system helps evaluate renal risk
Patients with CRF face increased risk of perioperative morbidity and mortality. But as long as the glomerular filtration rate (GFR) is >25 mL/min—which is only 25% of normal—surgery is generally well tolerated. As GFR drops to 10 to 15 mL/min, the rate of surgical complications rises rapidly, reaching 55% to 60%. For such patients, preoperative dialysis is worth considering.¹⁴

Postoperative acute kidney injury (AKI), as acute renal failure is now known,¹⁵ is associated with a 58% mortality rate.¹⁶ Fortunately, this complication develops in only about 1% of surgical patients.¹⁷ Both patient-specific risk factors (CRF, with creatinine >2.1 mg/dL; HF; diabetes, particularly being insulin dependent; age >60 years; jaundice) and procedure-specific risks (aortic, cardiovascular, or liver transplant surgery) help predict which surgical candidates face the highest risk.^16,18,19 Thakar et al have developed a scoring system to identify those at greatest risk for AKI.²⁰ (See “Cardiovascular surgery and acute kidney injury: Scoring the risk” at www.jfponline.com by clicking on “Before surgery: Have you done enough to mitigate risk?” and scrolling to the end.)

Minimize renal complications. Helping patients achieve good intravascular volume and osmolar status preoperatively will reduce their risk of renal complications. Other prophylactic measures: Minimize exposure to nephrotoxins (eg, nonsteroidal anti-inflammatory drugs or contrast media) to the extent possible. Consider evaluating the serum electrolyte and creatinine levels of patients with multiple risk factors to determine whether they can safely undergo surgery; some experts suggest preoperative urinalysis, as well.¹⁸

Patients with end-stage renal disease have very high perioperative morbidity.²¹ They are at increased risk for hyperkalemia, infection, hyper- and hypotension, bleeding, arrhythmias, and clotted fistulas, in descending order of incidence.¹⁸ Preoperative planning, including the need for dialysis before surgery, is necessary to manage these risks.

Risk of postop infection: Focusing on the foreseeable
Postoperative infections, both at the surgical site and remote from the incision, are a significant cause of morbidity and mortality. Pneumonia is among the most prominent remote infections associated with surgery,²² and early ambulation, deep breathing exercises, and tight glycemic control can greatly decrease the risk.

Surgical site infection (SSI) remains an important concern, occurring in 37% of cases.²³ Risk factors include hyperglycemia, malnutrition, perioperative steroid use, preexisting infections, tobacco smoking, peripheral vascular disease, advanced age, radiation therapy, blood transfusions, prolonged preoperative stay, preoperative shaving, hypothermia, hypoxia, length of operation, and postoperative incontinence.²⁴ While many of these risk factors are dependent on interventions in the operating room and recovery room or during subsequent hospitalization, it is important to address foreseeable risks as part of the preoperative evaluation.

Glycemic control is crucial. Perhaps the most well-documented risk for SSI is hyperglycemia—a common problem among hospitalized patients.¹⁶ Hyperglycemia impairs leukocyte and complement function,^25,26 thereby increasing risk of infectious complications. Tight glycemic control in the surgical patient, especially on the surgical intensive care unit, has been associated with improved outcomes.²⁷

Identify the presence of diabetes in the preoperative consult note, and adjust the patient’s medication regimen as needed, to help him or her achieve optimal glycemic control. In some cases, it may be necessary to delay nonurgent surgery until the patient achieves adequate control.

Malnutrition is another risk factor for SSI. For patients who are undernourished or morbidly obese, checking serum albumin levels may be beneficial. Supplementation for 1 to 2 weeks prior to surgery may decrease the risk of infection for patients who are undernourished;²⁸ for obese patients, weight loss is beneficial. Although significant preoperative weight loss may not be possible, it is important to list an elevated body mass index as a risk factor in the consultation note.

Corticosteroids, used to treat conditions such as COPD, inflammatory bowel disease, allergies, and autoimmune disorders, are another risk factor for perioperative infection. In addition to their effect on glycemic control, corticosteroids directly suppress the immune system. Whenever possible, they should be discontinued preoperatively. If this is not possible, call attention to the patient’s use of corticosteroids in the consultation note.

Preexisting infection presents the possibility of the spread of organisms to the surgical site and, whenever possible, surgery should be postponed until the infection resolves. If the patient has a history of prior infection or colonization with methicillin-resistant Staphylococcus aureus, be sure to include that in the consultation note, as well.

Leukocyte-containing blood product transfusions are associated with a 2-fold increase in some postop infectious complications.^29-31 This is in addition to the well-known risk of bloodborne pathogens associated with transfusions, and is yet another reason to avoid perioperative transfusions whenever possible.

Smoking impairs tissue oxygenation, which delays healing and increases risk of infection. Smoking cessation should be strongly encouraged at every preoperative consultation. Recommend nicotine replacement therapy even for patients who aren’t willing to quit altogether; point out that giving up cigarettes for just 30 days (or more) before surgery can decrease the likelihood of complications.²⁸

In addition to these identified risk factors, anything that compromises the immune status increases the risk of infection. Alcohol or drug abusers, chronic pain patients, transplant recipients, cancer patients taking immunosuppressants, postsplenectomy patients, and patients with HIV are all at increased risk. Identify any such conditions during your preoperative evaluation, and be sure to include them in your communication with the surgical team.

A common request in preop consults relates to bacterial endocarditis prophylaxis. Only an extremely small number of cases of infective endocarditis occur with dental procedures, however, so the benefits of antibiotic prophylaxis would be minimal, even if the prophylactic therapy were 100% effective.³² As a result, the ACC/AHA guidelines recommend prophylaxis for dental procedures only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis. Administration of antibiotics solely to prevent endocarditis is not recommended for patients undergoing genitourinary or gastrointestinal tract procedures.³²

Hematologic evaluation: Address risks of bleeding, clotting
Historically, a variety of tests have been employed in an effort to identify patients at risk for bleeding complications prior to surgery—including prothrombin time, partial thromboplastin time, platelet count, and bleeding time, or platelet function. While highly reproducible, automated, and inexpensive when considered individually, the cumulative cost of routine use of these tests is high.³³

A recent review of the literature indicates that, for surgical patients without synthetic liver dysfunction or a history of oral anticoagulant use, routine testing is of little value in the assessment of bleeding risk.³⁴ Patients with a negative bleeding history do not require routine coagulation screening prior to surgery.³⁵

Instead, use the medical history to identify risk factors for bleeding. These include excessive bruising, nosebleeds, prolonged bleeding after cuts, bleeding >3 minutes after brushing teeth, and heavy or prolonged menses (TABLE 1). Patients with a past medical history of liver disease; renal failure; hypersplenism; hematologic disease; collagen vascular disease; hemophilia or other inherited hemorrhagic disorder; gastrointestinal or urogenital blood loss; and severe bleeding after dental extraction, other surgery, or childbirth are also at heightened risk, as are those who take medications that affect hemostasis. Physical findings suggestive of risk include purpura, hematoma, jaundice, and signs of cirrhosis.³⁴

While laboratory testing is only appropriate to confirm those at risk in the subpopulation selected by the history and physical, here, as with other adjunctive testing, it is important to consider local standards and the preferences of the surgeon who requested the preop consult.

Treat anemia. Preoperative anemia is linked to adverse outcomes in surgical patients,³⁶ although it is not clear whether the anemia itself or the perioperative transfusions associated with the condition are at the root of the problem.³⁷ Macrocytic anemia may require treatment with vitamin B₁₂ and folate; iron deficiency anemia is treated with iron. Some physicians also recommend the use of erythropoietin starting 3 weeks prior to surgery for patients with normocytic anemia with hemoglobin <13 g/dL.^38,39

Thromboembolism risk. Excessive clotting is responsible for more perioperative complications than excessive bleeding. There is a high prevalence of venous thromboembolism (VTE) among surgical patients, with both patient- and procedure-specific risk factors. Although a variety of coagulopathies increase the baseline risk for VTE, routine laboratory screening of the general surgical population for thrombophilia is not recommended.^34,35

When risk factors are present based on both the patient’s medical history and the type of procedure, prophylactic measures may be needed (TABLE 3). Options include mechanical prophylaxis (graduated compression stockings and intermittent pneumatic devices) and chemoprophylaxis. Recommended for high-risk cases, such as patients undergoing orthopedic surgery that precludes early mobilization, chemoprophylaxis options include low-molecular-weight heparin, low-dose unfractionated heparin, fondaparinux (a synthetic factor Xa inhibitor), and vitamin K antagonists such as warfarin.⁴⁰ Aspirin alone is not recommended, as it has not been found to be an effective prophylaxis for VTE.

CASE After following this system-by-system review of your patient, Charlie H, you identify and explicitly communicate the following risk factors in your consultation note:

• Cardiovascular: type 2 diabetes, low functional capacity
• Pulmonary: advanced age
• Renal: advanced age
• Infectious: type 2 diabetes, advanced age, BMI=39
• Hematologic: advanced age, obesity

Based on these findings, you develop the following plan for Charlie H, detailed in the consultation note you submit to the surgical team:

• Continue home diabetes medications perioperatively, supplemented with a basal-bolus insulin regimen.
• Initiate incentive spirometry postoperatively; use an NG tube if postoperative nausea and vomiting occur.
• Maintain MAP >65 mm Hg.
• Institute aggressive early ambulation and use of graduated compression stockings for DVT prophylaxis.
  Submitted by ___________ on ________.

TABLE 3
Perioperative thromboembolism: Risk and prophylaxis

CORRESPONDENCE Mark K. Huntington, MD, PhD, FAAFP, Center for Family Medicine, 1115 East Twentieth Street, Sioux Falls, SD 57105; [email protected]

CASE Charlie H, an elderly man who has been your patient for more than 10 years, is scheduled for inguinal hernia repair, and has come in for a preoperative evaluation. Based on his medical history and a physical examination, you identify several risk factors for surgical complications: a low functional capacity (<4 METS), obesity (BMI=39), advanced age (70 years), and type 2 diabetes (well controlled). What should you write in your consultation note about Charlie’s perioperative risks, and what interventions should you institute—or recommend—to mitigate his risk?

A preoperative consult, a service that family physicians are well positioned to provide, requires a thorough and systematic approach. But because of time pressures—as well as a dearth of perioperative templates, guidelines, and checklists—a cursory history and physical exam often takes the place of a comprehensive evaluation.

A thorough medical history is the most valuable tool of a physician doing a preop consult, but a comprehensive evaluation also involves the assessment of perioperative risk factors, ancillary tests to consider, and interventions to recommend to mitigate risks. Although various published guidelines address specific systems, there are few places where family physicians can find a complete toolkit. The text and tables that follow, which form the core of a comprehensive resource initially compiled to help our residents conduct clear and effective preoperative consults, will help you safeguard your patients.

A system-by-system review starts with the heart

The vast majority of perioperative problems fall into a handful of categories: cardiac, pulmonary, renal, infectious, and hematologic complications (TABLE 1). When a surgeon requests a preoperative evaluation, however, the patient’s cardiac status is generally the primary concern. This is also the portion of the preop consult with the most formally structured guidelines; those issued by the American College of Cardiology and American Heart Association (ACC/AHA) are the most widely used.¹ Initially based primarily on expert opinion, the ACC/AHA guidelines are increasingly evidence-based (http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.109.192690).^1,2 These guidelines address the evaluation of patients for noncardiac surgery. Both cardiac surgery and emergent operations are beyond the scope of the guidelines, and are not addressed here.

Patients with unstable coronary syndromes—eg, unstable angina or myocardial infarction (MI) within the past 30 days, decompensated heart failure (HF), significant arrhythmias, or severe valvular disease—face an increased risk of perioperative morbidity and mortality. To reduce the risk, such patients require optimization of the underlying condition before undergoing elective surgery.¹

Is additional cardiac testing necessary? Whether you’re assessing for cardiac status or other risks, for that matter, evidence supports the use of ancillary testing in only a small minority of surgical patients. A general rule of thumb—regardless of the system you’re assessing—is to consider adjunctive testing only if the outcome has the potential to alter patient management. Thus, exercise stress testing or resting electrocardiography (EKG), among other tests, may be considered on an individual basis (TABLE 2), but studies have failed to demonstrate improved outcomes with added testing of cardiac status on a routine basis.^5,6

Evidence is insufficient to make a firm recommendation regarding additional cardiac testing, even for patients with more than 3 clinical risk factors. Nonetheless, the ACC/AHA guidelines favor the use of adjunctive testing in such cases, especially for patients who are candidates for high-risk procedures, such as vascular surgery.¹

What’s the local standard of care? Studies to determine when further testing is beneficial and which tests would benefit which patients are ongoing. In the absence of definitive findings, it behooves primary care physicians to familiarize themselves with the practices and preferences of the cardiologists and anesthesiologists at the facility where the surgery will be performed and to follow the local standard of care.

TABLE 1
Identifying—and minimizing—perioperative risk

TABLE 2
When should you order these ancillary tests?*

Identify pulmonary risks with help from ACP
Postoperative pulmonary complications are as prevalent as cardiac complications, and contribute equally to morbidity, mortality, and length of stay. But pulmonary complications are better predictors of long-term mortality after surgery.⁷

There are several well-validated risk factors for increased perioperative pulmonary morbidity and mortality—HF, chronic obstructive pulmonary disease (COPD), advanced age, and the need for assistance with activities of daily living among them. In addition to identifying patient-specific risk factors, knowledge of the type of surgery planned will provide insight into procedure-specific risk factors (TABLE 1). The approach to the surgical pulmonary patient is addressed in an American College of Physicians (ACP) guideline published in 2006 and available at http://www.annals.org/content/144/8/575.full.pdf+html.⁷

What tests to consider? The ACP guideline is notable not only for its recommendations, but for the things that are not recommended but may nevertheless be considered the standard of care in some locales. Chest radiography and spirometry are 2 such examples. Although these tests may be appropriate on an individual basis for patients with a previous diagnosis of COPD or asthma, their routine use is of little value—and the ACP does not recommend them as part of a standard preop evaluation.⁷ Some laboratory tests may aid in risk stratification, however.

A serum albumin level <35 g/L is strongly associated with postop pulmonary complications.⁸ Checking levels in all patients suspected of hypoalbuminemia, including any patient with 1 or more pulmonary risk factors, is reasonable for a physician performing a preoperative evaluation. Consider checking blood urea nitrogen (BUN) levels, as well. Uremia (BUN >21 mg/dL) is also associated with increased pulmonary complications, although not as strongly as hypoalbuminemia.

Postpone or proceed? Acute conditions are another key consideration. An upper respiratory infection (URI) increases the risk of postoperative pulmonary complications, especially in children.^9,10 A simple algorithm offers guidance in deciding when to postpone surgery in pediatric patients with a URI:⁹

Recommend that it be delayed if the procedure involves general anesthesia and 1 or more of the following risk factors is present: asthma, a history of prematurity, copious secretions, a parent who smokes, planned use of an endotracheal tube, or a procedure involving the airway.

Surgery can proceed if symptoms of the infection are mild, general anesthesia is not required, or a risk/benefit analysis supports it. Considerations include the urgency of the procedure, whether the surgery has previously been postponed, the comfort level of the clinicians involved, and the distance the family must travel for the procedure.¹¹

If you recommend that surgery proceed as planned, suggest perioperative interventions to mitigate risk. Recommend that a laryngeal mask airway be used, if needed, in place of an endotracheal tube; that pulse oximetry monitoring occur; that good hydration and humidification of air be provided; and that the patient receive anticholinergic agents for secretions.

Other measures that have been shown to be effective in reducing perioperative pulmonary complications include deep breathing exercises (incentive spirometry) and the use of a nasogastric tube for those with postoperative emesis, intolerance of oral intake, or symptomatic abdominal distension.⁷ If your patient has risk factors for pulmonary complications, include a recommendation for a postop nasogastric tube in your preop consultation note. However, newer data indicating that patients had fewer pulmonary complications, a more rapid return of normal bowel function, no increased discomfort, and no increase in anastomotic leaks without a nasogastric tube^12,13 may lead to guideline revision.

A scoring system helps evaluate renal risk
Patients with CRF face increased risk of perioperative morbidity and mortality. But as long as the glomerular filtration rate (GFR) is >25 mL/min—which is only 25% of normal—surgery is generally well tolerated. As GFR drops to 10 to 15 mL/min, the rate of surgical complications rises rapidly, reaching 55% to 60%. For such patients, preoperative dialysis is worth considering.¹⁴

Postoperative acute kidney injury (AKI), as acute renal failure is now known,¹⁵ is associated with a 58% mortality rate.¹⁶ Fortunately, this complication develops in only about 1% of surgical patients.¹⁷ Both patient-specific risk factors (CRF, with creatinine >2.1 mg/dL; HF; diabetes, particularly being insulin dependent; age >60 years; jaundice) and procedure-specific risks (aortic, cardiovascular, or liver transplant surgery) help predict which surgical candidates face the highest risk.^16,18,19 Thakar et al have developed a scoring system to identify those at greatest risk for AKI.²⁰ (See “Cardiovascular surgery and acute kidney injury: Scoring the risk” at www.jfponline.com by clicking on “Before surgery: Have you done enough to mitigate risk?” and scrolling to the end.)

Minimize renal complications. Helping patients achieve good intravascular volume and osmolar status preoperatively will reduce their risk of renal complications. Other prophylactic measures: Minimize exposure to nephrotoxins (eg, nonsteroidal anti-inflammatory drugs or contrast media) to the extent possible. Consider evaluating the serum electrolyte and creatinine levels of patients with multiple risk factors to determine whether they can safely undergo surgery; some experts suggest preoperative urinalysis, as well.¹⁸

Patients with end-stage renal disease have very high perioperative morbidity.²¹ They are at increased risk for hyperkalemia, infection, hyper- and hypotension, bleeding, arrhythmias, and clotted fistulas, in descending order of incidence.¹⁸ Preoperative planning, including the need for dialysis before surgery, is necessary to manage these risks.

Risk of postop infection: Focusing on the foreseeable
Postoperative infections, both at the surgical site and remote from the incision, are a significant cause of morbidity and mortality. Pneumonia is among the most prominent remote infections associated with surgery,²² and early ambulation, deep breathing exercises, and tight glycemic control can greatly decrease the risk.

Surgical site infection (SSI) remains an important concern, occurring in 37% of cases.²³ Risk factors include hyperglycemia, malnutrition, perioperative steroid use, preexisting infections, tobacco smoking, peripheral vascular disease, advanced age, radiation therapy, blood transfusions, prolonged preoperative stay, preoperative shaving, hypothermia, hypoxia, length of operation, and postoperative incontinence.²⁴ While many of these risk factors are dependent on interventions in the operating room and recovery room or during subsequent hospitalization, it is important to address foreseeable risks as part of the preoperative evaluation.

Glycemic control is crucial. Perhaps the most well-documented risk for SSI is hyperglycemia—a common problem among hospitalized patients.¹⁶ Hyperglycemia impairs leukocyte and complement function,^25,26 thereby increasing risk of infectious complications. Tight glycemic control in the surgical patient, especially on the surgical intensive care unit, has been associated with improved outcomes.²⁷

Identify the presence of diabetes in the preoperative consult note, and adjust the patient’s medication regimen as needed, to help him or her achieve optimal glycemic control. In some cases, it may be necessary to delay nonurgent surgery until the patient achieves adequate control.

Malnutrition is another risk factor for SSI. For patients who are undernourished or morbidly obese, checking serum albumin levels may be beneficial. Supplementation for 1 to 2 weeks prior to surgery may decrease the risk of infection for patients who are undernourished;²⁸ for obese patients, weight loss is beneficial. Although significant preoperative weight loss may not be possible, it is important to list an elevated body mass index as a risk factor in the consultation note.

Corticosteroids, used to treat conditions such as COPD, inflammatory bowel disease, allergies, and autoimmune disorders, are another risk factor for perioperative infection. In addition to their effect on glycemic control, corticosteroids directly suppress the immune system. Whenever possible, they should be discontinued preoperatively. If this is not possible, call attention to the patient’s use of corticosteroids in the consultation note.

Preexisting infection presents the possibility of the spread of organisms to the surgical site and, whenever possible, surgery should be postponed until the infection resolves. If the patient has a history of prior infection or colonization with methicillin-resistant Staphylococcus aureus, be sure to include that in the consultation note, as well.

Leukocyte-containing blood product transfusions are associated with a 2-fold increase in some postop infectious complications.^29-31 This is in addition to the well-known risk of bloodborne pathogens associated with transfusions, and is yet another reason to avoid perioperative transfusions whenever possible.

Smoking impairs tissue oxygenation, which delays healing and increases risk of infection. Smoking cessation should be strongly encouraged at every preoperative consultation. Recommend nicotine replacement therapy even for patients who aren’t willing to quit altogether; point out that giving up cigarettes for just 30 days (or more) before surgery can decrease the likelihood of complications.²⁸

In addition to these identified risk factors, anything that compromises the immune status increases the risk of infection. Alcohol or drug abusers, chronic pain patients, transplant recipients, cancer patients taking immunosuppressants, postsplenectomy patients, and patients with HIV are all at increased risk. Identify any such conditions during your preoperative evaluation, and be sure to include them in your communication with the surgical team.

A common request in preop consults relates to bacterial endocarditis prophylaxis. Only an extremely small number of cases of infective endocarditis occur with dental procedures, however, so the benefits of antibiotic prophylaxis would be minimal, even if the prophylactic therapy were 100% effective.³² As a result, the ACC/AHA guidelines recommend prophylaxis for dental procedures only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis. Administration of antibiotics solely to prevent endocarditis is not recommended for patients undergoing genitourinary or gastrointestinal tract procedures.³²

Hematologic evaluation: Address risks of bleeding, clotting
Historically, a variety of tests have been employed in an effort to identify patients at risk for bleeding complications prior to surgery—including prothrombin time, partial thromboplastin time, platelet count, and bleeding time, or platelet function. While highly reproducible, automated, and inexpensive when considered individually, the cumulative cost of routine use of these tests is high.³³

A recent review of the literature indicates that, for surgical patients without synthetic liver dysfunction or a history of oral anticoagulant use, routine testing is of little value in the assessment of bleeding risk.³⁴ Patients with a negative bleeding history do not require routine coagulation screening prior to surgery.³⁵

Instead, use the medical history to identify risk factors for bleeding. These include excessive bruising, nosebleeds, prolonged bleeding after cuts, bleeding >3 minutes after brushing teeth, and heavy or prolonged menses (TABLE 1). Patients with a past medical history of liver disease; renal failure; hypersplenism; hematologic disease; collagen vascular disease; hemophilia or other inherited hemorrhagic disorder; gastrointestinal or urogenital blood loss; and severe bleeding after dental extraction, other surgery, or childbirth are also at heightened risk, as are those who take medications that affect hemostasis. Physical findings suggestive of risk include purpura, hematoma, jaundice, and signs of cirrhosis.³⁴

While laboratory testing is only appropriate to confirm those at risk in the subpopulation selected by the history and physical, here, as with other adjunctive testing, it is important to consider local standards and the preferences of the surgeon who requested the preop consult.

Treat anemia. Preoperative anemia is linked to adverse outcomes in surgical patients,³⁶ although it is not clear whether the anemia itself or the perioperative transfusions associated with the condition are at the root of the problem.³⁷ Macrocytic anemia may require treatment with vitamin B₁₂ and folate; iron deficiency anemia is treated with iron. Some physicians also recommend the use of erythropoietin starting 3 weeks prior to surgery for patients with normocytic anemia with hemoglobin <13 g/dL.^38,39

Thromboembolism risk. Excessive clotting is responsible for more perioperative complications than excessive bleeding. There is a high prevalence of venous thromboembolism (VTE) among surgical patients, with both patient- and procedure-specific risk factors. Although a variety of coagulopathies increase the baseline risk for VTE, routine laboratory screening of the general surgical population for thrombophilia is not recommended.^34,35

When risk factors are present based on both the patient’s medical history and the type of procedure, prophylactic measures may be needed (TABLE 3). Options include mechanical prophylaxis (graduated compression stockings and intermittent pneumatic devices) and chemoprophylaxis. Recommended for high-risk cases, such as patients undergoing orthopedic surgery that precludes early mobilization, chemoprophylaxis options include low-molecular-weight heparin, low-dose unfractionated heparin, fondaparinux (a synthetic factor Xa inhibitor), and vitamin K antagonists such as warfarin.⁴⁰ Aspirin alone is not recommended, as it has not been found to be an effective prophylaxis for VTE.

CASE After following this system-by-system review of your patient, Charlie H, you identify and explicitly communicate the following risk factors in your consultation note:

• Cardiovascular: type 2 diabetes, low functional capacity
• Pulmonary: advanced age
• Renal: advanced age
• Infectious: type 2 diabetes, advanced age, BMI=39
• Hematologic: advanced age, obesity

Based on these findings, you develop the following plan for Charlie H, detailed in the consultation note you submit to the surgical team:

• Continue home diabetes medications perioperatively, supplemented with a basal-bolus insulin regimen.
• Initiate incentive spirometry postoperatively; use an NG tube if postoperative nausea and vomiting occur.
• Maintain MAP >65 mm Hg.
• Institute aggressive early ambulation and use of graduated compression stockings for DVT prophylaxis.
  Submitted by ___________ on ________.

TABLE 3
Perioperative thromboembolism: Risk and prophylaxis

CORRESPONDENCE Mark K. Huntington, MD, PhD, FAAFP, Center for Family Medicine, 1115 East Twentieth Street, Sioux Falls, SD 57105; [email protected]

CASE Charlie H, an elderly man who has been your patient for more than 10 years, is scheduled for inguinal hernia repair, and has come in for a preoperative evaluation. Based on his medical history and a physical examination, you identify several risk factors for surgical complications: a low functional capacity (<4 METS), obesity (BMI=39), advanced age (70 years), and type 2 diabetes (well controlled). What should you write in your consultation note about Charlie’s perioperative risks, and what interventions should you institute—or recommend—to mitigate his risk?

A preoperative consult, a service that family physicians are well positioned to provide, requires a thorough and systematic approach. But because of time pressures—as well as a dearth of perioperative templates, guidelines, and checklists—a cursory history and physical exam often takes the place of a comprehensive evaluation.

A thorough medical history is the most valuable tool of a physician doing a preop consult, but a comprehensive evaluation also involves the assessment of perioperative risk factors, ancillary tests to consider, and interventions to recommend to mitigate risks. Although various published guidelines address specific systems, there are few places where family physicians can find a complete toolkit. The text and tables that follow, which form the core of a comprehensive resource initially compiled to help our residents conduct clear and effective preoperative consults, will help you safeguard your patients.

A system-by-system review starts with the heart

The vast majority of perioperative problems fall into a handful of categories: cardiac, pulmonary, renal, infectious, and hematologic complications (TABLE 1). When a surgeon requests a preoperative evaluation, however, the patient’s cardiac status is generally the primary concern. This is also the portion of the preop consult with the most formally structured guidelines; those issued by the American College of Cardiology and American Heart Association (ACC/AHA) are the most widely used.¹ Initially based primarily on expert opinion, the ACC/AHA guidelines are increasingly evidence-based (http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.109.192690).^1,2 These guidelines address the evaluation of patients for noncardiac surgery. Both cardiac surgery and emergent operations are beyond the scope of the guidelines, and are not addressed here.

Patients with unstable coronary syndromes—eg, unstable angina or myocardial infarction (MI) within the past 30 days, decompensated heart failure (HF), significant arrhythmias, or severe valvular disease—face an increased risk of perioperative morbidity and mortality. To reduce the risk, such patients require optimization of the underlying condition before undergoing elective surgery.¹

Is additional cardiac testing necessary? Whether you’re assessing for cardiac status or other risks, for that matter, evidence supports the use of ancillary testing in only a small minority of surgical patients. A general rule of thumb—regardless of the system you’re assessing—is to consider adjunctive testing only if the outcome has the potential to alter patient management. Thus, exercise stress testing or resting electrocardiography (EKG), among other tests, may be considered on an individual basis (TABLE 2), but studies have failed to demonstrate improved outcomes with added testing of cardiac status on a routine basis.^5,6

Evidence is insufficient to make a firm recommendation regarding additional cardiac testing, even for patients with more than 3 clinical risk factors. Nonetheless, the ACC/AHA guidelines favor the use of adjunctive testing in such cases, especially for patients who are candidates for high-risk procedures, such as vascular surgery.¹

What’s the local standard of care? Studies to determine when further testing is beneficial and which tests would benefit which patients are ongoing. In the absence of definitive findings, it behooves primary care physicians to familiarize themselves with the practices and preferences of the cardiologists and anesthesiologists at the facility where the surgery will be performed and to follow the local standard of care.

TABLE 1
Identifying—and minimizing—perioperative risk

TABLE 2
When should you order these ancillary tests?*

Identify pulmonary risks with help from ACP
Postoperative pulmonary complications are as prevalent as cardiac complications, and contribute equally to morbidity, mortality, and length of stay. But pulmonary complications are better predictors of long-term mortality after surgery.⁷

There are several well-validated risk factors for increased perioperative pulmonary morbidity and mortality—HF, chronic obstructive pulmonary disease (COPD), advanced age, and the need for assistance with activities of daily living among them. In addition to identifying patient-specific risk factors, knowledge of the type of surgery planned will provide insight into procedure-specific risk factors (TABLE 1). The approach to the surgical pulmonary patient is addressed in an American College of Physicians (ACP) guideline published in 2006 and available at http://www.annals.org/content/144/8/575.full.pdf+html.⁷

What tests to consider? The ACP guideline is notable not only for its recommendations, but for the things that are not recommended but may nevertheless be considered the standard of care in some locales. Chest radiography and spirometry are 2 such examples. Although these tests may be appropriate on an individual basis for patients with a previous diagnosis of COPD or asthma, their routine use is of little value—and the ACP does not recommend them as part of a standard preop evaluation.⁷ Some laboratory tests may aid in risk stratification, however.

A serum albumin level <35 g/L is strongly associated with postop pulmonary complications.⁸ Checking levels in all patients suspected of hypoalbuminemia, including any patient with 1 or more pulmonary risk factors, is reasonable for a physician performing a preoperative evaluation. Consider checking blood urea nitrogen (BUN) levels, as well. Uremia (BUN >21 mg/dL) is also associated with increased pulmonary complications, although not as strongly as hypoalbuminemia.

Postpone or proceed? Acute conditions are another key consideration. An upper respiratory infection (URI) increases the risk of postoperative pulmonary complications, especially in children.^9,10 A simple algorithm offers guidance in deciding when to postpone surgery in pediatric patients with a URI:⁹

Recommend that it be delayed if the procedure involves general anesthesia and 1 or more of the following risk factors is present: asthma, a history of prematurity, copious secretions, a parent who smokes, planned use of an endotracheal tube, or a procedure involving the airway.

Surgery can proceed if symptoms of the infection are mild, general anesthesia is not required, or a risk/benefit analysis supports it. Considerations include the urgency of the procedure, whether the surgery has previously been postponed, the comfort level of the clinicians involved, and the distance the family must travel for the procedure.¹¹

If you recommend that surgery proceed as planned, suggest perioperative interventions to mitigate risk. Recommend that a laryngeal mask airway be used, if needed, in place of an endotracheal tube; that pulse oximetry monitoring occur; that good hydration and humidification of air be provided; and that the patient receive anticholinergic agents for secretions.

Other measures that have been shown to be effective in reducing perioperative pulmonary complications include deep breathing exercises (incentive spirometry) and the use of a nasogastric tube for those with postoperative emesis, intolerance of oral intake, or symptomatic abdominal distension.⁷ If your patient has risk factors for pulmonary complications, include a recommendation for a postop nasogastric tube in your preop consultation note. However, newer data indicating that patients had fewer pulmonary complications, a more rapid return of normal bowel function, no increased discomfort, and no increase in anastomotic leaks without a nasogastric tube^12,13 may lead to guideline revision.

A scoring system helps evaluate renal risk
Patients with CRF face increased risk of perioperative morbidity and mortality. But as long as the glomerular filtration rate (GFR) is >25 mL/min—which is only 25% of normal—surgery is generally well tolerated. As GFR drops to 10 to 15 mL/min, the rate of surgical complications rises rapidly, reaching 55% to 60%. For such patients, preoperative dialysis is worth considering.¹⁴

Postoperative acute kidney injury (AKI), as acute renal failure is now known,¹⁵ is associated with a 58% mortality rate.¹⁶ Fortunately, this complication develops in only about 1% of surgical patients.¹⁷ Both patient-specific risk factors (CRF, with creatinine >2.1 mg/dL; HF; diabetes, particularly being insulin dependent; age >60 years; jaundice) and procedure-specific risks (aortic, cardiovascular, or liver transplant surgery) help predict which surgical candidates face the highest risk.^16,18,19 Thakar et al have developed a scoring system to identify those at greatest risk for AKI.²⁰ (See “Cardiovascular surgery and acute kidney injury: Scoring the risk” at www.jfponline.com by clicking on “Before surgery: Have you done enough to mitigate risk?” and scrolling to the end.)

Minimize renal complications. Helping patients achieve good intravascular volume and osmolar status preoperatively will reduce their risk of renal complications. Other prophylactic measures: Minimize exposure to nephrotoxins (eg, nonsteroidal anti-inflammatory drugs or contrast media) to the extent possible. Consider evaluating the serum electrolyte and creatinine levels of patients with multiple risk factors to determine whether they can safely undergo surgery; some experts suggest preoperative urinalysis, as well.¹⁸

Patients with end-stage renal disease have very high perioperative morbidity.²¹ They are at increased risk for hyperkalemia, infection, hyper- and hypotension, bleeding, arrhythmias, and clotted fistulas, in descending order of incidence.¹⁸ Preoperative planning, including the need for dialysis before surgery, is necessary to manage these risks.

Risk of postop infection: Focusing on the foreseeable
Postoperative infections, both at the surgical site and remote from the incision, are a significant cause of morbidity and mortality. Pneumonia is among the most prominent remote infections associated with surgery,²² and early ambulation, deep breathing exercises, and tight glycemic control can greatly decrease the risk.

Surgical site infection (SSI) remains an important concern, occurring in 37% of cases.²³ Risk factors include hyperglycemia, malnutrition, perioperative steroid use, preexisting infections, tobacco smoking, peripheral vascular disease, advanced age, radiation therapy, blood transfusions, prolonged preoperative stay, preoperative shaving, hypothermia, hypoxia, length of operation, and postoperative incontinence.²⁴ While many of these risk factors are dependent on interventions in the operating room and recovery room or during subsequent hospitalization, it is important to address foreseeable risks as part of the preoperative evaluation.

Glycemic control is crucial. Perhaps the most well-documented risk for SSI is hyperglycemia—a common problem among hospitalized patients.¹⁶ Hyperglycemia impairs leukocyte and complement function,^25,26 thereby increasing risk of infectious complications. Tight glycemic control in the surgical patient, especially on the surgical intensive care unit, has been associated with improved outcomes.²⁷

Identify the presence of diabetes in the preoperative consult note, and adjust the patient’s medication regimen as needed, to help him or her achieve optimal glycemic control. In some cases, it may be necessary to delay nonurgent surgery until the patient achieves adequate control.

Malnutrition is another risk factor for SSI. For patients who are undernourished or morbidly obese, checking serum albumin levels may be beneficial. Supplementation for 1 to 2 weeks prior to surgery may decrease the risk of infection for patients who are undernourished;²⁸ for obese patients, weight loss is beneficial. Although significant preoperative weight loss may not be possible, it is important to list an elevated body mass index as a risk factor in the consultation note.

Corticosteroids, used to treat conditions such as COPD, inflammatory bowel disease, allergies, and autoimmune disorders, are another risk factor for perioperative infection. In addition to their effect on glycemic control, corticosteroids directly suppress the immune system. Whenever possible, they should be discontinued preoperatively. If this is not possible, call attention to the patient’s use of corticosteroids in the consultation note.

Preexisting infection presents the possibility of the spread of organisms to the surgical site and, whenever possible, surgery should be postponed until the infection resolves. If the patient has a history of prior infection or colonization with methicillin-resistant Staphylococcus aureus, be sure to include that in the consultation note, as well.

Leukocyte-containing blood product transfusions are associated with a 2-fold increase in some postop infectious complications.^29-31 This is in addition to the well-known risk of bloodborne pathogens associated with transfusions, and is yet another reason to avoid perioperative transfusions whenever possible.

Smoking impairs tissue oxygenation, which delays healing and increases risk of infection. Smoking cessation should be strongly encouraged at every preoperative consultation. Recommend nicotine replacement therapy even for patients who aren’t willing to quit altogether; point out that giving up cigarettes for just 30 days (or more) before surgery can decrease the likelihood of complications.²⁸

In addition to these identified risk factors, anything that compromises the immune status increases the risk of infection. Alcohol or drug abusers, chronic pain patients, transplant recipients, cancer patients taking immunosuppressants, postsplenectomy patients, and patients with HIV are all at increased risk. Identify any such conditions during your preoperative evaluation, and be sure to include them in your communication with the surgical team.

A common request in preop consults relates to bacterial endocarditis prophylaxis. Only an extremely small number of cases of infective endocarditis occur with dental procedures, however, so the benefits of antibiotic prophylaxis would be minimal, even if the prophylactic therapy were 100% effective.³² As a result, the ACC/AHA guidelines recommend prophylaxis for dental procedures only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis. Administration of antibiotics solely to prevent endocarditis is not recommended for patients undergoing genitourinary or gastrointestinal tract procedures.³²

Hematologic evaluation: Address risks of bleeding, clotting
Historically, a variety of tests have been employed in an effort to identify patients at risk for bleeding complications prior to surgery—including prothrombin time, partial thromboplastin time, platelet count, and bleeding time, or platelet function. While highly reproducible, automated, and inexpensive when considered individually, the cumulative cost of routine use of these tests is high.³³

A recent review of the literature indicates that, for surgical patients without synthetic liver dysfunction or a history of oral anticoagulant use, routine testing is of little value in the assessment of bleeding risk.³⁴ Patients with a negative bleeding history do not require routine coagulation screening prior to surgery.³⁵

Instead, use the medical history to identify risk factors for bleeding. These include excessive bruising, nosebleeds, prolonged bleeding after cuts, bleeding >3 minutes after brushing teeth, and heavy or prolonged menses (TABLE 1). Patients with a past medical history of liver disease; renal failure; hypersplenism; hematologic disease; collagen vascular disease; hemophilia or other inherited hemorrhagic disorder; gastrointestinal or urogenital blood loss; and severe bleeding after dental extraction, other surgery, or childbirth are also at heightened risk, as are those who take medications that affect hemostasis. Physical findings suggestive of risk include purpura, hematoma, jaundice, and signs of cirrhosis.³⁴

While laboratory testing is only appropriate to confirm those at risk in the subpopulation selected by the history and physical, here, as with other adjunctive testing, it is important to consider local standards and the preferences of the surgeon who requested the preop consult.

Treat anemia. Preoperative anemia is linked to adverse outcomes in surgical patients,³⁶ although it is not clear whether the anemia itself or the perioperative transfusions associated with the condition are at the root of the problem.³⁷ Macrocytic anemia may require treatment with vitamin B₁₂ and folate; iron deficiency anemia is treated with iron. Some physicians also recommend the use of erythropoietin starting 3 weeks prior to surgery for patients with normocytic anemia with hemoglobin <13 g/dL.^38,39

Thromboembolism risk. Excessive clotting is responsible for more perioperative complications than excessive bleeding. There is a high prevalence of venous thromboembolism (VTE) among surgical patients, with both patient- and procedure-specific risk factors. Although a variety of coagulopathies increase the baseline risk for VTE, routine laboratory screening of the general surgical population for thrombophilia is not recommended.^34,35

When risk factors are present based on both the patient’s medical history and the type of procedure, prophylactic measures may be needed (TABLE 3). Options include mechanical prophylaxis (graduated compression stockings and intermittent pneumatic devices) and chemoprophylaxis. Recommended for high-risk cases, such as patients undergoing orthopedic surgery that precludes early mobilization, chemoprophylaxis options include low-molecular-weight heparin, low-dose unfractionated heparin, fondaparinux (a synthetic factor Xa inhibitor), and vitamin K antagonists such as warfarin.⁴⁰ Aspirin alone is not recommended, as it has not been found to be an effective prophylaxis for VTE.

CASE After following this system-by-system review of your patient, Charlie H, you identify and explicitly communicate the following risk factors in your consultation note:

• Cardiovascular: type 2 diabetes, low functional capacity
• Pulmonary: advanced age
• Renal: advanced age
• Infectious: type 2 diabetes, advanced age, BMI=39
• Hematologic: advanced age, obesity

Based on these findings, you develop the following plan for Charlie H, detailed in the consultation note you submit to the surgical team:

• Continue home diabetes medications perioperatively, supplemented with a basal-bolus insulin regimen.
• Initiate incentive spirometry postoperatively; use an NG tube if postoperative nausea and vomiting occur.
• Maintain MAP >65 mm Hg.
• Institute aggressive early ambulation and use of graduated compression stockings for DVT prophylaxis.
  Submitted by ___________ on ________.

TABLE 3
Perioperative thromboembolism: Risk and prophylaxis

CORRESPONDENCE Mark K. Huntington, MD, PhD, FAAFP, Center for Family Medicine, 1115 East Twentieth Street, Sioux Falls, SD 57105; [email protected]

A 13-month-old girl arrives at your clinic, referred by the staff at the Women, Infants, and Children (WIC) nutritional center where her parents—recent immigrants from Africa—go for food supplements. The baby is bundled up in layers of clothing, even though it’s a relatively mild winter day. The father carries her into the examining room and undresses her. The child is tiny and dark-skinned, with curly hair painstakingly divided into little bunches. The parents seem caring, loving, and not particularly worried. They tell you the nurse at the WIC center thought their baby was not gaining enough weight and advised them to bring the baby to you. The referral note from WIC says hemoglobin levels found on routine blood test were low. You list the presenting complaint as anemia.

Q: What are some of the etiologies for anemia in a child this age? What strategies would you use to narrow down the cause?

Additional medical history

• The birth history is unremarkable, with neither antepartum nor postpartum complications.
• At her 6-month well-child checkup, neither the child’s physician nor her parents expressed any concerns about her development. Her parents received the routine anticipatory guidance at that visit, including advice on breastfeeding, vitamin supplementation, vaccination, and care of minor illnesses.
• She hasn’t been in for a well-child visit since then, but she has been seen for an upper respiratory infection and a bout of gastroenteritis. Her parents have not been worried about her health.
• The parents tell you the baby doesn’t sleep soundly, scratches her skin in her sleep, and cries a lot.

Family and social history

• The parents speak very little English.
• The patient is an only child, and no extended family live in the area.
• Her mother works nights and her father works days, with the parent who is not working caring for her at home.
• Her parents tell you she takes small sips of juice or water, and an occasional bite of noodles. She won’t drink milk at all and refuses any other foods they offer.

Physical examination

• The child is in no acute distress. She is afebrile, and her vital signs are appropriate for her age.
• Height is 27½ inches, weight 15 lb, 15 oz, placing her at less than the 5th percentile for height and weight for her age—a regression from the 50th percentile she showed at earlier visits.
• Head and neck exam reveals mild frontal bossing and prominent sternoclavicular joints. There is no adenopathy or thyromegaly.
• Heart and lung exam are normal.
• Abdomen is soft, nontender, nondistended, with bowel sounds present.
• There is slight bowing of the lower extremities and puffiness around the wrists and ankles. When you ask her father to have her stand on the examining table, you see that she needs support to do so (FIGURE 1).

Q: What is your clinical diagnosis, and what tests will you order?

FIGURE 1
The patient, not weight-bearing

Laboratory results

• Hemoglobin, 9.9 mg/dL
  (normal: 10.4-12.4 mg/dL)
• Mean corpuscular volume (MCV), 74 fL
  (normal: 70-86 fL)
• Alkaline phosphatase, 3417 U/L
  (normal: 115-460 U/L)
• Vitamin D (calcidiol), <7 nmol/L
  (normal: 60-108 nmol/L)
• Calcium, 9.1 mg/dL
  (normal: 8.8-10.8 mg/dL)
• Comprehensive metabolic panel, liver transaminases, and thyroid-stimulating hormone levels are all normal
• Parathyroid hormone level, 101 pg/mL
  (normal: 10-55 pg/mL).

Radiologic findings

• X-ray shows slight saber deformity of the femurs and broadening of the epiphyses of the forearm (FIGURE 2).

FIGURE 2
Forearm x-ray

Can this be rickets?

Here is a child with a history of poor growth and peculiar eating habits. Her legs are bowed and her wrists seem swollen. She does not stand or walk, and refuses to bear weight on her legs. She is anemic, and the lab tests you’ve ordered show abnormal vitamin D, alkaline phosphatase, and parathyroid hormone levels. All of this suggests a diagnosis of rickets.

Causes of rickets

Rickets is the result of abnormal mineralization of bone and cartilage in growing children. The analogous condition in adults whose epiphyseal plates have closed is osteomalacia. Clinical rickets typically presents with the constellation of signs and symptoms listed in the box and depicted in FIGURES 1, 2, and 3.

FIGURE 3
Rachitic rosary

Not enough vitamin D

The most common cause of rickets is a deficiency of vitamin D, a substance physiologically necessary to produce concentrations of calcium and phosphate adequate for proper bone mineralization. Vitamin D is produced in the skin in the presence of sunlight and can also be ingested in supplements and certain foods.

Vitamin D deficiency may result from reduced sunlight exposure, inadequate dietary intake, malabsorption, or a combination of these factors.¹ Rickets may also be caused by medications that alter absorption or secretion of phosphate and calcium, including antacids, anticonvulsants, corticosteroids, and loop diuretics. Various disease states, such as Crohn’s disease, pancreatic disease, biliary disease, gastrointestinal loops and fistulae, cirrhosis, chronic renal disease, and mesenchymal tumors, may also alter absorption and metabolism of these ions.

How much sunshine does a baby need?

It doesn’t take a great deal of sunlight exposure to provide adequate supplies of vitamin D. An infant wearing only a diaper will get enough vitamin D from half an hour per week of sun exposure. A fully clothed infant needs 3 hours. But children with dark skin, like this African baby, need more time in the sun. And if parents follow current anticipatory guidance about protecting children from overexposure to the sun and slather on the sunscreen, vitamin D synthesis decreases by more than 95%.²

Vitamin D in the diet

Consuming adequate quantities of vitamin D is difficult, unless the diet includes fortified foods or vitamin supplements. Current recommendations for daily intake are 400 IU per day for all infants, children, and adolescents.³ But the average daily intake by adults in North America from sources such as fish, eggs, and butter or margarine is only 50 to 100 IU.³

Infants born to vitamin-D replete women have an 8- to 12-week store of vitamin D at birth, but breastfeeding does not ensure the baby is getting adequate amounts of vitamin D, even if the mother’s vitamin D status is adequate. Human milk from vitamin D-replete women has a vitamin D concentration of only 25 IU per liter, far below the recommended daily intake of 400 IU.³

How deficient is this baby?

Vitamin D deficiency may be categorized as mild, moderate, or severe. Calcidiol is the next-to-last step in the metabolism of vitamin D and is used as a marker because it is easier to measure than the concentration of calcitriol, the final step. Mild vitamin D deficiency is defined as serum calcidiol concentration of 25 to 50 nmol/L. A serum calcidiol concentration of 12.5 to 25 nmol/L indicates a moderate vitamin D deficiency, and at those levels the incidence of hypocalcemia and rickets increases. Serum calcidiol concentration of less than 12.5 nmol/L, as in the case of the patient presented here, indicates a severe deficiency.⁴

Not enough calcium

In addition to calcium malabsorption due to inadequate vitamin D levels, hypocalcemia may result from inadequate intake of calcium or from vitamin D-dependent metabolic disorders, of which there are 2 types.

Type I, sometimes known as pseudo-vitamin D-deficiency rickets, is due to defective production of 25(OH)D₃-1-α-hydroxylase, an enzyme necessary for the conversion of calcidiol to calcitriol in the kidneys.

Type II, also called hereditary rickets, is rare. It is caused by mutations in vitamin D receptors and the inability of the ligand to bind or stimulate the proper physiologic response. In this condition, laboratory tests may show high levels of calcitriol.

Not enough phosphorus

Vitamin D-resistant rickets, or familial hypophosphatemic rickets, refers to a clinical presentation of rickets that is caused by a hereditary renal wasting of phosphorus at the proximal tubule level. Laboratory evaluation of a child with this condition will show low phosphate levels, normal calcitriol levels, and hypercalciuria. The specific defect that causes this condition is not known. A family history of short stature, orthopedic abnormalities, poor dentition, alopecia, or parental consanguinity may be suggestive of vitamin D-dependent or vitamin D-resistant forms of inherited rickets.

Other causes of hypophosphatemia include inadequate nutritional intake, X-linked hypophosphatemia, generalized tubular disorders such as renal tubular acidosis, Fanconi syndrome, and Dent disease. These disorders may also lead to rickets.

Q: What are the available treatments for rickets? What about prevention?

Replenishing vitamin D

Vitamin D deficiency may be remedied by supplementing anywhere along the metabolic pathway. Dihydrotachysterol (DHT, or D₁), the substance in the skin that responds to sunlight, is given as 60,000 IU once, then 6000 IU daily until the rickets are clinically and radiologically resolved. Further downstream, ergocalciferol (D₂) may be given as 1000 to 5000 IU daily for 6 to 12 weeks. The dosage is calibrated by age: 1000 IU/d if age <1 month, 3000 IU/d for ages 1 to 12 months, and 5000 IU/d for children older than 12 months. The final form of vitamin D is cholecalciferol (D₃). This is typically administered as either 5000 to 10,000 IU daily for 2 to 3 months, or as 600,000 IU in 1 day, divided into 4 to 6 doses.^5,6 All of these supplements taste bad and children are often resistant to swallowing them.

When follow-up and multiple dosing are impractical—because the family finds repeated clinic visits too difficult, or because the child will not comply with the regimen—you can use stosstherapy.⁷ This is a bolus of cholecalciferol (D₃) or ergocalciferol (D₂), 150,000 to 600,000 IU, given as a single dose or divided over several days. For example, you would give 300,000 IU over 1 to 7 days in children 1 to 12 months of age. With this therapy, onset of action is less than a day and maximal effects are seen in 4 weeks. Some preparations contain propylene glycol, which is limited in food additives to <25 mg/kg of body weight because of potential toxicity.

When supplementation doesn’t work. Vitamin D is not effective in treatment of familial hypophosphatemic rickets, Type II vitamin D-dependent rickets, or disorders of phosphate metabolism.

Monitoring therapeutic success

When possible, treatment should be monitored by checking serum calcium and alkaline phosphatase at 1 month, and calcium, magnesium, phosphate, alkaline phosphatase, calcidiol, parathyroid hormone, and wrist x-ray at 3 months from initiation of treatment, to ensure that they are normalizing.

Preventing rickets

In the developed world, public health efforts to prevent rickets have been largely successful. Rickets was prevalent worldwide in the early decades of the 20th century, but after milk began to be routinely fortified with vitamin D in the 1920s, cases of nutritional rickets almost disappeared in industrialized nations.

In 1963, the American Academy of Pediatrics (AAP) began recommending vitamin D supplementation to prevent rickets. Although the recommendation remains controversial because of concerns about the possibility of hypervitaminosis and the resultant hypercalcemia and hypercalciuria, there has been renewed emphasis on this recommendation in light of a rise in the number of cases of rickets in the United States in recent years.^8-14 Current AAP recommendations for vitamin D supplementation are daily supplementation of 400 IU vitamin D for the following groups:³

• Breastfed infants, beginning with the first few days of life and continued until they are weaned to at least 1000 mL per day of vitamin D-fortified formula or milk.
• Nonbreastfed infants who are ingesting less than 1000 mL per day of vitamin D-fortified formula or milk. Most commercial baby formulas contain 400 IU/L, which means that an intake of 500 mL of formula per day provides 200 IU.¹⁵ Additionally, special milk supplemented with vitamin D₃ up to 200 IU per 250 mL has recently become available in Europe.¹⁶
• Children and adolescents who do not get regular sunlight exposure, do not ingest at least 32 ounces per day of vitamin D-fortified milk, or do not take a daily multivitamin supplement containing at least 400 IU of vitamin D.

Others have suggested a bolus dosing 150,000 IU each autumn for those in northern climates.¹⁷

Most over-the-counter vitamin formulations now contain D₃ (cholecalciferol), as recent studies show this form is more potent than D₂ (ergocalciferol).¹⁸ Calcium supplements are available in combination with vitamin D. Calcitriol, the most active form of vitamin D, is available only by prescription. Because it does not require activation in the kidneys, it is the drug of choice for renally impaired patients.

Q: How would you treat this child?

Bad taste is a big hurdle

The child in this case was prescribed 150,000 U oral cholecalciferol. She spit it out at the clinic, and the dose was sent home for her parents to administer. She was also started on a multivitamin (Poly-Vi-Sol). On the return visit a few days later, the parents reported that she only took three-quarters of the vitamin D dose, spitting out the remainder.

When that didn’t work…

The child was then admitted to the hospital for administration of vitamin D and to allow for dietary and social work evaluations of factors contributing to her malnutrition.

Social services evaluation ruled out an economic etiology for the child’s failure to thrive. The family was able to afford a nutritionally adequate diet for the child. They were enrolled in Medicaid and WIC. Willful neglect was not an issue: A very loving and appropriate relationship was evident between the child and her parents. Child care was shared equally by the young parents, but they simply didn’t know what foods were appropriate for a child of her age.

Turning things around

The hospital dietician observed one of the child’s meals. The child ate some of everything on the plate: mashed potatoes and gravy, chicken strips, vegetables, bananas, yogurt, and milk. She was willing to try a variety of foods, and ate most of them. Both the physician and the dietician spent a lot of time with the parents reviewing feeding techniques and healthy food choices. Language was a problem, solved for the most part with the assistance of a dial-up language translation service to ensure clear understanding of the instructions. The health care professionals prepared a list of healthy foods to buy at the grocery store, with pictures illustrating healthy food items. In addition, appropriate exposure to sunlight was explained and encouraged.

Parent education is the key

The child’s father expressed gratitude several times for the instruction on healthy food choices for the daughter, while the mother smiled in shy agreement. He said they did not know what to feed her, and when she refused most things they offered, they fed her the noodles and juice she seemed to prefer. He was grateful to the nutritionist, social worker, nursing staff, and physicians for taking care of his daughter. He was eager to go to the grocery store and to start feeding her the “right foods.”

Ready to go home

By discharge, the child had received the full dose of vitamin D and was eating a variety of foods, including 1 to 4 ounces of milk daily, supplemented with Poly-Vi-Sol, 1 mL orally twice daily, and calcium carbonate (OsCal) with vitamin D, 1 crushed tablet orally twice daily. Home health nursing provided follow-up twice a week, and weekly appointments in the clinic with the physician were also scheduled. Compliance with the discharge plan was impeccable. Both laboratory and clinical signs of rickets resolved over the subsequent weeks.

A 13-month-old girl arrives at your clinic, referred by the staff at the Women, Infants, and Children (WIC) nutritional center where her parents—recent immigrants from Africa—go for food supplements. The baby is bundled up in layers of clothing, even though it’s a relatively mild winter day. The father carries her into the examining room and undresses her. The child is tiny and dark-skinned, with curly hair painstakingly divided into little bunches. The parents seem caring, loving, and not particularly worried. They tell you the nurse at the WIC center thought their baby was not gaining enough weight and advised them to bring the baby to you. The referral note from WIC says hemoglobin levels found on routine blood test were low. You list the presenting complaint as anemia.

Q: What are some of the etiologies for anemia in a child this age? What strategies would you use to narrow down the cause?

Additional medical history

• The birth history is unremarkable, with neither antepartum nor postpartum complications.
• At her 6-month well-child checkup, neither the child’s physician nor her parents expressed any concerns about her development. Her parents received the routine anticipatory guidance at that visit, including advice on breastfeeding, vitamin supplementation, vaccination, and care of minor illnesses.
• She hasn’t been in for a well-child visit since then, but she has been seen for an upper respiratory infection and a bout of gastroenteritis. Her parents have not been worried about her health.
• The parents tell you the baby doesn’t sleep soundly, scratches her skin in her sleep, and cries a lot.

Family and social history

• The parents speak very little English.
• The patient is an only child, and no extended family live in the area.
• Her mother works nights and her father works days, with the parent who is not working caring for her at home.
• Her parents tell you she takes small sips of juice or water, and an occasional bite of noodles. She won’t drink milk at all and refuses any other foods they offer.

Physical examination

• The child is in no acute distress. She is afebrile, and her vital signs are appropriate for her age.
• Height is 27½ inches, weight 15 lb, 15 oz, placing her at less than the 5th percentile for height and weight for her age—a regression from the 50th percentile she showed at earlier visits.
• Head and neck exam reveals mild frontal bossing and prominent sternoclavicular joints. There is no adenopathy or thyromegaly.
• Heart and lung exam are normal.
• Abdomen is soft, nontender, nondistended, with bowel sounds present.
• There is slight bowing of the lower extremities and puffiness around the wrists and ankles. When you ask her father to have her stand on the examining table, you see that she needs support to do so (FIGURE 1).

Q: What is your clinical diagnosis, and what tests will you order?

FIGURE 1
The patient, not weight-bearing

Laboratory results

• Hemoglobin, 9.9 mg/dL
  (normal: 10.4-12.4 mg/dL)
• Mean corpuscular volume (MCV), 74 fL
  (normal: 70-86 fL)
• Alkaline phosphatase, 3417 U/L
  (normal: 115-460 U/L)
• Vitamin D (calcidiol), <7 nmol/L
  (normal: 60-108 nmol/L)
• Calcium, 9.1 mg/dL
  (normal: 8.8-10.8 mg/dL)
• Comprehensive metabolic panel, liver transaminases, and thyroid-stimulating hormone levels are all normal
• Parathyroid hormone level, 101 pg/mL
  (normal: 10-55 pg/mL).

Radiologic findings

• X-ray shows slight saber deformity of the femurs and broadening of the epiphyses of the forearm (FIGURE 2).

FIGURE 2
Forearm x-ray

Can this be rickets?

Here is a child with a history of poor growth and peculiar eating habits. Her legs are bowed and her wrists seem swollen. She does not stand or walk, and refuses to bear weight on her legs. She is anemic, and the lab tests you’ve ordered show abnormal vitamin D, alkaline phosphatase, and parathyroid hormone levels. All of this suggests a diagnosis of rickets.

Causes of rickets

Rickets is the result of abnormal mineralization of bone and cartilage in growing children. The analogous condition in adults whose epiphyseal plates have closed is osteomalacia. Clinical rickets typically presents with the constellation of signs and symptoms listed in the box and depicted in FIGURES 1, 2, and 3.

FIGURE 3
Rachitic rosary

Not enough vitamin D

The most common cause of rickets is a deficiency of vitamin D, a substance physiologically necessary to produce concentrations of calcium and phosphate adequate for proper bone mineralization. Vitamin D is produced in the skin in the presence of sunlight and can also be ingested in supplements and certain foods.

Vitamin D deficiency may result from reduced sunlight exposure, inadequate dietary intake, malabsorption, or a combination of these factors.¹ Rickets may also be caused by medications that alter absorption or secretion of phosphate and calcium, including antacids, anticonvulsants, corticosteroids, and loop diuretics. Various disease states, such as Crohn’s disease, pancreatic disease, biliary disease, gastrointestinal loops and fistulae, cirrhosis, chronic renal disease, and mesenchymal tumors, may also alter absorption and metabolism of these ions.

How much sunshine does a baby need?

It doesn’t take a great deal of sunlight exposure to provide adequate supplies of vitamin D. An infant wearing only a diaper will get enough vitamin D from half an hour per week of sun exposure. A fully clothed infant needs 3 hours. But children with dark skin, like this African baby, need more time in the sun. And if parents follow current anticipatory guidance about protecting children from overexposure to the sun and slather on the sunscreen, vitamin D synthesis decreases by more than 95%.²

Vitamin D in the diet

Consuming adequate quantities of vitamin D is difficult, unless the diet includes fortified foods or vitamin supplements. Current recommendations for daily intake are 400 IU per day for all infants, children, and adolescents.³ But the average daily intake by adults in North America from sources such as fish, eggs, and butter or margarine is only 50 to 100 IU.³

Infants born to vitamin-D replete women have an 8- to 12-week store of vitamin D at birth, but breastfeeding does not ensure the baby is getting adequate amounts of vitamin D, even if the mother’s vitamin D status is adequate. Human milk from vitamin D-replete women has a vitamin D concentration of only 25 IU per liter, far below the recommended daily intake of 400 IU.³

How deficient is this baby?

Vitamin D deficiency may be categorized as mild, moderate, or severe. Calcidiol is the next-to-last step in the metabolism of vitamin D and is used as a marker because it is easier to measure than the concentration of calcitriol, the final step. Mild vitamin D deficiency is defined as serum calcidiol concentration of 25 to 50 nmol/L. A serum calcidiol concentration of 12.5 to 25 nmol/L indicates a moderate vitamin D deficiency, and at those levels the incidence of hypocalcemia and rickets increases. Serum calcidiol concentration of less than 12.5 nmol/L, as in the case of the patient presented here, indicates a severe deficiency.⁴

Not enough calcium

In addition to calcium malabsorption due to inadequate vitamin D levels, hypocalcemia may result from inadequate intake of calcium or from vitamin D-dependent metabolic disorders, of which there are 2 types.

Type I, sometimes known as pseudo-vitamin D-deficiency rickets, is due to defective production of 25(OH)D₃-1-α-hydroxylase, an enzyme necessary for the conversion of calcidiol to calcitriol in the kidneys.

Type II, also called hereditary rickets, is rare. It is caused by mutations in vitamin D receptors and the inability of the ligand to bind or stimulate the proper physiologic response. In this condition, laboratory tests may show high levels of calcitriol.

Not enough phosphorus

Vitamin D-resistant rickets, or familial hypophosphatemic rickets, refers to a clinical presentation of rickets that is caused by a hereditary renal wasting of phosphorus at the proximal tubule level. Laboratory evaluation of a child with this condition will show low phosphate levels, normal calcitriol levels, and hypercalciuria. The specific defect that causes this condition is not known. A family history of short stature, orthopedic abnormalities, poor dentition, alopecia, or parental consanguinity may be suggestive of vitamin D-dependent or vitamin D-resistant forms of inherited rickets.

Other causes of hypophosphatemia include inadequate nutritional intake, X-linked hypophosphatemia, generalized tubular disorders such as renal tubular acidosis, Fanconi syndrome, and Dent disease. These disorders may also lead to rickets.

Q: What are the available treatments for rickets? What about prevention?

Replenishing vitamin D

Vitamin D deficiency may be remedied by supplementing anywhere along the metabolic pathway. Dihydrotachysterol (DHT, or D₁), the substance in the skin that responds to sunlight, is given as 60,000 IU once, then 6000 IU daily until the rickets are clinically and radiologically resolved. Further downstream, ergocalciferol (D₂) may be given as 1000 to 5000 IU daily for 6 to 12 weeks. The dosage is calibrated by age: 1000 IU/d if age <1 month, 3000 IU/d for ages 1 to 12 months, and 5000 IU/d for children older than 12 months. The final form of vitamin D is cholecalciferol (D₃). This is typically administered as either 5000 to 10,000 IU daily for 2 to 3 months, or as 600,000 IU in 1 day, divided into 4 to 6 doses.^5,6 All of these supplements taste bad and children are often resistant to swallowing them.

When follow-up and multiple dosing are impractical—because the family finds repeated clinic visits too difficult, or because the child will not comply with the regimen—you can use stosstherapy.⁷ This is a bolus of cholecalciferol (D₃) or ergocalciferol (D₂), 150,000 to 600,000 IU, given as a single dose or divided over several days. For example, you would give 300,000 IU over 1 to 7 days in children 1 to 12 months of age. With this therapy, onset of action is less than a day and maximal effects are seen in 4 weeks. Some preparations contain propylene glycol, which is limited in food additives to <25 mg/kg of body weight because of potential toxicity.

When supplementation doesn’t work. Vitamin D is not effective in treatment of familial hypophosphatemic rickets, Type II vitamin D-dependent rickets, or disorders of phosphate metabolism.

Monitoring therapeutic success

When possible, treatment should be monitored by checking serum calcium and alkaline phosphatase at 1 month, and calcium, magnesium, phosphate, alkaline phosphatase, calcidiol, parathyroid hormone, and wrist x-ray at 3 months from initiation of treatment, to ensure that they are normalizing.

Preventing rickets

In the developed world, public health efforts to prevent rickets have been largely successful. Rickets was prevalent worldwide in the early decades of the 20th century, but after milk began to be routinely fortified with vitamin D in the 1920s, cases of nutritional rickets almost disappeared in industrialized nations.

In 1963, the American Academy of Pediatrics (AAP) began recommending vitamin D supplementation to prevent rickets. Although the recommendation remains controversial because of concerns about the possibility of hypervitaminosis and the resultant hypercalcemia and hypercalciuria, there has been renewed emphasis on this recommendation in light of a rise in the number of cases of rickets in the United States in recent years.^8-14 Current AAP recommendations for vitamin D supplementation are daily supplementation of 400 IU vitamin D for the following groups:³

• Breastfed infants, beginning with the first few days of life and continued until they are weaned to at least 1000 mL per day of vitamin D-fortified formula or milk.
• Nonbreastfed infants who are ingesting less than 1000 mL per day of vitamin D-fortified formula or milk. Most commercial baby formulas contain 400 IU/L, which means that an intake of 500 mL of formula per day provides 200 IU.¹⁵ Additionally, special milk supplemented with vitamin D₃ up to 200 IU per 250 mL has recently become available in Europe.¹⁶
• Children and adolescents who do not get regular sunlight exposure, do not ingest at least 32 ounces per day of vitamin D-fortified milk, or do not take a daily multivitamin supplement containing at least 400 IU of vitamin D.

Others have suggested a bolus dosing 150,000 IU each autumn for those in northern climates.¹⁷

Most over-the-counter vitamin formulations now contain D₃ (cholecalciferol), as recent studies show this form is more potent than D₂ (ergocalciferol).¹⁸ Calcium supplements are available in combination with vitamin D. Calcitriol, the most active form of vitamin D, is available only by prescription. Because it does not require activation in the kidneys, it is the drug of choice for renally impaired patients.

Q: How would you treat this child?

Bad taste is a big hurdle

The child in this case was prescribed 150,000 U oral cholecalciferol. She spit it out at the clinic, and the dose was sent home for her parents to administer. She was also started on a multivitamin (Poly-Vi-Sol). On the return visit a few days later, the parents reported that she only took three-quarters of the vitamin D dose, spitting out the remainder.

When that didn’t work…

The child was then admitted to the hospital for administration of vitamin D and to allow for dietary and social work evaluations of factors contributing to her malnutrition.

Social services evaluation ruled out an economic etiology for the child’s failure to thrive. The family was able to afford a nutritionally adequate diet for the child. They were enrolled in Medicaid and WIC. Willful neglect was not an issue: A very loving and appropriate relationship was evident between the child and her parents. Child care was shared equally by the young parents, but they simply didn’t know what foods were appropriate for a child of her age.

Turning things around

The hospital dietician observed one of the child’s meals. The child ate some of everything on the plate: mashed potatoes and gravy, chicken strips, vegetables, bananas, yogurt, and milk. She was willing to try a variety of foods, and ate most of them. Both the physician and the dietician spent a lot of time with the parents reviewing feeding techniques and healthy food choices. Language was a problem, solved for the most part with the assistance of a dial-up language translation service to ensure clear understanding of the instructions. The health care professionals prepared a list of healthy foods to buy at the grocery store, with pictures illustrating healthy food items. In addition, appropriate exposure to sunlight was explained and encouraged.

Parent education is the key

The child’s father expressed gratitude several times for the instruction on healthy food choices for the daughter, while the mother smiled in shy agreement. He said they did not know what to feed her, and when she refused most things they offered, they fed her the noodles and juice she seemed to prefer. He was grateful to the nutritionist, social worker, nursing staff, and physicians for taking care of his daughter. He was eager to go to the grocery store and to start feeding her the “right foods.”

Ready to go home

By discharge, the child had received the full dose of vitamin D and was eating a variety of foods, including 1 to 4 ounces of milk daily, supplemented with Poly-Vi-Sol, 1 mL orally twice daily, and calcium carbonate (OsCal) with vitamin D, 1 crushed tablet orally twice daily. Home health nursing provided follow-up twice a week, and weekly appointments in the clinic with the physician were also scheduled. Compliance with the discharge plan was impeccable. Both laboratory and clinical signs of rickets resolved over the subsequent weeks.

A 13-month-old girl arrives at your clinic, referred by the staff at the Women, Infants, and Children (WIC) nutritional center where her parents—recent immigrants from Africa—go for food supplements. The baby is bundled up in layers of clothing, even though it’s a relatively mild winter day. The father carries her into the examining room and undresses her. The child is tiny and dark-skinned, with curly hair painstakingly divided into little bunches. The parents seem caring, loving, and not particularly worried. They tell you the nurse at the WIC center thought their baby was not gaining enough weight and advised them to bring the baby to you. The referral note from WIC says hemoglobin levels found on routine blood test were low. You list the presenting complaint as anemia.

Q: What are some of the etiologies for anemia in a child this age? What strategies would you use to narrow down the cause?

Additional medical history

• The birth history is unremarkable, with neither antepartum nor postpartum complications.
• At her 6-month well-child checkup, neither the child’s physician nor her parents expressed any concerns about her development. Her parents received the routine anticipatory guidance at that visit, including advice on breastfeeding, vitamin supplementation, vaccination, and care of minor illnesses.
• She hasn’t been in for a well-child visit since then, but she has been seen for an upper respiratory infection and a bout of gastroenteritis. Her parents have not been worried about her health.
• The parents tell you the baby doesn’t sleep soundly, scratches her skin in her sleep, and cries a lot.

Family and social history

• The parents speak very little English.
• The patient is an only child, and no extended family live in the area.
• Her mother works nights and her father works days, with the parent who is not working caring for her at home.
• Her parents tell you she takes small sips of juice or water, and an occasional bite of noodles. She won’t drink milk at all and refuses any other foods they offer.

Physical examination

• The child is in no acute distress. She is afebrile, and her vital signs are appropriate for her age.
• Height is 27½ inches, weight 15 lb, 15 oz, placing her at less than the 5th percentile for height and weight for her age—a regression from the 50th percentile she showed at earlier visits.
• Head and neck exam reveals mild frontal bossing and prominent sternoclavicular joints. There is no adenopathy or thyromegaly.
• Heart and lung exam are normal.
• Abdomen is soft, nontender, nondistended, with bowel sounds present.
• There is slight bowing of the lower extremities and puffiness around the wrists and ankles. When you ask her father to have her stand on the examining table, you see that she needs support to do so (FIGURE 1).

Q: What is your clinical diagnosis, and what tests will you order?

FIGURE 1
The patient, not weight-bearing

Laboratory results

• Hemoglobin, 9.9 mg/dL
  (normal: 10.4-12.4 mg/dL)
• Mean corpuscular volume (MCV), 74 fL
  (normal: 70-86 fL)
• Alkaline phosphatase, 3417 U/L
  (normal: 115-460 U/L)
• Vitamin D (calcidiol), <7 nmol/L
  (normal: 60-108 nmol/L)
• Calcium, 9.1 mg/dL
  (normal: 8.8-10.8 mg/dL)
• Comprehensive metabolic panel, liver transaminases, and thyroid-stimulating hormone levels are all normal
• Parathyroid hormone level, 101 pg/mL
  (normal: 10-55 pg/mL).

Radiologic findings

• X-ray shows slight saber deformity of the femurs and broadening of the epiphyses of the forearm (FIGURE 2).

FIGURE 2
Forearm x-ray

Can this be rickets?

Here is a child with a history of poor growth and peculiar eating habits. Her legs are bowed and her wrists seem swollen. She does not stand or walk, and refuses to bear weight on her legs. She is anemic, and the lab tests you’ve ordered show abnormal vitamin D, alkaline phosphatase, and parathyroid hormone levels. All of this suggests a diagnosis of rickets.

Causes of rickets

Rickets is the result of abnormal mineralization of bone and cartilage in growing children. The analogous condition in adults whose epiphyseal plates have closed is osteomalacia. Clinical rickets typically presents with the constellation of signs and symptoms listed in the box and depicted in FIGURES 1, 2, and 3.

FIGURE 3
Rachitic rosary

Not enough vitamin D

The most common cause of rickets is a deficiency of vitamin D, a substance physiologically necessary to produce concentrations of calcium and phosphate adequate for proper bone mineralization. Vitamin D is produced in the skin in the presence of sunlight and can also be ingested in supplements and certain foods.

Vitamin D deficiency may result from reduced sunlight exposure, inadequate dietary intake, malabsorption, or a combination of these factors.¹ Rickets may also be caused by medications that alter absorption or secretion of phosphate and calcium, including antacids, anticonvulsants, corticosteroids, and loop diuretics. Various disease states, such as Crohn’s disease, pancreatic disease, biliary disease, gastrointestinal loops and fistulae, cirrhosis, chronic renal disease, and mesenchymal tumors, may also alter absorption and metabolism of these ions.

How much sunshine does a baby need?

It doesn’t take a great deal of sunlight exposure to provide adequate supplies of vitamin D. An infant wearing only a diaper will get enough vitamin D from half an hour per week of sun exposure. A fully clothed infant needs 3 hours. But children with dark skin, like this African baby, need more time in the sun. And if parents follow current anticipatory guidance about protecting children from overexposure to the sun and slather on the sunscreen, vitamin D synthesis decreases by more than 95%.²

Vitamin D in the diet

Consuming adequate quantities of vitamin D is difficult, unless the diet includes fortified foods or vitamin supplements. Current recommendations for daily intake are 400 IU per day for all infants, children, and adolescents.³ But the average daily intake by adults in North America from sources such as fish, eggs, and butter or margarine is only 50 to 100 IU.³

Infants born to vitamin-D replete women have an 8- to 12-week store of vitamin D at birth, but breastfeeding does not ensure the baby is getting adequate amounts of vitamin D, even if the mother’s vitamin D status is adequate. Human milk from vitamin D-replete women has a vitamin D concentration of only 25 IU per liter, far below the recommended daily intake of 400 IU.³

How deficient is this baby?

Vitamin D deficiency may be categorized as mild, moderate, or severe. Calcidiol is the next-to-last step in the metabolism of vitamin D and is used as a marker because it is easier to measure than the concentration of calcitriol, the final step. Mild vitamin D deficiency is defined as serum calcidiol concentration of 25 to 50 nmol/L. A serum calcidiol concentration of 12.5 to 25 nmol/L indicates a moderate vitamin D deficiency, and at those levels the incidence of hypocalcemia and rickets increases. Serum calcidiol concentration of less than 12.5 nmol/L, as in the case of the patient presented here, indicates a severe deficiency.⁴

Not enough calcium

In addition to calcium malabsorption due to inadequate vitamin D levels, hypocalcemia may result from inadequate intake of calcium or from vitamin D-dependent metabolic disorders, of which there are 2 types.

Type I, sometimes known as pseudo-vitamin D-deficiency rickets, is due to defective production of 25(OH)D₃-1-α-hydroxylase, an enzyme necessary for the conversion of calcidiol to calcitriol in the kidneys.

Type II, also called hereditary rickets, is rare. It is caused by mutations in vitamin D receptors and the inability of the ligand to bind or stimulate the proper physiologic response. In this condition, laboratory tests may show high levels of calcitriol.

Not enough phosphorus

Vitamin D-resistant rickets, or familial hypophosphatemic rickets, refers to a clinical presentation of rickets that is caused by a hereditary renal wasting of phosphorus at the proximal tubule level. Laboratory evaluation of a child with this condition will show low phosphate levels, normal calcitriol levels, and hypercalciuria. The specific defect that causes this condition is not known. A family history of short stature, orthopedic abnormalities, poor dentition, alopecia, or parental consanguinity may be suggestive of vitamin D-dependent or vitamin D-resistant forms of inherited rickets.

Other causes of hypophosphatemia include inadequate nutritional intake, X-linked hypophosphatemia, generalized tubular disorders such as renal tubular acidosis, Fanconi syndrome, and Dent disease. These disorders may also lead to rickets.

Q: What are the available treatments for rickets? What about prevention?

Replenishing vitamin D

Vitamin D deficiency may be remedied by supplementing anywhere along the metabolic pathway. Dihydrotachysterol (DHT, or D₁), the substance in the skin that responds to sunlight, is given as 60,000 IU once, then 6000 IU daily until the rickets are clinically and radiologically resolved. Further downstream, ergocalciferol (D₂) may be given as 1000 to 5000 IU daily for 6 to 12 weeks. The dosage is calibrated by age: 1000 IU/d if age <1 month, 3000 IU/d for ages 1 to 12 months, and 5000 IU/d for children older than 12 months. The final form of vitamin D is cholecalciferol (D₃). This is typically administered as either 5000 to 10,000 IU daily for 2 to 3 months, or as 600,000 IU in 1 day, divided into 4 to 6 doses.^5,6 All of these supplements taste bad and children are often resistant to swallowing them.

When follow-up and multiple dosing are impractical—because the family finds repeated clinic visits too difficult, or because the child will not comply with the regimen—you can use stosstherapy.⁷ This is a bolus of cholecalciferol (D₃) or ergocalciferol (D₂), 150,000 to 600,000 IU, given as a single dose or divided over several days. For example, you would give 300,000 IU over 1 to 7 days in children 1 to 12 months of age. With this therapy, onset of action is less than a day and maximal effects are seen in 4 weeks. Some preparations contain propylene glycol, which is limited in food additives to <25 mg/kg of body weight because of potential toxicity.

When supplementation doesn’t work. Vitamin D is not effective in treatment of familial hypophosphatemic rickets, Type II vitamin D-dependent rickets, or disorders of phosphate metabolism.

Monitoring therapeutic success

When possible, treatment should be monitored by checking serum calcium and alkaline phosphatase at 1 month, and calcium, magnesium, phosphate, alkaline phosphatase, calcidiol, parathyroid hormone, and wrist x-ray at 3 months from initiation of treatment, to ensure that they are normalizing.

Preventing rickets

In the developed world, public health efforts to prevent rickets have been largely successful. Rickets was prevalent worldwide in the early decades of the 20th century, but after milk began to be routinely fortified with vitamin D in the 1920s, cases of nutritional rickets almost disappeared in industrialized nations.

In 1963, the American Academy of Pediatrics (AAP) began recommending vitamin D supplementation to prevent rickets. Although the recommendation remains controversial because of concerns about the possibility of hypervitaminosis and the resultant hypercalcemia and hypercalciuria, there has been renewed emphasis on this recommendation in light of a rise in the number of cases of rickets in the United States in recent years.^8-14 Current AAP recommendations for vitamin D supplementation are daily supplementation of 400 IU vitamin D for the following groups:³

• Breastfed infants, beginning with the first few days of life and continued until they are weaned to at least 1000 mL per day of vitamin D-fortified formula or milk.
• Nonbreastfed infants who are ingesting less than 1000 mL per day of vitamin D-fortified formula or milk. Most commercial baby formulas contain 400 IU/L, which means that an intake of 500 mL of formula per day provides 200 IU.¹⁵ Additionally, special milk supplemented with vitamin D₃ up to 200 IU per 250 mL has recently become available in Europe.¹⁶
• Children and adolescents who do not get regular sunlight exposure, do not ingest at least 32 ounces per day of vitamin D-fortified milk, or do not take a daily multivitamin supplement containing at least 400 IU of vitamin D.

Others have suggested a bolus dosing 150,000 IU each autumn for those in northern climates.¹⁷

Most over-the-counter vitamin formulations now contain D₃ (cholecalciferol), as recent studies show this form is more potent than D₂ (ergocalciferol).¹⁸ Calcium supplements are available in combination with vitamin D. Calcitriol, the most active form of vitamin D, is available only by prescription. Because it does not require activation in the kidneys, it is the drug of choice for renally impaired patients.

Q: How would you treat this child?

Bad taste is a big hurdle

The child in this case was prescribed 150,000 U oral cholecalciferol. She spit it out at the clinic, and the dose was sent home for her parents to administer. She was also started on a multivitamin (Poly-Vi-Sol). On the return visit a few days later, the parents reported that she only took three-quarters of the vitamin D dose, spitting out the remainder.

When that didn’t work…

The child was then admitted to the hospital for administration of vitamin D and to allow for dietary and social work evaluations of factors contributing to her malnutrition.

Social services evaluation ruled out an economic etiology for the child’s failure to thrive. The family was able to afford a nutritionally adequate diet for the child. They were enrolled in Medicaid and WIC. Willful neglect was not an issue: A very loving and appropriate relationship was evident between the child and her parents. Child care was shared equally by the young parents, but they simply didn’t know what foods were appropriate for a child of her age.

Turning things around

The hospital dietician observed one of the child’s meals. The child ate some of everything on the plate: mashed potatoes and gravy, chicken strips, vegetables, bananas, yogurt, and milk. She was willing to try a variety of foods, and ate most of them. Both the physician and the dietician spent a lot of time with the parents reviewing feeding techniques and healthy food choices. Language was a problem, solved for the most part with the assistance of a dial-up language translation service to ensure clear understanding of the instructions. The health care professionals prepared a list of healthy foods to buy at the grocery store, with pictures illustrating healthy food items. In addition, appropriate exposure to sunlight was explained and encouraged.

Parent education is the key

The child’s father expressed gratitude several times for the instruction on healthy food choices for the daughter, while the mother smiled in shy agreement. He said they did not know what to feed her, and when she refused most things they offered, they fed her the noodles and juice she seemed to prefer. He was grateful to the nutritionist, social worker, nursing staff, and physicians for taking care of his daughter. He was eager to go to the grocery store and to start feeding her the “right foods.”

Ready to go home

By discharge, the child had received the full dose of vitamin D and was eating a variety of foods, including 1 to 4 ounces of milk daily, supplemented with Poly-Vi-Sol, 1 mL orally twice daily, and calcium carbonate (OsCal) with vitamin D, 1 crushed tablet orally twice daily. Home health nursing provided follow-up twice a week, and weekly appointments in the clinic with the physician were also scheduled. Compliance with the discharge plan was impeccable. Both laboratory and clinical signs of rickets resolved over the subsequent weeks.

A 57-year-old woman with a history of breast cancer comes to your office complaining of pain and swelling on the left side of her neck. She has recently had a mastectomy and chemotherapy; her port was removed in the past week. She has no chills, cough, dyspnea, palpitations, chest pain, nausea, weight gain, edema, or urinary complaints. She is, however, experiencing mild, general fatigue and a “scratchy throat”; otherwise there are no systemic symptoms. She is worried that her “cancer has come back.”

Other medical history

• Hypothyroidism and hypertension
• History of deep venous thrombosis (DVT) attributed to her cancer; was on warfarin but “held” last week for her port removal surgery.
• Remote history of cholecystectomy
• No known drug allergies
• No history of myocardial infarction, congestive heart failure, stroke, or diabetes
• No recent international travel
• Current medications: anastrozole, hydrochlorothiazide, levothyroxine, calcium, warfarin, epoetin alfa, and acetaminophen

Family and social history

• Family history is significant for coronary artery disease late in life in her parents
• No family history of cancer, blood dyscrasia, or immunocompromise
• Formerly a smoker, only recently quit
• Moderate caffeine intake (coffee)
• Employed as a banker

Physical examination

• Temperature 99.7°F, pulse 92, respirations 20, blood pressure 122/74 mm Hg, weight 130 lbs
• Alert, oriented, no distress, full affect
• PERRLA (pupils equal, round, reactive to light and accommodation), extraocular motions intact, cranial nerves II–XII intact, mucous membranes moist, pharynx clear, no carotid bruits, minimal cervical adenopathy
• There is a tender, ill-defined mass on the left side of the neck, extending from angle of the mandible to the clavicle behind which it disappears
• Heart regular without murmurs or enlargement
• Lungs clear to auscultation in all fields
• Operative site on the left anterior thorax (port removal) is clean, dry, nonerythematous, healing well
• Abdomen is soft, nontender, nondistended, no organomegaly, normal bowel sounds
• Extremities show no significant edema or venous distention

Lab results

• White bloods cell count elevated at 13 (3.9–10.9), 76% neutrophils with no bands
• Mild anemia of 11.3 (11.7–16.0)
• International normalized ratio (INR)= 0.94
• Blood cultures are pending
• Rapid strep test is negative

Next step: Order imaging studies

This particular presentation prompts you to order a computed tomography (CT) scan of her neck and chest, looking for a specific pathology (FIGURE 1).

When the scan is complete, the radiologist calls and confirms that there is occlusion of the left internal jugular vein, brachiocephalic vein, and a portion of the left subclavian vein with thrombosis.

A second CT of the chest again reveals the thrombosed veins, but there are no filling defects suggestive of pulmonary emboli or peripheral infiltrates or cavitary lesions suggestive of septic emboli (FIGURE 2).

You vaguely recall that jugular thrombophlebitis is associated with some syndrome, so you turn to UpToDate and do a search on “jugular thrombophlebitis.”

There you learn that Lemierre’s syndrome, also known as necrobacillosis, is septic thrombophlebitis of the jugular vein. It most commonly develops following pharyngitis, and has been associated with dental microbes.^1,2

Similar syndromes of suppurative thrombophlebitis may also occur in peripheral veins, associated with intravenous catheterization (especially PICC lines³), the superior and inferior vena cava, always associated with central lines,⁴ and the ovarian veins.⁵

FIGURE 1 Thrombosed veins

CT image with IV contrast of the base of the neck showing thrombosed veins.

FIGURE 2 Collateral circulation

This 3D reconstruction of CT images shows the extensive collateral circulation on the left, compared with the right.

You caught it early

Suppurative thrombophlebitis. This problem often presents with fever and rigorous chills. Swelling and tenderness is noted over the affected vein in about half the cases. Obviously, though, inspection and palpation of the vena cava is challenging and such signs do not apply when these vessels are involved.

Respiratory distress due to septic pulmonary emboli and secondary pneumonia is common. Metastatic abscess formation at other sites, such as joint and bone, have been reported.^1,6

You realize that most patients with suppurative thrombophlebitis present in a much more toxic state than yours did. Perhaps you caught it early. She certainly has risk factors, including her recent pharyngitis and central venous catheterization. The prominent collateral circulation raises the possibility that this may have developed subacutely, following a more indolent course than is generally reported.

The organisms responsible for suppurative thrombophlebitis depend on the infection’s site of origin. Most of the time in the peripheral veins or vena cava, Staphylococcus, a member of normal skin flora, is the pathogen. Streptococcus, Enterobacteriaceae, Candida, and even cytomegalovirus have been documented.^4,7,8 Jugular septic thrombophlebitis draws from the oral flora, with the most common causative agent being the anaerobic Fusobacterium.

A thrombus provides an excellent source of nutrients for the microbes, which colonize it and establish what is essentially a biofilm. These complex microbial architectures are extraordinarily resistant to antibiotic therapy, especially when compared with plantonic bacteria.⁹ Not only does the thrombus facilitate the infection, but the bacteria facilitate thrombus formation by promoting platelet aggregation.¹⁰

Central venous access: Ensuring proper care

Chemotherapy is only one of the many circumstances in which central venous access is required. Central venous access devices (CVADs) are also used for administration of antibiotics, hydration, total parenteral nutrition, or long-term blood sampling.

The central lines that most family physicians learned to insert during residency are only one of a dizzying array of CVADs in use. The triple-lumen lines are inserted transcutaneously by the resident into either the jugular or subclavian veins and are good for short-to-medium duration therapies. They require diligent care to prevent occlusion or infection, including daily flushing.

For longer-duration therapies, tunneled catheters may be placed, typically by surgical consultants. These are less prone to bleeding or infection but still require diligent attention and regular flushing. Some models do permit weekly flushing.

Peripherally-inserted central venous catheters (PICCs) may be used for up to a year. Generally inserted by nursing staff, they are still fairly high-maintenance and require daily flushes.

Representative venous access devices. Clockwise from upper left: triple lumen catheter, tunneled catheter, subcutaneous port, PICC.

Your patient had a subcutaneous CVAD, which is often called a “port.” It is surgically implanted, not unlike a pacemaker, and is ideal for long-term use, especially when required access is intermittent. It requires flushing only monthly (weekly when being accessed).

Medication or surgery?

Because of its resistance to antibiotic treatment, peripheral venous suppurative thrombophlebitis is a surgical disease, not unlike an abscess, and requires excision or incision and drainage of the affected vessel. Antibiotics alone are inadequate. Excision of thrombophlebitis of the central veins affected is not feasible (though thrombectomies are occasionally undertaken). In this case, prolonged antibiotic therapy is indicated.

Anticoagulation may also be considered, though no strong evidence supports that addition. Given the effect of Fusobacterium on platelet aggregation, aspirin might be expected to provide benefit. In vitro studies show inhibition of this aggregation with aspirin,¹⁰ but no clinical studies or even case reports indicate improved outcomes with its use.

A hospital stay

Prolonged antibiotics

You admit the patient to the hospital with a presumptive diagnosis of Lemierre’s syndrome and begin piperacillin/tazobactam intravenously, covering both Fusobacterium and Staphlococcus. You also opt to begin heparin and resume her warfarin, more for her history of DVT than because of documented benefit of anticoagulation in the management of suppurative thrombophlebitis.

Anticoagulation

Over the course of her hospital stay, she spikes a fever (≥100°F) every 24 hours for the first 5 days, after which the peak temperatures slowly drop to normal. She reaches therapeutic levels on warfarin and the heparin is discontinued. At no point do any respiratory symptoms develop. Aerobic blood cultures show no growth; to your chagrin, you find out that anaerobic cultures were not obtained. After 8 days, the patient’s neck is no longer tender, the swelling has gone down, she’s adequately anticoagulated, has been afebrile for 48 hours, and is extremely eager to go home.

She is discharged with a prescription of amoxicillin/clavulanate 3 times daily for 4 weeks, as the literature suggests that most Fusobacterium are sensitive to this agent.¹¹ She is instructed to return if any recurrent fevers, chest pain, or respiratory symptoms develop. At a routine follow-up appointment in a month, she remains asymptomatic.

A 57-year-old woman with a history of breast cancer comes to your office complaining of pain and swelling on the left side of her neck. She has recently had a mastectomy and chemotherapy; her port was removed in the past week. She has no chills, cough, dyspnea, palpitations, chest pain, nausea, weight gain, edema, or urinary complaints. She is, however, experiencing mild, general fatigue and a “scratchy throat”; otherwise there are no systemic symptoms. She is worried that her “cancer has come back.”

Other medical history

• Hypothyroidism and hypertension
• History of deep venous thrombosis (DVT) attributed to her cancer; was on warfarin but “held” last week for her port removal surgery.
• Remote history of cholecystectomy
• No known drug allergies
• No history of myocardial infarction, congestive heart failure, stroke, or diabetes
• No recent international travel
• Current medications: anastrozole, hydrochlorothiazide, levothyroxine, calcium, warfarin, epoetin alfa, and acetaminophen

Family and social history

• Family history is significant for coronary artery disease late in life in her parents
• No family history of cancer, blood dyscrasia, or immunocompromise
• Formerly a smoker, only recently quit
• Moderate caffeine intake (coffee)
• Employed as a banker

Physical examination

• Temperature 99.7°F, pulse 92, respirations 20, blood pressure 122/74 mm Hg, weight 130 lbs
• Alert, oriented, no distress, full affect
• PERRLA (pupils equal, round, reactive to light and accommodation), extraocular motions intact, cranial nerves II–XII intact, mucous membranes moist, pharynx clear, no carotid bruits, minimal cervical adenopathy
• There is a tender, ill-defined mass on the left side of the neck, extending from angle of the mandible to the clavicle behind which it disappears
• Heart regular without murmurs or enlargement
• Lungs clear to auscultation in all fields
• Operative site on the left anterior thorax (port removal) is clean, dry, nonerythematous, healing well
• Abdomen is soft, nontender, nondistended, no organomegaly, normal bowel sounds
• Extremities show no significant edema or venous distention

Lab results

• White bloods cell count elevated at 13 (3.9–10.9), 76% neutrophils with no bands
• Mild anemia of 11.3 (11.7–16.0)
• International normalized ratio (INR)= 0.94
• Blood cultures are pending
• Rapid strep test is negative

Next step: Order imaging studies

This particular presentation prompts you to order a computed tomography (CT) scan of her neck and chest, looking for a specific pathology (FIGURE 1).

When the scan is complete, the radiologist calls and confirms that there is occlusion of the left internal jugular vein, brachiocephalic vein, and a portion of the left subclavian vein with thrombosis.

A second CT of the chest again reveals the thrombosed veins, but there are no filling defects suggestive of pulmonary emboli or peripheral infiltrates or cavitary lesions suggestive of septic emboli (FIGURE 2).

You vaguely recall that jugular thrombophlebitis is associated with some syndrome, so you turn to UpToDate and do a search on “jugular thrombophlebitis.”

There you learn that Lemierre’s syndrome, also known as necrobacillosis, is septic thrombophlebitis of the jugular vein. It most commonly develops following pharyngitis, and has been associated with dental microbes.^1,2

Similar syndromes of suppurative thrombophlebitis may also occur in peripheral veins, associated with intravenous catheterization (especially PICC lines³), the superior and inferior vena cava, always associated with central lines,⁴ and the ovarian veins.⁵

FIGURE 1 Thrombosed veins

CT image with IV contrast of the base of the neck showing thrombosed veins.

FIGURE 2 Collateral circulation

This 3D reconstruction of CT images shows the extensive collateral circulation on the left, compared with the right.

You caught it early

Suppurative thrombophlebitis. This problem often presents with fever and rigorous chills. Swelling and tenderness is noted over the affected vein in about half the cases. Obviously, though, inspection and palpation of the vena cava is challenging and such signs do not apply when these vessels are involved.

Respiratory distress due to septic pulmonary emboli and secondary pneumonia is common. Metastatic abscess formation at other sites, such as joint and bone, have been reported.^1,6

You realize that most patients with suppurative thrombophlebitis present in a much more toxic state than yours did. Perhaps you caught it early. She certainly has risk factors, including her recent pharyngitis and central venous catheterization. The prominent collateral circulation raises the possibility that this may have developed subacutely, following a more indolent course than is generally reported.

The organisms responsible for suppurative thrombophlebitis depend on the infection’s site of origin. Most of the time in the peripheral veins or vena cava, Staphylococcus, a member of normal skin flora, is the pathogen. Streptococcus, Enterobacteriaceae, Candida, and even cytomegalovirus have been documented.^4,7,8 Jugular septic thrombophlebitis draws from the oral flora, with the most common causative agent being the anaerobic Fusobacterium.

A thrombus provides an excellent source of nutrients for the microbes, which colonize it and establish what is essentially a biofilm. These complex microbial architectures are extraordinarily resistant to antibiotic therapy, especially when compared with plantonic bacteria.⁹ Not only does the thrombus facilitate the infection, but the bacteria facilitate thrombus formation by promoting platelet aggregation.¹⁰

Central venous access: Ensuring proper care

Chemotherapy is only one of the many circumstances in which central venous access is required. Central venous access devices (CVADs) are also used for administration of antibiotics, hydration, total parenteral nutrition, or long-term blood sampling.

The central lines that most family physicians learned to insert during residency are only one of a dizzying array of CVADs in use. The triple-lumen lines are inserted transcutaneously by the resident into either the jugular or subclavian veins and are good for short-to-medium duration therapies. They require diligent care to prevent occlusion or infection, including daily flushing.

For longer-duration therapies, tunneled catheters may be placed, typically by surgical consultants. These are less prone to bleeding or infection but still require diligent attention and regular flushing. Some models do permit weekly flushing.

Peripherally-inserted central venous catheters (PICCs) may be used for up to a year. Generally inserted by nursing staff, they are still fairly high-maintenance and require daily flushes.

Representative venous access devices. Clockwise from upper left: triple lumen catheter, tunneled catheter, subcutaneous port, PICC.

Your patient had a subcutaneous CVAD, which is often called a “port.” It is surgically implanted, not unlike a pacemaker, and is ideal for long-term use, especially when required access is intermittent. It requires flushing only monthly (weekly when being accessed).

Medication or surgery?

Because of its resistance to antibiotic treatment, peripheral venous suppurative thrombophlebitis is a surgical disease, not unlike an abscess, and requires excision or incision and drainage of the affected vessel. Antibiotics alone are inadequate. Excision of thrombophlebitis of the central veins affected is not feasible (though thrombectomies are occasionally undertaken). In this case, prolonged antibiotic therapy is indicated.

Anticoagulation may also be considered, though no strong evidence supports that addition. Given the effect of Fusobacterium on platelet aggregation, aspirin might be expected to provide benefit. In vitro studies show inhibition of this aggregation with aspirin,¹⁰ but no clinical studies or even case reports indicate improved outcomes with its use.

A hospital stay

Prolonged antibiotics

You admit the patient to the hospital with a presumptive diagnosis of Lemierre’s syndrome and begin piperacillin/tazobactam intravenously, covering both Fusobacterium and Staphlococcus. You also opt to begin heparin and resume her warfarin, more for her history of DVT than because of documented benefit of anticoagulation in the management of suppurative thrombophlebitis.

Anticoagulation

Over the course of her hospital stay, she spikes a fever (≥100°F) every 24 hours for the first 5 days, after which the peak temperatures slowly drop to normal. She reaches therapeutic levels on warfarin and the heparin is discontinued. At no point do any respiratory symptoms develop. Aerobic blood cultures show no growth; to your chagrin, you find out that anaerobic cultures were not obtained. After 8 days, the patient’s neck is no longer tender, the swelling has gone down, she’s adequately anticoagulated, has been afebrile for 48 hours, and is extremely eager to go home.

She is discharged with a prescription of amoxicillin/clavulanate 3 times daily for 4 weeks, as the literature suggests that most Fusobacterium are sensitive to this agent.¹¹ She is instructed to return if any recurrent fevers, chest pain, or respiratory symptoms develop. At a routine follow-up appointment in a month, she remains asymptomatic.

A 57-year-old woman with a history of breast cancer comes to your office complaining of pain and swelling on the left side of her neck. She has recently had a mastectomy and chemotherapy; her port was removed in the past week. She has no chills, cough, dyspnea, palpitations, chest pain, nausea, weight gain, edema, or urinary complaints. She is, however, experiencing mild, general fatigue and a “scratchy throat”; otherwise there are no systemic symptoms. She is worried that her “cancer has come back.”

Other medical history

• Hypothyroidism and hypertension
• History of deep venous thrombosis (DVT) attributed to her cancer; was on warfarin but “held” last week for her port removal surgery.
• Remote history of cholecystectomy
• No known drug allergies
• No history of myocardial infarction, congestive heart failure, stroke, or diabetes
• No recent international travel
• Current medications: anastrozole, hydrochlorothiazide, levothyroxine, calcium, warfarin, epoetin alfa, and acetaminophen

Family and social history

• Family history is significant for coronary artery disease late in life in her parents
• No family history of cancer, blood dyscrasia, or immunocompromise
• Formerly a smoker, only recently quit
• Moderate caffeine intake (coffee)
• Employed as a banker

Physical examination

• Temperature 99.7°F, pulse 92, respirations 20, blood pressure 122/74 mm Hg, weight 130 lbs
• Alert, oriented, no distress, full affect
• PERRLA (pupils equal, round, reactive to light and accommodation), extraocular motions intact, cranial nerves II–XII intact, mucous membranes moist, pharynx clear, no carotid bruits, minimal cervical adenopathy
• There is a tender, ill-defined mass on the left side of the neck, extending from angle of the mandible to the clavicle behind which it disappears
• Heart regular without murmurs or enlargement
• Lungs clear to auscultation in all fields
• Operative site on the left anterior thorax (port removal) is clean, dry, nonerythematous, healing well
• Abdomen is soft, nontender, nondistended, no organomegaly, normal bowel sounds
• Extremities show no significant edema or venous distention

Lab results

• White bloods cell count elevated at 13 (3.9–10.9), 76% neutrophils with no bands
• Mild anemia of 11.3 (11.7–16.0)
• International normalized ratio (INR)= 0.94
• Blood cultures are pending
• Rapid strep test is negative

Next step: Order imaging studies

This particular presentation prompts you to order a computed tomography (CT) scan of her neck and chest, looking for a specific pathology (FIGURE 1).

When the scan is complete, the radiologist calls and confirms that there is occlusion of the left internal jugular vein, brachiocephalic vein, and a portion of the left subclavian vein with thrombosis.

A second CT of the chest again reveals the thrombosed veins, but there are no filling defects suggestive of pulmonary emboli or peripheral infiltrates or cavitary lesions suggestive of septic emboli (FIGURE 2).

You vaguely recall that jugular thrombophlebitis is associated with some syndrome, so you turn to UpToDate and do a search on “jugular thrombophlebitis.”

There you learn that Lemierre’s syndrome, also known as necrobacillosis, is septic thrombophlebitis of the jugular vein. It most commonly develops following pharyngitis, and has been associated with dental microbes.^1,2

Similar syndromes of suppurative thrombophlebitis may also occur in peripheral veins, associated with intravenous catheterization (especially PICC lines³), the superior and inferior vena cava, always associated with central lines,⁴ and the ovarian veins.⁵

FIGURE 1 Thrombosed veins

CT image with IV contrast of the base of the neck showing thrombosed veins.

FIGURE 2 Collateral circulation

This 3D reconstruction of CT images shows the extensive collateral circulation on the left, compared with the right.

You caught it early

Suppurative thrombophlebitis. This problem often presents with fever and rigorous chills. Swelling and tenderness is noted over the affected vein in about half the cases. Obviously, though, inspection and palpation of the vena cava is challenging and such signs do not apply when these vessels are involved.

Respiratory distress due to septic pulmonary emboli and secondary pneumonia is common. Metastatic abscess formation at other sites, such as joint and bone, have been reported.^1,6

You realize that most patients with suppurative thrombophlebitis present in a much more toxic state than yours did. Perhaps you caught it early. She certainly has risk factors, including her recent pharyngitis and central venous catheterization. The prominent collateral circulation raises the possibility that this may have developed subacutely, following a more indolent course than is generally reported.

The organisms responsible for suppurative thrombophlebitis depend on the infection’s site of origin. Most of the time in the peripheral veins or vena cava, Staphylococcus, a member of normal skin flora, is the pathogen. Streptococcus, Enterobacteriaceae, Candida, and even cytomegalovirus have been documented.^4,7,8 Jugular septic thrombophlebitis draws from the oral flora, with the most common causative agent being the anaerobic Fusobacterium.

A thrombus provides an excellent source of nutrients for the microbes, which colonize it and establish what is essentially a biofilm. These complex microbial architectures are extraordinarily resistant to antibiotic therapy, especially when compared with plantonic bacteria.⁹ Not only does the thrombus facilitate the infection, but the bacteria facilitate thrombus formation by promoting platelet aggregation.¹⁰

Central venous access: Ensuring proper care

Chemotherapy is only one of the many circumstances in which central venous access is required. Central venous access devices (CVADs) are also used for administration of antibiotics, hydration, total parenteral nutrition, or long-term blood sampling.

The central lines that most family physicians learned to insert during residency are only one of a dizzying array of CVADs in use. The triple-lumen lines are inserted transcutaneously by the resident into either the jugular or subclavian veins and are good for short-to-medium duration therapies. They require diligent care to prevent occlusion or infection, including daily flushing.

For longer-duration therapies, tunneled catheters may be placed, typically by surgical consultants. These are less prone to bleeding or infection but still require diligent attention and regular flushing. Some models do permit weekly flushing.

Peripherally-inserted central venous catheters (PICCs) may be used for up to a year. Generally inserted by nursing staff, they are still fairly high-maintenance and require daily flushes.

Representative venous access devices. Clockwise from upper left: triple lumen catheter, tunneled catheter, subcutaneous port, PICC.

Your patient had a subcutaneous CVAD, which is often called a “port.” It is surgically implanted, not unlike a pacemaker, and is ideal for long-term use, especially when required access is intermittent. It requires flushing only monthly (weekly when being accessed).

Medication or surgery?

Because of its resistance to antibiotic treatment, peripheral venous suppurative thrombophlebitis is a surgical disease, not unlike an abscess, and requires excision or incision and drainage of the affected vessel. Antibiotics alone are inadequate. Excision of thrombophlebitis of the central veins affected is not feasible (though thrombectomies are occasionally undertaken). In this case, prolonged antibiotic therapy is indicated.

Anticoagulation may also be considered, though no strong evidence supports that addition. Given the effect of Fusobacterium on platelet aggregation, aspirin might be expected to provide benefit. In vitro studies show inhibition of this aggregation with aspirin,¹⁰ but no clinical studies or even case reports indicate improved outcomes with its use.

A hospital stay

Prolonged antibiotics

You admit the patient to the hospital with a presumptive diagnosis of Lemierre’s syndrome and begin piperacillin/tazobactam intravenously, covering both Fusobacterium and Staphlococcus. You also opt to begin heparin and resume her warfarin, more for her history of DVT than because of documented benefit of anticoagulation in the management of suppurative thrombophlebitis.

Anticoagulation

Over the course of her hospital stay, she spikes a fever (≥100°F) every 24 hours for the first 5 days, after which the peak temperatures slowly drop to normal. She reaches therapeutic levels on warfarin and the heparin is discontinued. At no point do any respiratory symptoms develop. Aerobic blood cultures show no growth; to your chagrin, you find out that anaerobic cultures were not obtained. After 8 days, the patient’s neck is no longer tender, the swelling has gone down, she’s adequately anticoagulated, has been afebrile for 48 hours, and is extremely eager to go home.

She is discharged with a prescription of amoxicillin/clavulanate 3 times daily for 4 weeks, as the literature suggests that most Fusobacterium are sensitive to this agent.¹¹ She is instructed to return if any recurrent fevers, chest pain, or respiratory symptoms develop. At a routine follow-up appointment in a month, she remains asymptomatic.