Compare indications, dosing, and efficacy of unfractionated heparin and low molecular weight heparin.

Implement evidence-based practice guidelines for the management of community-acquired pneumonia and Clostridium difficile-associated diarrhea.

Diagnose and treat patients with osteoporosis.

Prevent contrast-induced nephropathy.

Perform preoperative risk stratification and identify patients who may benefit from revascularization, β- blocker therapy, or prophylaxis to prevent endocarditis.

Hospital Medicine Update
Bradley A. Sharpe, MD, Assistant Clinical Professor, Division of Hospital Medicine, University of California, San Francisco, School of Medicine

Prophylaxis for venous thromboembolism (VTE) in medical patients: pulmonary embolism (PE)— autopsy studies suggest 10% of inpatient deaths caused by PEs that occur during stay (75% occur in medical patients); heparin—unfractionated heparin (UFH) and low molecular weight heparin (LMWH) decrease risk for deep venous thrombosis (DVT) and PE, but not death, and increase risk for major and minor bleeding; for UHF, tid dosing better (more effective; similar rate of adverse effects) than bid dosing; LMWH does not increase risk for thrombocytopenia (not reported in studies using UHF); LMWH vs UFH—LMWH associated with lower risk for DVT at all doses and lower risk for injection-site hematoma; rates of PE, bleeding, death, and thrombocytopenia similar (nonsignificant trend toward decreased thrombocytopenia with LMWH); some studies show better cost-effectiveness of LMWH (more expensive but fewer adverse effects), but recent meta-analysis found no differences in rates of adverse effects

Community-acquired pneumonia (CAP): duration of antibiotic therapy—meta-analysis of 15 randomized controlled trials (RCTs) compared short (≤7 days) with extended (\>7 days) courses of various antibiotics in patients with uncomplicated mild to moderate CAP; nonsignificant trend toward less clinical failure with short courses (for all classes of antibiotics studied); no differences in bacterial response or rates of adverse effects; studies not powered to assess differences in rates of resistance; shortcomings of study include underrepresentation of older adults and absence of data on some antibiotics (eg, doxycycline); guidelines from Infectious Disease Society of America state minimum duration of 5 days (7 days standard); extended course reserved for patients with complications or more severe illness (eg, empyema, bacteremia, extended fever); pneumococcal vaccine—not shown to reduce mortality or prevent pneumonia, but large prospective study showed vaccinated patients had lower rates of admission to intensive care unit (ICU; ie, decreased disease severity) than unvaccinated patients

Severe Clostridium difficile-associated diarrhea (CDAD): case—patient on antibiotic therapy for CAP develops diarrhea, fever, abdominal pain, and tachycardia; white blood cell (WBC) count, 28000 cells/µL; severe CDAD suspected; treatment—standard of care oral metronidazole, but supported by little evidence; RCT compared oral metronidazole with oral vancomycin (10-day courses) for patients with confirmed CDAD; severe CDAD defined as requiring admission to ICU, having evidence of pseudomembranous colitis on colonoscopy or sigmoidoscopy, or having ≥2 risk factors for poor outcome (age \>60 yr; fever; high WBC count; low albumin level); cure rates similar among patients with mild disease, but vancomycin superior for patients with severe disease (cure rate 21% higher; no differences in adverse events or rates of relapse); practice recommendations—use vancomycin for patients with severe disease; use metronidazole (much less expensive) for patients with mild disease; probiotics—study found supplementation with Lactobacillus associated with statistically significant reduction in antibiotic-associated diarrhea and CDAD

Enoxaparin for patients with non–ST-elevation myocardial infarctions (NSTEMIs): case—woman, 89 yr of age, 45 kg, has chest pain and shortness of breath; physical examination unremarkable; electrocardiography (ECG) shows lateral ST-depressions; elevated troponin level (4.5 mg/dL); dosing—twice daily dose of 1 mg/kg recommended; patients with chronic kidney disease should receive once-daily dosing; large, multicenter, observational study looked at dosing practices and patient outcomes; ≈20% of patients overdosed (received >10 mg/day more than recommended; especially common among patients with renal insufficiency); ≈30% of patients underdosed (received >10 mg/day less than recommended); overdosing increased rates of bleeding and mortality by ≥2-fold; underdosing associated with nonsignificant increase in death; practice recommendations—dose LMWH according to guidelines; consider creatinine clearance and adjust dose according to package insert or switch to UFH; get accurate weight of patient to ensure correct dose

Preoperative management of patients with high cardiovascular (CV) risk: stress testing—dobutamine echocardiography previously recommended for high-risk patients before vascular surgery; revascularization—Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo (DECREASE)-V trial (pilot study) compared revascularization (eg, percutaneous coronary intervention; coronary artery bypass graft) to medical therapy for high-risk patients undergoing vascular surgery (75% of patients had severe disease); medical therapy associated with nonsignificant trend toward decreased mortality at 1 mo and 1 yr (ie, no benefit seen with revascularization); larger study in progress; caveat—results suggest absence of benefit of prophylactic revascularization, but should not be extrapolated to patients with indications for stress test or catheterization

Management of osteoporosis: hip fracture after fall from standing indicates osteoporosis and requires treatment; zoledronic acid—Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly (HORIZON) trial studied effect of annual administration of zoledronic acid within 90 days after surgery for hip fracture; all patients received calcium and vitamin D supplementation; compared to placebo, zoledronic acid reduces risk for all fractures and mortality, with number needed to treat (NNT) of 27; no difference in rates of adverse effects, including atrial fibrillation; unknown whether benefit extends to all bisphosphonates or limited to intravenous (IV) zoledronic acid; practice recommendations—all patients with osteoporotic hip fracture should receive calcium and vitamin D supplementation and bisphosphonate therapy; hip protectors—study found no benefit among nursing home residents at high risk for falls

Pulmonary embolism: risk factors for VTE—major risk factors include malignancy, history of surgery, and hypercoagulable states; case-control study showed DVT and PE more common among patients with recent history of minor injury to lower extremities (eg, ankle or knee sprain, pulled muscle; patients in casts or with extended immobilization excluded); risk especially high among those patients homozygous for factor V Leiden gene; troponins—meta-analysis of 20 studies showed that elevated levels of troponins (in setting of PE) associated with higher rates of adverse events and mortality; elevations may indicate right-heart strain; good practice to check troponin levels in all patients with PE (may help with risk stratification); diagnostic tests—computed tomographic angiography (CTA) faster and simpler than pulmonary ventilation-perfusion (V/Q) scans; study randomized patients with high pretest probabilities for PE to CTA or V/ Q; tests equally sensitive for ruling out PE; CTA detected more subsegmental PEs (questionable clinical relevance)

Contrast-induced nephropathy (CIN): young patients with normal levels of creatinine have very low risk; risk factors include age, heart failure, diabetes, and history of kidney disease; if creatinine increases after exposure to contrast, length of stay and complication rates increase (risk for in-hospital death also may increase); prevention strategies—use low-osmolar contrast; decrease contrast load; hydrate patient (with, eg, saline); meta-analysis—41 trials; most patients at relatively high risk (eg, chronic kidney disease; advanced age) and underwent cardiac catheterization; CIN defined as creatinine increased by 0.5 mg/dL or \>25% within 48 hr after contrast exposure; all patients received hydration; treatment with N-acetylcysteine (NAC) associated with decreased rate of CIN (relative risk [RR] 0.62); theophylline associated with nonsignificant reduction in RR (0.5); furosemide (eg, Lasix) contraindicated in patients with risk for CIN; note, studies did not assess impact on mortality or need for dialysis; practice recommendations—in addition to hydration, give oral NAC (inexpensive; very few adverse effects) to patients at medium-to-high risk for CIN; hydration solution— Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL) compared different hydration solutions to NAC in ≈300 patients with chronic renal insufficiency (average baseline creatinine, 2 mg/dL) undergoing cardiac catheterization; NAC with bicarbonate associated with fewer episodes of CIN (defined as 25% rise in creatinine) than NAC with normal saline (NNT, 13); addition of ascorbic acid to normal saline and NAC had no benefit

Summary: measure troponins in patients with acute PE; consider diagnosis of VTE in patients with recent minor injury to lower extremity; use NAC and hydrate patients with bicarbonate solution to reduce risk for CIN; initiate heparin therapy in appropriate medical patients (LMWH preferred in many settings); treat patients with severe CDAD with vancomycin; encourage use of pneumococcal vaccine; prescribe 7-day courses for most patients with mild to moderate CAP; initiate bisphosphonate therapy after osteoporotic hip fracture; limit revascularization to patients likely to benefit; dose enoxaparin appropriately

Update in Perioperative Medicine for Office-based Internists
Hugo Quinny Cheng, MD, Associate Clinical Professor, Division of Hospital Medicine, University of California, San Francisco, School of Medicine

Perioperative β-blockade: supporting evidence—RCT looked at effect of bisoprolol in 111 patients (not previously on β-blockers) with ischemia on dobutamine echocardiography and at high risk for postoperative death or MI (after vascular surgery); patients randomized to bisoprolol or placebo and followed for 30 days after surgery (follow-up included serial ECGs and cardiac enzyme assays); 34% of patients receiving placebo but only 3.5% of patients receiving bisoprolol died or suffered nonfatal MI (NNT, 3)

Contradictory evidence: Metoprolol after Vascular Surgery (MaVS) study—metoprolol did not significantly decrease 30-day rates of fatal or nonfatal cardiac outcomes after vascular surgery, when started immediately before surgery and continued for 5 days; treatment with metoprolol associated with increased risk for bradycardia and clinically significant hypotension; note, study participants had different risk profiles than those in previous study; Perioperative Ischemia Evaluation (POISE) study—RCT looked at effect of metoprolol XL in \>8000 patients (not previously on β-blockers) undergoing major surgery (vascular and nonvascular); patients had coronary disease, peripheral vascular disease, or multiple revised cardiac risk index (RCRI) risk factors; metoprolol XL started immediately before surgery and continued for 30 days; metoprolol associated with small decrease in 30-day cardiac mortality and nonfatal MI, but total mortality showed small increase (mostly caused by stroke); higher risk for ischemic stroke likely due to β-blocker–induced hypotension in patients with cerebrovascular risk factors

Practice recommendations: continue β-blockers in patients already on β-blocker therapy; initiate β-blockers before major vascular surgery in patients with ischemic potential; consider initiating β-blockers before high-risk nonvascular surgery (eg, long duration; significant loss of blood) in patients with ischemic potential, and before any high-risk surgery in patients with multiple risk predictors; when initiating β-blocker before surgery, start with low dose (weeks to months before surgery), titrate slowly to appropriate dose, and monitor for bradycardia and hypotension

Prophylaxis for endocarditis: antibiotic prophylaxis no longer recommended in many settings previously considered indications (eg, tooth extraction, colonoscopy with polypectomy, laparoscopic cholecystectomy); bacteremia from daily activities (eg, brushing and flossing teeth) more likely to cause endocarditis than procedures; prophylaxis prevents few cases of endocarditis; 2007 guidelines from American Heart Association—prophylaxis recommended only for patients with conditions associated with high risk for poor outcomes after endocarditis; prophylaxis limited to procedures involving mouth and upper respiratory tract; high-risk conditions include presence of prosthetic valve or history of endocarditis; prophylaxis not indicated for patients with minor cardiac problems (eg, degenerative aortic stenosis, ischemic mitral regurgitation; mitral valve prolapse); antibiotics—2 g oral amoxicillin preferred; options for patients with penicillin allergy include oral cephalexin (2 g), clindamycin (600 mg), azithromycin (500 mg), or clarithromycin (500 mg); for parenteral administration, use intramuscular or IV ampicillin (2 g), cefazolin (1 g), ceftriaxone (1 g), or clindamycin (600 mg)

B-type natriuretic peptide (BNP) and surgical risk: elevated preoperative levels of BNP associated with higher risk for poor outcomes; studies—among 170 patients undergoing vascular surgery, N-terminal pro-BNP (NT-proBNP) \>533 pg/mL associated with increased risk for cardiac complications (high predictive value); another study found BNP level of 40 pg/mL to be best cutoff for assessing risk among patients undergoing various types of major surgery; BNP may be more accurate than clinical risk assessment; unanswered questions—appropriate cutoff and possibility of variance among populations; role in overall risk assessment (eg, risk stratification) and management (eg, direct decisions about stress testing or surgery)

Statins to prevent postoperative cardiac complications: retrospective and observational studies suggest that statins may reduce risk for postoperative death or MI; RCT also found benefit (fewer nonfatal MIs); DECREASE-IV trial (ongoing) looking at effects of bisoprolol and/or fluvastatin in patients undergoing major surgery; statin withdrawal— increasing evidence of harm; prospective cohort study showed that interruption of statin treatment (in patients undergoing vascular surgery) associated with 7-fold increased risk for cardiac death or MI; effect persisted after controlling for confounders and propensity score