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Update in hospital medicine highlights sepsis, community-acquired pneumonia

New research could help guide treatment

By Jennifer Kearney-Strouse

From the July ACP Hospitalist, copyright © 2008 by the American College of Physicians

Sidebar: Studies cited

Sepsis, community-acquired pneumonia and stroke were among the topics covered at this year’s “Update in Hospital Medicine” at Internal Medicine 2008. Joseph M. Li, ACP Member, director of the hospital medicine program at Beth Israel Deaconess Medical Center in Boston, and Jeffrey Glasheen, FACP, director of the hospital medicine program at the University of Colorado Denver, discussed new research that could help guide hospitalists’ clinical practice.

Steroids, glucose control in sepsis

A low-dose steroid did not improve mortality in patients with sepsis, according to findings from the CORTICUS trial (N Engl J Med 2008; 358:111-24), which compared intravenous hydrocortisone with placebo. Patients in the hydrocortisone group had faster shock reversal but also had higher rates of hyperglycemia and hypernatremia, higher rates of superinfection and higher rates of new septic shock than those in the placebo group. Although a French study published in the Journal of the American Medical Association in 2002 did show a mortality benefit with steroids, Dr. Li pointed out that the patient population in that study was sicker.

“Steroids may have a role in the sickest patients with septic shock, but certainly in less-sick patients, they may not have a role.” —Joseph M. Li, ACP Member

“The takeaway is that steroids may have a role in the sickest patients with septic shock, but certainly in less-sick patients, they may not have a role,” he said. He also noted that physicians should consider using hydrocortisone for septic shock only in patients refractory to fluids and vasopressors.

Conflicting data on intensive insulin control have created a conundrum for hospitalists, Dr. Li said: “Do we just tightly manage our surgical ICU population but not tightly manage our medical ICU population?” In addition, in patients with septic shock, the data have been insufficient to guide use of colloids or crystalloids for fluid resuscitation, he noted.

A recent trial by Brunkhorst and colleagues (N Engl J Med 2008; 358:125-39) addressed these questions by examining the safety of intensive insulin therapy in patients with severe sepsis or septic shock, as well as which method of fluid resuscitation was better (modified lactated ringers or 10% pentastarch). The intensive glucose therapy arm was stopped after the first safety analysis because of higher rates of hypoglycemia, while the fluid resuscitation comparison continued with all patients receiving conventional insulin therapy. The study was stopped completely at the planned interim analysis because of an increased incidence of renal failure in the pentastarch group and a higher 90-day mortality rate.

The study findings didn’t completely invalidate the idea of maintaining tight blood sugar control in hospitalized patients, according to Dr. Li. “What this study tells us is that, in many of our hospitals today, we simply don’t have an environment that deals adequately in terms of controlling tight blood sugars,” he said. “Perhaps in the future, if we’re able to change that environment, the study results might be different. But certainly, at this time, it would suggest that in a medical ICU population, in patients with sepsis and shock, intensive insulin therapy is fraught with some danger with hypoglycemia.”

Currently, a blood glucose goal of 150 mg/dL or less is more appropriate than lower goals, Dr. Li noted. In addition, he said, physicians should probably stop using pentastarch in patients with septic shock.

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Duration and timing of therapy in community-acquired pneumonia

A meta-analysis by Li and colleagues (Am J Med 2007; 120:783-90) compared short-course antibiotic therapy (seven days or less) with longer-term antibiotic therapy (more than seven days) for community-acquired pneumonia (CAP) and found that duration made little difference. Regardless of the type of antibiotic therapy, Dr. Li said, “macrolides, fluoroquinolones or beta-lactam, the risk of clinical failure was very similar regardless of whether it was short-course versus extended-course therapy.”

This study showed that extended-course antibiotic therapy doesn’t seem to improve clinical outcomes in mild to moderate CAP, Dr. Li said. However, he pointed out that elderly patients were underrepresented in the meta-analysis and that some antibiotics, such as doxycycline, were not evaluated. He also noted that the trial does not apply to patients with severe pneumonia.

In 2003, The Joint Commission and CMS instituted the controversial “four-hour rule,” mandating that patients with suspected CAP receive antibiotic therapy within four hours of presentation. A retrospective study by Kanwar and colleagues (Chest 2007; 161:1865-9) compared 107 patients who received care in 2003, before the rule took effect, with 210 patients who received care in 2005. More patients received antibiotics within four hours in 2005 than in 2003, but substantially fewer patients (59% vs. 76%) received a final diagnosis of CAP.

“This mandate from CMS and JCAHO resulted in inappropriate utilization of antibiotics in our patients,” Dr. Li said. “Now they have broadened it to a six-hour window, and it certainly appears that six hours would be more appropriate.”

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Anticoagulation in cardioembolic stroke

Dr. Glasheen discussed a meta-analysis by Paciaroni and colleagues (Stroke 2007; 38:423-30) that aimed to determine the safety and efficacy of anticoagulation in the treatment of cardioembolic stroke.

“The data leading up to this was all over the place,” Dr. Glasheen said. “There were some studies that showed there was definite benefit to anticoagulating these patients within 48 hours, there were studies that showed no benefit, and there were studies that actually showed harm.”

The 2007 study examined the seven existing randomized, controlled trials and compared full-dose anticoagulation to aspirin or placebo for initial therapy. No statistically significant difference was seen in death, disability, new stroke or pulmonary embolism, but patients receiving anticoagulation were nearly threefold more likely to have an intracranial hemorrhage than those receiving aspirin or placebo.

“I think we’re starting to get the sense that anticoagulation in the acute setting of an acute stroke is probably not beneficial, although at the same time we understand that chronic anticoagulation, especially in those with afib, is beneficial,” Dr. Glasheen said. “So the question is, ‘What’s the optimal timing of that transition when someone’s had an acute stroke with atrial fibrillation?’ and the answer is that we don’t really know.”

The authors of the 2007 study suggested that it’s reasonable to start warfarin when a patient is neurologically and medically stable and has a negative CT scan showing no hemorrhagic transformation. At Dr. Glasheen’s institution, patients are discharged on warfarin with or without a follow-up CT scan. “Now, is that data-driven? Not really, but then again neither is the recommendation that these authors are making. They’re basically giving their opinion,” he said.

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Enoxaparin dosing in patients with NSTEMI

Incorrect enoxaparin dosing is common in patients with non-ST-segment elevation MI, according to an observational study from the CRUSADE initiative (Arch Intern Med 2007; 167:1539-44). Researchers examined the association between enoxaparin dosing and bleeding or death in 10,687 patients from 32 hospitals and found that 20% received an overdose and 30% received an underdose. Those who received overdoses were twice as likely to have major bleeding and were also 2.5 times more likely to die than those who got the recommended dose. In addition, 60% of patients who had a creatinine clearance under 30 mL/min received an overdose, which indicates that physicians should carefully estimate renal function when prescribing this drug, Dr. Glasheen noted. “In patients with a depressed [glomerular filtration rate] below 30, the right dose of enoxaparin is actually 1 mg/kg per day, not twice a day,” he said.

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Prescribing zoledronic acid after hip fracture

Lyles and colleagues (N Engl J Med 2007; 357:1799-809) randomly assigned 2,127 patients to receive yearly intravenous zoledronic acid or placebo after hip fracture. Rates of both fracture and mortality were lower in the zoledronic acid group at one year, suggesting that bisphosphonates may be a helpful addition to calcium plus vitamin D in hip fracture patients. Hospitalists should consider prescribing a bisphosphonate before the patient leaves the hospital, Dr. Glasheen recommended.

“One of the concerns the orthopedic surgeons will have is that this will impair wound healing, or at least bone healing. In this study it didn’t appear that that was the case, so it’s probably safe in the hospital,” he said. “But definitely make sure it’s in your discharge summary and that patients are getting it in clinic.”

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Studies cited

Sprung CL et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358:111-24.
Brunkhorst FM et al. N Engl J Med 2008; 358:125-39. Intensive insulin therapy and pentastarch resuscitation in severe sepsis.
Li JZ et al. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am J Med 2007; 120:783-90.
Kanwar M et al. Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-h antibiotic administration rule. Chest 2007; 131:1865-9.
Paciaroni M et al. Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials. Stroke 2007; 38:423-30.
LaPointe NM et al. Enoxaparin dosing and associated risk of in-hospital bleeding and death in patients with non ST-segment elevation acute coronary syndromes. CRUSADE initiative. Arch Intern Med 2007; 167:1539-44.
Lyles KW et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007; 357:1799-809.

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ACP Hospitalist provides news and information for internists about the practice of medicine and reports on the policies, products and activities of ACP. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated