Home Feature The year’s most influential studies

The year’s most influential studies

July 2008

Published in the July 2008 issue of Today’s Hospitalist

Which studies published in the past year have had the biggest impact on hospitalist practice? To answer that question, two hospitalists “Joseph Li, MD, of Boston’s Beth Israel Deaconess Hospital and Jeffrey Glasheen, MD, of the University of Colorado, Denver “presented a series of cases at this spring’s Society of Hospital Medicine annual meeting. Those cases were designed to illustrate how the latest evidence can be turned into clinical practice.

CASE 1
ONE: On admission, a 63-year-old woman with hypertension shows signs of septic shock secondary to community-acquired pneumonia (CAP). After being given fluids and norepinephrine, she remains hypotensive. Should you add a vasopressin to increase her mean arterial pressure?

No. The Vasopressin and Septic Shock Trial (VASST), published in the Feb. 28, 2008, New England Journal of Medicine (NEJM), concluded that there was no mortality difference when patients with septic shock were given norepinephrine or vasopressin. Instead, a better course of action would be to increase the norepinephrine infusion.

TWO: The patient’s hypotension improves with increased norepinephrine, but she remains critically ill. Should you give her steroids?

Probably not. And don’t order an ACTH stimulation test either.

The Corticosteroid Therapy of Septic Shock (CORTICUS) study, published in the Jan. 10, 2008, issue of NEJM, found that giving patients in septic shock low-dose hydrocortisone did not improve survival and, in fact, increased adverse events. (Hydrocortisone did, however, reverse shock more quickly for some.)

The study also showed that it won’t help to know if the patient will respond to an ACTH stimulation test. Because a smaller previous study, which looked at sicker patients, found that low-dose steroids did help, there may be some septic shock patients, particularly those who don’t respond to fluids and vasopressors, who should receive steroids.

THREE: The patient finally stabilizes in the ICU. She is intubated and on norephinephrine and antibiotics, but now her blood sugar level is 215 mg/dL. Do you want to start an insulin drip? And if you do, what should your goal be?

Yes, you should start a drip. But set a goal of 150 mg/dL and don’t use
Pentastarch.

A study published in the Jan. 10, 2008, issue of NEJM found that intensive insulin therapy with a goal of 80-110 mg/dL placed critically ill medical patients with sepsis at increased risk for serious adverse events related to hypoglycemia. The trial was stopped early for safety reasons.

That intensive insulin regimen had been promoted after a much cited 2001 Dutch study of critically ill surgical patients found that achieving the lower goal reduced in-hospital mortality from 10.9% to 7.2%. The new study also found that using Pentastarch was associated with serious side effects.

FOUR: After four days, the patient is so much better that she is transferred out of the ICU. But a few days later, she develops fever, abdominal pain and diarrhea. You suspect a severe C. difficile infection. Should you prescribe metronidazole or vancomycin?

Vancomycin. A study in the Aug. 1, 2007, issue of Clinical Infectious Diseases compared vancomycin and metronidazole for the treatment of C. diff.-associated diarrhea. It found that for severe cases, vancomycin worked better, producing a cure rate of 97% vs. 76%. For mild cases, however, the study concluded that the two drugs worked equally well.

CASE 2
ONE: An 82-year-old man comes to the hospital complaining that for the last five hours, he has had right-sided upper extremity weakness and dysarthria. A head CT shows no acute bleed. Is he a candidate for recombinant tissue plasminogen activator (tPA)?

No, but only because it’s too late.

The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) trial, published in the Jan. 27, 2007, issue of The Lancet, confirmed that IV tPA is safe and effective in routine clinical use when used within three hours of ischemic stroke onset. That was true even in centers that had little previous experience with thrombolytic therapy for acute stroke. The authors concluded
that their “findings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.”

TWO: Unfortunately, this patient is outside the three-hour time window. Should he receive therapeutic anticoagulation in addition to aspirin?

No. A meta-analysis of all randomized controlled trials on the safety and efficacy of anticoagulation in treating acute stroke was published in the February 2007 issue of Stroke.

It concluded that early anticoagulation, within 48 hours of the stroke, neither improved recurrence of ischemic stroke nor substantially reduced death and disability.

Early anticoagulation, however, increased intracranial bleeding. The only anticoagulation that should occur, therefore, is unfractionated or low-molecular-weight heparin given at VTE prophylactic doses.

As an aside, another study published in the Aug. 11, 2007, issue of The Lancet found that warfarin was safe to prescribe to patients older than age 75 who have atrial fibrillation.

CASE 3
ONE: An 82-year-old diabetic, hypertensive woman comes to the ED after several hours of chest pressure and shortness of breath. She is diagnosed with non-ST elevation myocardial infarction (NSTEMI) and prescribed aspirin, metoprolol, nitroglycerin and enoxaparin. Is a dose of 60 mg subcutaneous enoxaparin twice daily correct?

No. A study published in the July 23, 2007, Archives of Internal Medicine found a relationship among enoxaparin dose, bleeding and outcomes in NSTEMI. Almost one out of every five patients was being overdosed, and 30% were underdosed.

In addition, patients with renal insufficiency have decreased enoxaparin clearance, which makes it particularly important to review renal function and adjust doses accordingly. The recommended daily dose of enoxaparin sodium is 2 mg/kg for patients with a creatinine clearance of 30 mL/min or greater, and 1 mg/kg for patients with a creatinine clearance of less than 30 mL/min.

TWO: After you adjust the patient’s enoxaparin dose and no bleeding complications occur, the patient is sent for cardiac catheterization. Multiple 60% lesions are seen, but none requires intervention, and she goes home on appropriate medical therapy. A year and a half later, she is being scheduled for femoral-popliteal bypass surgery. Does she need a stress test or cath before surgery?

Probably not. A pilot study in the Netherlands (known as the DECREASE-V) study was written up in the May 1, 2007, Journal of the American College of Cardiology. Investigators asked whether patients with extensive coronary artery disease, who are classified by ACC/AHA guidelines as being at increased risk of perioperative cardiac complications, would benefit from prophylactic coronary revascularization before getting major vascular surgery. The study found that preoperative coronary revascularization did not improve outcomes.

Although this study was small and cannot necessarily be extrapolated to the U.S., hospitalists should consider not revascularizing patients prior to surgery unless patients would need such a procedure anyway.

THREE: After surgery, the woman does well, but a year later she breaks her hip and undergoes an uncomplicated hip arthroplasty. On discharge, should you advise her to do anything to keep her from breaking bones in the future?

Yes. Consider giving her a shot of zoledronic acid right now, and recommend that she get one once a year.

A study published in the Nov. 1, 2007, NEJM concluded that an annual infusion of zoledronic acid both reduced the rate of new clinical fractures and improved survival. The study found that for every 27 patients treated with this once-a-year IV medication, one fracture can be averted. The drug also does not affect bone healing, so it can be given within 90 days after repair of a low-trauma hip fracture.

CASE 4
ONE: A 65-year-old female smoker with diabetes and congestive heart failure comes to the hospital complaining of shortness of breath and a cough. She is diagnosed with CAP, and her pneumonia severity index score is 85. She gets her first dose of antibiotics within four hours and is admitted to the hospitalist service. How long should she stay on antibiotics?

A short course of seven days or less is probably OK.

A meta-analysis published in the September 2007 issue of the American Journal of Medicine found no difference in clinical outcomes, including bacteriologic eradication and mortality, or in clinical failure when patients with mild to moderate CAP were treated with either short or long courses of antibiotics.

Does it matter if the first dose is delivered within four hours of hospital arrival? A study in the June 1, 2007, issue of Chest concluded that using that measure as an indicator of hospital quality results in overdiagnosis of CAP and inappropriate utilization of antibiotics.

As a result, many now consider a more appropriate goal to be giving antibiotics within six hours of hospital arrival. (See “New thinking on antibiotic timing in CAP patients” in the March 2008 Today’s Hospitalist.)

TWO: Now that she is your patient, what venous thromboembolism (VTE)
prophylaxis should you order?

Prescribe either unfractionated or low-molecular-weight heparin. According to a meta-analysis in the July 23, 2007, Archives of Internal Medicine, both forms of heparin reduce VTE risk in hospitalized medical patients. However, neither agent alters mortality, and both increase risks of major bleeding.

Deborah Gesensway is a freelance writer who reports on U.S. health care from Toronto, Canada.