Published in the June/July 2004 issue of Today’s Hospitalist
For inpatient physicians working on the front lines of hospital care, 2003 was anything but quiet. The year was punctuated by a number of notable developments in and new thinking about best clinical practices in a wide range of areas, from pulmonary disease management to cardiovascular-event prevention. There was also the year’s biggest scare story, the emergence of severe acute respiratory syndrome (SARS).
At the annual meeting of the Society of Hospital Medicine in New Orleans, two speakers covered this and more during an update on hospital medicine. Chad Whelan, MD, of the University of Chicago, and Lisa Kettering, MD, of Exempla-Saint Joseph Hospital in Denver, recapped the year’s biggest news as it unfolded in key clinical studies.
Here’s a look at some of the most significant studies they summarized, along with take-home points for hospitalists.
Annals of Internal Medicine 2003: 138:861-870
Which patients with acute exacerbations of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation?
While several studies have shown that noninvasive positive-pressure ventilation can reduce mortality in COPD patients, Dr. Whelan said few have addressed issues of tolerance and disease severity.
After reviewing 15 different trials, researchers identified several significant results:
- Noninvasive positive-pressure ventilation is associated with a significant decrease in in-hospital mortality rates. Researchers found an absolute risk reduction of 10 percent and a 28 percent lower risk of intubation.
- Length of stay was reduced with noninvasive positive-pressure ventilation as measured by an absolute reduction of 4.57 days.
Dr. Whelan noted that the benefits of noninvasive positive-pressure ventilation are seen primarily in patients with severe COPD exacerbations. He added that individuals with mild to moderate disease did not appear to benefit from the intervention.
Annals of Internal Medicine 2003: 138:494-501
Prevention of ventilator-associated pneumonia: an evidence-based systematic review
While ventilator-associated pneumonia (VAP) is problematic and occurs in 10 percent to 25 percent of ventilated patients, it is preventable. The condition is also associated with mortality rates that range from 5 percent to 27 percent.
This review study looked at several VAP interventions and their effect on reducing rates of ventilator-associated pneumonia. Researchers found the following:
- Semi-recumbant positioning was found to provide a preventive benefit in three trials without associated adverse effects.
- In meta-analyses of 20 randomized trials, stress-ulcer prophylaxis with sulcrafate reduced overall mortality rates more effectively than H2 blockers. The latter, however, may not be as effective as H2 blockers in preventing the ulcers.
- Sub-glottic secretion aspiration yielded a significant VAP reduction in only one of the studies. Dr. Whelan noted that the specialized endotracheal tubes used cost approximately 25 percent more than standard tubes.
- Oscillating beds produced a benefit in only two types of patients: post-surgical patients and individuals with neurological deficit. Complications, however, were notable. Some patients did not tolerate the beds, Dr. Whelan said, and the beds also contributed to the disconnection of important catheters.
- Digestive tract decontamination lowered VAP-associated mortality between 37 percent and 42 percent, and it reduced antibiotic costs and hospital costs by 20 percent. Nonetheless, Dr. Whelan said that the strategy is not recommended because of concerns about antibiotic resistance.
- Ventilator circuit management strategies demonstrated no VAP reduction, but researchers found no adverse effects.
- Methods of enteral feeding, specifically the use of approaches such as small-intestinal feeding and acidification of feeding, did not provide a benefit.
Because of the high incidence of VAP in critically ill patients, Dr. Whelan said, further studies and development of novel interventions are needed.
New England Journal of Medicine 2003: 349:1695-1702
Subcutaneous fondaparinux versus intravenous unfractionatedheparin in theinitial treatment of pulmonary embolism
This major randomized trial of 2,213 hemodynamically stable patients with acute pulmonary embolism found no significant differences between fondaparinux and heparin. Researchers, however, found that fondaparinux did appear to provide a slight benefit in reducing recurrent venous thromboembolism.
“The bottom line is that there was no difference in effectiveness between the two groups,” Dr. Whelan said. He noted, however, that while the study was not primarily designed to look at safety, there were no differences in bleeding rates or overall mortality between the two study groups.
He added that the study’s inference that fondaparinux might be safe to administer in the outpatient setting should be viewed with caution.
JAMA 2003: 289:553-558
Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial
This randomized, placebo-controlled trial of 200 patients sought to determine if acetylcysteine can protect against acute contrast agent-mediated renal dysfunction in patients who undergo elective cardiac angiography.
Patients with stable chronic renal insufficiency received either 600 mg of acetylcysteine or placebo prior to the procedure. They also received a single post-procedure dose.
Researchers found the following in subjects who received acetylcysteine:
- Acute contrast-induced renal dysfunction was reduced 12 percent, a number that was statistically significant.
- On average, length of stay was 0.5 days shorter.
- Subjects who received acetylcysteine had better serum creatinine levels, but only a slight improvement in creatinine clearance.
As no major adverse events were seen with acetylcysteine use, Dr. Whelan said, the drug appears to be both safe and effective. He added that it should be given in conjunction with IV hydration.
Archives of Internal Medicine 2003: 163:1849-1856
Argatroban anticoagulation in patients with heparin-induced thrombocytopenia
This prospective, multicenter observational study of 418 patients looked at the efficacy of the new drug argatroban in preventing death and new thrombotic events. Researchers focused on inpatients who develop heparin-induced thrombocytopenia (HIT), a potentially catastrophic disease, or HIT with thrombosis.
Researchers discovered that argatroban was associated with several benefits:
- The drug significantly improved important outcomes “death, amputation or new thrombotic events “in HIT patients.
- There was no significant difference in all-cause mortality.
- There were fewer thrombosis-related deaths in patients with HIT with thrombosis.
“Argatroban is a reasonable option for HIT,” Dr. Whelan said. “It was associated with a marked decline in thrombotic death and a big decline in thrombotic events. Given the catastrophic nature of the disease, we’ll probably never see a randomized, controlled trial.”
Annals of Internal Medicine 2003: 138:445-452
Implantable cardioverter defibrillators in primary and secondary prevention: a systematic review of randomized, controlled trials
This review compared the efficacy of implantable cardioverter defibrillators to standard antiarrhythmic drugs or placebo for primary or secondary prevention of sudden cardiac death and all-cause mortality. Researchers focused on eight trials involving a total of 4,909 patients over a 22-year period.
Researchers discovered the following about implantable cardioverter defibrillators:
- The devices are effective in reducing risk of sudden cardiac death (relative reduction of 50 percent) and all-cause mortality (relative reduction of 30 percent).
- Defibrillators are effective in secondary prevention for both sudden cardiac death and for all-cause mortality. In primary prevention, defibrillators showed efficacy in sudden cardiac death for both high- and moderate-risk patients, but efficacy in primary prevention for all-cause mortality was only seen in those at high baseline risk.
Dr. Kettering said that while the study points to benefits of implanting defibrillators in certain groups of patients, further studies are needed to accurately stratify patients according to baseline risk. “We also need to address the cost effectiveness of this issue and the quality of life after ICD implantation,” she said.
New England Journal of Medicine 2003: 348:1309-1321
Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction
In this landmark randomized, placebo-controlled trial of 6,632 patients with MI and left ventricular dysfunction, subjects in the study group received 25 mg daily of eplerenone, up to a maximum of 50 mg daily, between three and 14 days after MI.
Researchers found the following benefits in subjects who received eplerenone:
- Death rates from cardiovascular causes were lower in the eplerenone patients (12.3 percent vs. 14.6 percent).
- Any-cause death rates were lower in the eplerenone group (14.4 percent vs. 16.7 percent).
- Higher rates of serious hyperkalemia were found in the eplerenone patients (5.5 percent vs. 3.9 percent), primarily in subjects with lower baseline creatinine clearance.
“The take-home point is that eplerenone reduces morbidity and mortality in patients with heart failure and LV dysfunction following MI,” Dr. Kettering said. “It may be considered at additional therapy for patients already receiving optimal medical therapy.”
She cautioned, however, that concerns about hyperkalemia may necessitate excluding patients who have moderate to severe renal insufficiency. She also added that the hyperkalemia risk may be reduced by administering eplerenone in the dose range of 25-50 mg.
Lancet 2003: 362:789-797
Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomized controlled trial
In this randomized, placebo-controlled trial, 1,883 patients received the study drug in four oral doses “24 mg, 36 mg, 48 mg or 60 mg twice daily “for six months following MI. Patients also took 160 mg daily of aspirin.
The primary composite endpoint was efficacy in reducing all-cause mortality, non-fatal MI and severe recurrent ischemia. The study also addressed safety and tolerability of ximelagatran.
Researchers found the following:
- For combined dosing groups, ximelagatran reduced the composite endpoint of all-cause mortality, non-fatal MI and recurrent ischemia more effectively than aspirin alone.
- The drug did not increase the risk of major bleeding, but it did increase the risk of total bleeding, a difference that appeared to be dose-related, with the 24 mg dose being safest.
- Alanine transaminase (ALT) concentrations increased significantly in patients taking ximelagatran, but this effect was typically without clinical sequelae.
Dr. Kettering noted that while the drug does not appear to increase major bleeding events, both total bleeding events and high ALT concentrations appeared to be related to dosing. “Further trials are needed to determine whether ximelagatran alleviates the inconvenience of blood monitoring associated with other oral anticoagulant therapy,” she said.
Annals of Internal Medicine 2003: 139:715-723
Outcomes and prognostic factors in 267 patients with severe acute respiratorysyndrome in Hong Kong
“No 2003 hospital medicine update would be complete without mention of SARS,” Dr. Kettering said in introducing her summary of this retrospective cohort study involving 267 patients.
Of the subjects studied, 227 of whom had confirmed SARS, 52 percent were related to the Amoy Garden outbreak in Hong Kong. Nine percent worked in health care.
In culling through data, researchers found the following:
- Nearly all patients (99 percent) had fever at presentation and 74 percent had chills. Other key common symptoms included malaise (57 percent), cough (44 percent) and shortness of breath (51 percent).
- Interestingly, respiratory symptoms were not seen in up to 13 percent of patients. The physical exam was unrevealing, except for crackles on auscultation in 20 percent of patients and confusion in 1 percent.
- On laboratory findings, 73 percent of patients had lymphopenia, 60 percent had hyponatremia, and 50 percent had thrombocytopenia.
- C-reactive protein was elevated in 75 percent of patients.
- On admission, nearly all patients (96 percent) had pneumonic changes similar to those seen in community-acquired pneumonia. The 4 percent of patients with normal X-ray findings were found to have lung abnormalities (patchy opacification) via CT imaging.
Dr. Kettering noted that in the 32 patients who died within three months of contracting SARS, predictors of mortality were age (greater than 60 years) and an LDH level greater than 3.8ukat/L. She added that all patients who died experienced respiratory failure, and 44 percent had acute renal failure.
Bonnie Darves is a freelance writer specializing in health care. She is based in Lake Oswego, Ore.