January 2012 Critical Care Journal Club

Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guérin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107-16. (Click here for full text version of article)

We reviewed this “older” article to teach the fellows adjusted mortality and biological plausibility. In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment, adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval, 0.48 to 0.98; p=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% in the cisatracurium group and 40.7% in the placebo group (p=0.08). Mortality at 28 days was 23.7% with cisatracurium and 33.3% with placebo (p=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups.

The trial was well done but several issues were raised. The first was regarding p values. In this study p=0.08 for the unadjusted mortality but was p=0.04 when the adjusted mortality was calculated. Although it was thought to be reasonable to adjust the mortality based on predefined criteria, it was pointed out that there is nothing magic about a p value of 0.05 and these results are marginally significant. There was also a lack of biological plausibility, i.e., it is unclear why neuromuscular blockers should improve survival in ARDS. Although several explanations were offered, none were particularly convincing. Several minor issues were also raised which were summarized in the letters to the editor (NEJM 2010;363:2562-4) including whether the patients could be truly randomized. We discussed whether we should adopt neuromuscular blockers routinely in ARDS but most thought the evidence was sufficiently weak that watchful waiting pending a confirmatory trial was the best course.

Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF; LIFENOX Investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 2011;365:2463-72. (Click here for abstract)

Although thromboprophylaxis reduces the incidence of venous thromboembolism in acutely ill medical patients, a reduction in mortiality has not been shown. The authors conducted a double-blind, placebo-controlled, randomized trial to assess the effect of subcutaneous enoxaparin (40 mg daily) compared to placebo — both administered for 10±4 days in patients who were wearing elastic stockings with graduated compression — on the rate of death from any cause among hospitalized, acutely ill medical patients at participating sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia. The primary efficacy outcome was the rate of death from any cause at 30 days after randomization. The primary safety outcome was the rate of major bleeding during and up to 48 hours after the treatment period. A total of 8307 patients were randomly assigned to receive enoxaparin or placebo. The rate of death from any cause at day 30 was 4.9% in the enoxaparin group as compared with 4.8% in the placebo group (p= 0.83). There was also no difference in the rate of major bleeding, sudden Residents' suggestions for reducing errors in teaching hospitals. Enoxaparin was not associated with a reduction in the rate of death from any cause among hospitalized, acutely ill medical patients.

This article was chosen because it complements and supports the ACP thromboembolism prophylaxis guidelines which were reviewed in the December 2011 Critical Care Journal Club. These guidelines recommend assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism.

Volpp KG, Grande D. Residents' suggestions for reducing errors in teaching hospitals. N Engl J Med 2003;348:851-5. (No abstract or free full text available)

The Institute of Medicine’s 2000 report “To Err Is Human” precipitated a firestorm of publicity on the issue of medical errors which continues to this day. We reviewed this older article which described errors or situations identified by residents in a teaching hospital potentially leading to poor patient outcomes.

Table 1. Errors or situations predisposing to errors in teaching hospitals (Adapted from Volpp and Grande. N Engl J Med 2003;348:851-5).

1. Frequent interruptions with paging
2. Errors in orders and medical records
3. Errors in sign-out procedures
4. Excessive hours of work
5. Reluctance in reporting of errors
6. Poor training in procedures
7. Resident inability to act as a leader of a medical team

Although it is not clear from the article how the authors obtained the list of errors from the residents, most agreed that each of these can be a problem. However, it was unclear whether there was progress made in any of these areas other than reduction in work hours which may have led to increased errors in other areas.

Richard A. Robbins, MD

Editor, SWJPCC

Reference as: Robbins RA. January 2012 critical care journal club. Southwest J Pulm Crit Care 2012;4:22-3. (Click here for a PDF version of the journal club)