Thursday, November 11, 2010

The use of neuromuscular blockers in ARDS---is the pendulum swinging back?

You're no doubt aware of the hype surrounding this issue as a result of a new NEJM study. From the study:

...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...

The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 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% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups.

In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness.

And how did they define severe ARDS?

Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. 

So this is a select group of patients among those presenting with ALI/ARDS. It's not for everyone. We haven't come full circle, back to the days when it seems we paralyzed nearly everyone.

There's some insightful discussion over at the NEJM blog. First, it must be recognized that it's difficult to ventilate patients on the ARDSnet protocol without heavy sedation, or, on occasion, paralysis. That's because ARDSnet tidal volumes don't satisfy the dyspnea of some patients. Aside from that, in other patients who matched the conditions of this study, the findings must be interpreted with caution. It must be kept in mind that there was a significant reduction in the adjusted, though not the crude 90 day mortality with the intervention. Further study may be warranted before we routinely change practice in patients, even those with a PO2/FiO2 of less than 150, who otherwise are “cruising” and able to tolerate ARDSnet tidal volumes with sedation alone.

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