Is Less Really More? Neuromuscular blockers in Early Acute Respiratory Distress Syndrome

Published - Written by Dominique Bayard

In March of 2010, during an overnight shift in the medical intensive care unit, I was paged to rush to the bedside of a patient being wheeled in with rapidly worsening hypoxemic respiratory failure. The patient was quickly intubated, yet still difficult to oxygenate. The X-ray showed bilateral, patchy infiltrates. Once it was determined these were not due to cardiogenic pulmonary edema – it hit me: Acute Respiratory Distress Syndrome (ARDS). Immediately, I switched the ventilator to low-lung-volume ventilation and increased sedation aggressively with the goal of eliminating all patient resistance to the ventilator. Despite high doses of numerous sedative infusions, the patient continued “bucking the vent.” I paused to consider, “Should I paralyze the patient?” The response to this difficult question varies widely from doctor to doctor.

For over 50 years, the medical literature has described clinical cases of Acute Respiratory Distress Syndrome, however it was not until 1994 that the American-European Consensus Conference on ARDS developed a standard definition:

  • Acute onset, bilateral infiltrates on chest radiography,
  • Pulmonary-artery wedge pressure of < 19 mm Hg or the absence of clinical
    evidence of left atrial hypertension, and
  • A ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2:FiO2 200.)

Currently, it is estimated that ARDS occurs in 150,000 patients a year. Despite extensive research, the mortality rate remains high, on the order of 40%. Aside from low-lung-volume ventilation, there is little evidence for other protective therapies, and there is no known pharmacologic therapy that reduces mortality.

In this week’s NEJM, Dr. Laurent Papazian et al. present a randomized, multicenter, double blind, placebo-controlled trial that investigated whether paralyzing a patient early in the course of severe ARDS improves clinical outcomes. Three hundred and forty patients presenting to the intensive care unit with acute onset of ARDS were randomized to receive cisatracurium besylate or placebo for 48 hours.

Jeffrey Drazen, editor-in-chief of the NEJM, and a pulmonary and critical care specialist, commented on why this particular therapy is of interest.

“ARDS is very common and often difficult to treat at the beginning of a patient’s illness,” says Dr. Drazen. “Upon intubation, getting the patient to synchronize with the ventilator is often a challenge. This dyssynchrony may cause barotrauma and suboptimal ventilation, which in turn may contribute to the patient doing poorly.”

In Papazian’s analysis, the study sample was not large enough to detect a statistically significant difference between the crude 90-day mortality rate of the cisatracurium goup and the placebo group. However, when the results were adjusted for the pre-specified covariates of baseline PaO2:FiO2, Simplified Acute Physiology II score, and plateau pressure, an intriguing finding emerged. In patients with a PaO2:FiO2 of less than 120, the mortality rate was 30.8% in the cisatracurium group versus 44.6% in the control group (P=0.04) – a 30% mortality rate reduction. Additionally, the cisatracurium group had more ventilator-free days and no increased incidence of ICU-acquired paresis.

In Dr. Arthur Slutsky’s editorial, he notes the potential paradigm shift that this article could bring from our present “less-is-more” attitude towards critical care: less ventilation to avoid ventilator induced lung injury, fewer blood transfusions, less sedation. Even the practice of rigorous blood sugar control in critically ill patients is now debated. Slutsky speculates on various potential mechanisms that may explain the benefit of neuromuscular blockade, but feels that more evidence will be needed to substantiate the alluring idea of having a pharmacologic intervention for patients with ARDS.

As with several other therapies – such as prone positioning, high oscillation ventilation, and extracorporeal ventilation – that are variably used in ARDS, more studies will be needed to determine if the use of cisatracurium and other neuromuscular blockers can reliably provide a benefit to ARDS patients. In the meanwhile, we are left with the ongoing question: Aside from low lung volume ventilation, what more can we consistently do for ARDS patients to lessen the dramatically high mortality rate?