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Neuromuscular Weakness After ARDS
Abstract & Commentary
By Saadia R. Akhtar, MD, MSc, Idaho Pulmonary Associates, Boise, is Associate Editor for Critical Care Alert.
Dr. Akhtar reports no financial relationship to this field of study.
Synopsis: This secondary analysis of a prior prospective randomized controlled trial of methylprednisolone vs placebo for persistent ARDS reveals that although ICU-acquired neuromyopathy is common after ARDS, and associated with worse clinical outcomes, methylprednisolone use does not appear to increase the risk.
Source: Hough CL, et al. Intensive care unit-acquired neuromyopathy and corticosteroids in survivors of persistent ARDS. Intensive Care Med 2009;35:63-68.
Hough et al set out to determine incidence and outcomes of early neuromyopathy in patients with persistent acute respiratory distress syndrome (ARDS), and to evaluate the association of neuromyopathy with the use of methylprednisolone in this population. To achieve this aim, they undertook a secondary analysis of a prospective randomized controlled trial of methylprednisolone in late ARDS (LaSRS).1
Twenty-five ICUs took part in LaSRS. Eligible patients were > 18 years old and at day 7-28 after the onset of ARDS. Enrolled subjects received methylprednisolone or equivalent placebo as follows: 2 mg/kg IV bolus, then 0.5 mg/kg every 6 hours for 14 days, then 0.5 mg/kg every 12 hours for 7 days, then tapered off over 2-4 days. Chart abstraction was used for data collection; neuromyopathy was identified by notation of "myopathy," "neuropathy," "myositis," "paralysis," or "unexplained muscle weakness." For this secondary analysis, Hough et al evaluated early neuromyopathy, defined as the above findings detected within the first 28 days of entry into LaSRS. The other eligibility criterion was survival to 60 days after enrollment or to hospital discharge. Patients with neuromyopathy prior to admission or entry into LaSRS were excluded for the analysis of association between methylprednisolone and neuromyopathy.
Of 180 patients in LaSRS, 128 (63 in treatment group; 65 in placebo group) were eligible for this analysis. Forty-three (34%) of these patients had neuromyopathy. (Interestingly, only 8 were reported as serious adverse events of neuromyopathy for LaSRS.) Compared to those without neuromyopathy, these 43 subjects had higher serum glucose levels and a trend towards worse oxygenation. They also had longer duration of mechanical ventilation (17 vs 11 days), higher likelihood of re-intubation (23% vs 10%), and longer time to return home (56 vs 34.5 days). After excluding the 6 patients with neuromyopathy present prior to enrollment in LaSRS, the authors found no increased risk of neuromyopathy in the methylprednisolone group (odds ratio, 1.5; 95% confidence interval, 0.7-3.2).
It is clear that neuromuscular weakness of some sort is a fairly common problem for critically ill patients (with or without ARDS) and may persist for months or longer following the initial ICU stay. A variety of associations has been identified in prior studies.2,3 However, much remains unknown about this complication. Is it one single entity? How can we more clearly define this (these) condition(s)? What is the true incidence? What are actual causal factors vs associations? What physiological and/or biochemical mechanisms underlie neuromyopathy in critical illness? How can risk be predicted? What simple screening tools can be devised? How can risk be reduced?
Hough et al's work reaffirms the relatively high incidence of neuromyopathy in critically ill patients. It also re-demonstrates interesting associations between neuromyopathy and certain predisposing factors (such as hyperglycemia), and also between neuromyopathy and outcomes (duration of ventilation, for example).
The lack of association between methylprednisolone and neuromyopathy in this analysis is surprising. That may be a reflection of the limitations of the study. First, the relatively small sample size restricts the statistical power to detect differences in outcomes between the study and placebo group. Second, reliance on chart notations regarding weakness makes it likely that case definition is incomplete and imprecise; a significant number of cases may be missed, thus the incidence and associations reported may be inaccurate. Alternatively, the lack of association could be explained by as-yet-unknown dose- or population-dependent effects of methylprednisolone on the development of neuromyopathy.
Although this study by Hough and colleagues may not provide a great deal of new information, its value lies in adding further observational data to the current scant body of knowledge, raising some new questions, and keeping the critical care community's attention on this important and complex topic so that we may continue to consider and investigate it.