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ABSTRACT & COMMENTARY
By Linda L. Chlan, RN, PhD, FAAN
Dean’s Distinguished Professor of Symptom Management Research, The Ohio State University, College of Nursing
Dr. Chlan reports that she receives grant/research support from Hospira.
SYNOPSIS: Mean daily doses of up to 40 mg of prednisone equivalents and lengthy ICU stays were associated with impaired physical outcomes in patients who survived acute lung injury.
SOURCE: Needham D, et al. Risk factors for physical impairment after acute lung injury in a national, multicenter study. Am J Respir Crit Care Med 2014;189:1214-1224.
Patients with acute lung injury (ALI) who survive lengthy ICU stays are at risk for a plethora of adverse outcomes, including impaired and prolonged recovery of physical functioning. Many times, medications such as corticosteroids and neuromuscular blocking agents, administered to treat patients with ALI, contribute to these decrements. Needham et al sought to tease out the complex interplay of corticosteroids on patient outcomes and how that might influence any physical limitations in those patients who survived ALI. The purpose of this observational, secondary data analysis was to pool data from ALI patients from 12 hospital sites co-enrolled in two ARDSNet studies to evaluate 6- and 12-month physical outcomes and a number of risk factors in those who survived their ICU stays. Three physical outcomes measures were selected as markers of long-term outcomes from a list of seven measures included in the original data set: 1) manual muscle testing for extremity strength using the MRC sum score, 2) the 6-minute walk test (6MWT) for physical functioning, and 3) the SF-36 physical function (PF) scale as a measure of quality of life.
The study sample consisted of 203 ALI patients with a mean age of 48 (± 15) years, 49% male, and a mean APACHE III score of 85 ± 25. ALI patients received mechanical ventilation for a mean of 11 (± 9) days, had ICU stays of 14 (± 11) days, while 27% received neuromuscular blocking agents and 43% received corticosteroids, with a mean daily dose of the latter of 52 (± 81) mg (prednisone equivalents). At 6 months, 8% of patients had ICU-acquired weakness by the MRC sum score, with percent predicted values on the 6MWT of 65% (± 22) and 61% (± 36) on the SF-36PF. Between the 6- and 12-month assessment points, there were small improvements in the physical outcomes included in this study. Several multiple regression models were run, adjusting for age, gender, comorbidities, and baseline functional status.
The authors reported that corticosteroid dosages had a non-linear relationship to the three main outcomes of interest, with a change in slope occurring at a mean daily dose of 40 mg prednisone equivalents. Overall, corticosteroid doses up to 40 mg/day, prednisone equivalents, and ICU length of stay were significantly associated with decrements in the physical outcome measures. In patients who did not receive any corticosteroids, there was a significant decrement in all three of the physical measures of 1.33-4.59% in muscle strength, 6MWT, and SF-36PF. For each 10 mg/day increase in mean prednisone equivalents, up to 40 mg, there was a decrease in 6MWT and SF-36PF results. Interestingly, there were no significant changes in the physical measures for dose increases above 40 mg prednisone equivalents. To complicate the puzzling findings even further, an interaction between corticosteroid dose and ICU length of stay indicated that the corticosteroid prednisone equivalent doses had a negative effect on physical outcomes in those patients with a shorter ICU stay. The authors reported the results of several post hoc analyses that did not influence the main findings, including no impact of daily doses of sedative and opioid medications.
The findings from the observational study by Needham and colleagues provide more evidence of the decrements in physical outcomes in critically ill patients who experience lengthy ICU stays and mechanical ventilatory support due to ALI. However, the reader needs to keep in mind that association does not imply causation. Therefore, one cannot state that corticosteroids and lengthy ICU stays cause decrements in physical function.
The relationship between corticosteroid dose and physical function is complex. The investigators of this study posit that ICU-acquired weakness and other physical function decrements are so common among the critically ill with lengthy ICU stays that it may be difficult to detect any influences specially attributed just to the receipt of specific medications, such as corticosteroids. Similar to minimizing doses of sedative and opioid medications, a judicious approach may be warranted with the dosing and duration of corticosteroids used in the ICU. The findings from this study add more evidence to the detrimental influence of prolonged bed rest and immobility on the physical function of patients who survive ALI.