ABSTRACT & COMMENTARY
To Improve Outcomes in AECOPD, Go Easy on the Steroids!
By David J. Pierson, MD, Editor
SYNOPSIS: In this examination of outcomes among 17,239 patients admitted to the ICU for an acute exacerbation of COPD, most of them received higher than recommended doses of corticosteroids (> 240 mg/d methylprednisolone equivalent). Patients treated with higher-dose steroids had longer lengths of stay, higher costs, and more steroid-associated adverse effects, with no evidence for added benefits in comparison with those who received lower doses.
Kiser TH, et al. Outcomes associated with corticosteroid dosage in critically ill patients with acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2014;189:1052-1064.
Corticosteroids are beneficial in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). It can be assumed that patients with AECOPD who are admitted to the ICU are sicker than similar patients managed on the general wards, and given that more seriously ill patients generally need more intensive therapy it seems natural to assume that higher steroid doses should be used in such patients. This study tests this assumption, using a large nationwide database by examining patient outcomes and resource use in relation to corticosteroid dosage in ICU patients with AECOPD.
In this pharmacoepidemiologic cohort study, Kiser and colleagues at the University of Colorado examined data on patients admitted to an ICU for AECOPD included in Premier Incorporated’s Perspective database covering a 6-year period from 2003 through 2008. Study patients entered the ICU on day 1 or 2 of admission and had corticosteroid treatment initiated within the first 2 days. Outcomes examined included hospital mortality, ICU length of stay, hospital length of stay, initiation and length of noninvasive ventilation, total hospital costs, readmission for AECOPD within 30 days, and other measures of management and outcome. Adverse events potentially related to corticosteroid administration were examined, including hyperglycemia, need for insulin therapy, gastrointestinal bleed, critical illness polyneuropathy, fungal infection, and antifungal therapy. The patients were divided into two groups based on commonly used corticosteroid dosing regimens: 240 mg methylprednisolone equivalent (e.g., 60 mg every 6 h) or less and higher doses (e.g., 125 mg every 6 h, or more) during the first 2 days of treatment.
A total of 17,239 patients from 473 hospitals were included. A total of 6156 (36%) patients received lower-dose corticosteroids and 11,083 (64%) received higher doses. Thirty-two percent of the patients received noninvasive ventilation, 15% received invasive mechanical ventilation, and 89% were treated with antibiotics. Most patients were given the corticosteroids (generally methylprednisolone) parenterally, while only 3.9% received oral prednisone. Overall mortality was 5.3% in the low-dose group vs 6.3% in the high-dose group (P = 0.04), but propensity matching and adjustment for regional differences in management eliminated this significant difference (odds ratio, 0.85; 95% confidence interval [CI], 0.71-1.01; P = 0.06). However, lower-dose corticosteroids were significantly associated with shorter ICU (-0.31 d; 95%CI, -0.46 to -0.16; P < 0.01) and hospital (-0.44 d; 95%CI, 0.67 to -0.21; P < 0.01) lengths of stay, as well as lower hospital costs (-$2559; 95%CI, -$4508 to -$609; P = 0.01) and significantly less need for insulin therapy and fungus infections (both, P < 0.01). There were no other significant outcome associations. Thus, patients treated with higher-dose steroids had longer lengths of stay, higher costs, and more steroid-associated adverse effects, with no evidence for added benefits in comparison with those lower doses.
COMMENTARY
This was not a clinical trial prospectively examining the effects of higher- vs lower-dose corticosteroids in ICU patients with AECOPD, treated in the same units by the same clinicians with the dosage difference being the only variable. It is pretty unlikely that such a trial will be done — particularly with anything like the numbers of patients included in this pharmacoeconomic cohort study — and this study’s results seem to me compelling enough for many intensivists to reevaluate their practice in managing this condition. The logical notion that if some corticosteroids are good for patients with AECOPD treated as outpatients or on the general wards, then those sick enough to be admitted to the ICU should be treated with substantially larger doses is refuted by this study. And bigger doses are not just wasteful of unnecessary medication, they are actually worse for the patient (more complications, longer stays) as well as for the health care system (longer stays, higher costs).
An interesting if not surprising finding of this study was that fewer than 1 in 20 patients with AECOPD were treated with oral prednisone as opposed to a parenteral steroid such as methylprednisolone. When COPD patients have exacerbations, we treat them with prednisone if they do not require hospitalization, but we nearly always use parenteral steroids when they have to be admitted. The latter is vastly more expensive and inconvenient, and it is not evidence-based in any but the most unusual circumstances. Prednisone’s bioavailability is such that, unless a patient is actively vomiting or on continuous gastric suction, it is essentially completely absorbed, even in critical illness. A recent, very large study of patients hospitalized with AECOPD (but not admitted to the ICU) found no evidence for any worse outcome among those treated with oral prednisone as compared to parenteral corticosteroids, even after extensive statistical manipulations to eliminate confounding variables such as underlying COPD severity or severity of the acute episode.1
REFERENCE
- Lindenauer PK, et al. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA 2010;303:2359-2367.
