Systemic corticosteroids have been studied extensively for use in ARDS. While they clearly have a role in situations when ARDS has been precipitated by a steroid-responsive process (eg, acute eosinophilic pneumonia), the value of steroids in most cases is uncertain.
Empiric corticosteroids were widely used to treat ARDS in the 1970s and early 1980s. However, corticosteroid therapy became less frequent in the late 1980s after several studies found that corticosteroids had no benefit and may cause harm in patients with ARDS.
The first clinical trial to report a beneficial effect of corticosteroids in ARDS was the one by Meduri et al in 1998. In a randomized, placebo controlled cross over single centre trial enrolling 24 patients corticosteroids were shown to improve lung injury score and reduce mortility.
Subsequent studies focused on patients in the fibroproliferative phase of ARDS, occasionally referred to as persistent ARDS or late ARDS. The fibroproliferative phase is characterized by fever, purulent secretions, and new pulmonary infiltrates without evidence of infection. Evidence that corticosteroids can ameliorate pulmonary inflammation has provided an important rationale for continuing to study their use in the treatment of ARDS.
A double-blind trial by the ARDS Network randomly assigned 180 patients with persistent ARDS to receive methylprednisolone or placebo for 21 days [NEJM 2006]. Persistent ARDS was defined as ongoing disease seven to 28 days after its onset. When the methylprednisolone and placebo groups were compared:
1. There was no difference in 60-day mortality (29.2 versus 28.6 percent) or 180-day mortality (31.5 versus 31.9 percent).
2. Among patients randomized 7 to 13 days after the onset of ARDS, methylprednisolone caused a nonstatistically significant reduction in 60-day mortality (27 versus 36 percent) and 180-day mortality (27 versus 39 percent).
3. Among patients randomized more than 14 days after the onset of ARDS, methylprednisolone increased 60-day mortality (35 versus 8 percent) and 180-day mortality (44 versus 12 percent).
4. methylprednisolone increased ventilator-free days, shock-free days, oxygenation, lung compliance, and blood pressure, but increased neuromuscular weakness and higher rate of reintubations.
Other clinical trials addressed the possibility that corticosteroids might be effective when given early in ARDS. In a double-blind trial, patients with early ARDS (ie, ≤72 hours) were randomly assigned in a 2:1 ratio to receive corticosteroid therapy (n=63) or placebo (n=28) [Meduri Chest 2007]. Patients failing in one arm by day 7 to 9 underwent blinded crossover. Patients in the corticosteroid group were given methylprednisolone at 1 mg/kg per day for up to 28 days. Important features of this trial included vigilant surveillance for infection and avoidance of neuromuscular blockade.
Corticosteroid therapy reduced the duration of mechanical ventilation, length of ICU stay, and ICU mortality (21 versus 43 percent). The results of this study should be considered provocative but not definitive given the trial's small size and imbalances in the treatment arms, which included a larger number of patients with catecholamine-dependent shock in the placebo group.
Several meta-analyses and reviews offer conflicting perspectives regarding corticosteroid treatment for ARDS.
Points of debate include when to begin steroids, how long to give them, whether they should be tapered, and how to interpret subgroup analyses in published trials. Although some data suggest possible survival advantages when given early, particularly before two weeks have elapsed, ongoing controversy dictates the need for more research before definitive recommendations regarding corticosteroids can be made.
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