Effects of steroids on reintubation and post-extubation stridor in adults: meta-analysis of randomised controlled trials

Abstract

Introduction: The efficacy of steroid administration before planned tracheal extubation in critical care patients remains controversial with respect to the selection of patients most likely to benefit from this treatment.

Methods: We performed an extensive literature search for adult trials testing steroids versus placebo to prevent reintubation or laryngeal dyspnoea. Studies were evaluated on a five-point scale based on randomisation, double-blinding and follow-up. Our analysis included trials having a score three or higher with patients mechanically ventilated for at least 24 hours and treated with steroids before extubation, taking into account the time of their administration (early vs late) and if the population selected was at risk or not.

Results: Seven prospective, randomised, double-blinded trials, including 1846 patients, (949 of which received steroids) were selected. Overall, steroids significantly decreased the risk of reintubation (relative risk (RR) = 0.58, 95% confidence interval (CI) = 0.41 to 0.81; number-needed-to-treat (NNT) = 28, 95% CI = 20 to 61) and stridor (RR = 0.48, 95% CI = 0.26 to 0.87; NNT = 11, 95% CI = 8 to 42). The effect of steroids on reintubation and stridor was more pronounced for selected high-risk patients, as determined by a reduced cuff leak volume (RR = 0.38, 95% CI = 0.21 to 0.72; NNT = 9, 95% CI = 7 to 19; and RR = 0.40, 95% CI = 0.25 to 0.63; NNT = 5, 95% CI = 4 to 8, respectively). In contrast, steroid benefit was unclear when trials did not select patients for their risk of reintubation (RR = 0.67, 95% CI = 0.45 to 1.00; NNT = 44, 95% CI >/= 26 to infinity) or stridor (RR = 0.56, 95% CI = 0.20 to 1.55).

Conclusions: The efficacy of steroids to prevent stridor and reintubation was only observed in a high-risk population, as identified by the cuff-leak test and when it was administered at least four hours before extubation. The benefit of steroids remains unclear when patients at high risk are not selected.

Figure 1

Flowchart of randomised controlled trials selected for the meta-analysis. ARDS = acute respiratory distress syndrome.

Figure 2

Risk of reintubation according to the studied population. Risk ratio of reintubation rate for the individual randomised controlled trials comparing steroids with control groups. Vertical line = 'no difference' point between the two groups; squares = risk ratios (the size of each square denotes the proportion of information given by each trial); diamonds = pooled risk ratios for randomised controlled trials that did not select patients at high risk (upper) and trials that did select patients at high risk, based on a reduced cuff-leak volume (CLV; lower); horizontal lines = 95% confidence intervals (CI).

Figure 3

Risk ratio for post-extubation stridor according to the studied population. Risk ratios of post-extubation stridor rate for the individual randomised controlled trials comparing steroids with control groups and the pooled analysis. Vertical line = 'no difference' point between the two groups; squares = risk ratios (the size of each square denotes the proportion of information given by each trial); diamonds = pooled odds ratios for randomised controlled trials that did not select patients at high risk (upper) and trials that did selected patients at high risk, based on a reduced cuff leak volume (CLV; lower); horizontal lines = 95% confidence intervals (CI).

Figure 4

Funnel plot for outcome reintubation to detect bias or systematic heterogeneity in trials according to the studied population (selected vs unselected patients at risk based on a reduced cuff-leak volume). Each point represents one trial. SE = Standard Error. RR = Relative Risk.

Figure 5

Risk for reintubation according to the steroid administration initiation timing before extubation in unselected patients. Risk ratios of reintubation rate for the individual randomised controlled trials comparing steroids with control groups and the pooled analysis. Vertical line = 'no difference' point between the two groups; squares = odds ratios (the size of each square denotes the proportion of information given by each trial); diamonds = pooled odds ratios for randomised controlled trials with for which steroid administration was started less than two hours before planned extubation (upper) and trials for which steroid administration was started at least four hours (ranged 4 to 24 hours) before planned extubation (lower); horizontal lines = 95% confidence intervals (CI). CLV = cuff-leak volume.

Figure 6

Risk for post-extubation stridor according to the timing steroid administration initiation before extubation in unselected patients. Risk ratios of post-extubation stridor rate for the individual randomised controlled trials comparing steroids with control groups and the pooled analysis. Vertical line = 'no difference' point between the two groups; squares = odds ratios (the size of each square denotes the proportion of information given by each trial); diamonds = pooled odds ratios for randomized controlled trials for which steroid administration was started less than two hours before planned extubation (upper) and trials for which steroid administration was started at least four hours (ranged 4 to 24 hours) before planned extubation (lower); horizontal lines = 95% confidence intervals (CI). CLV = cuff-leak volume.