This NMA indicated the necessity of administering steroids in multiple doses or in a single dose to prevent the risk of reintubation after extubation in critically ill patients, and assessed the outcome-specific certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system compared with previous meta-analysis. The pairwise meta-analysis showed that there was no significant difference between multiple doses and single-dose steroids in terms of reducing the risk of reintubation; however, the NMA showed that the use of a single dose was statistically superior to the use of multiple doses. Additionally, both multiple doses and single-dose steroids have shown significant superiority in lowering the reintubation rate compared with placebo in several studies.
The results of this study were inconsistent with those of previous studies, which reported that multiple doses are more effective than single-dose steroids4,9. The duration of action of steroids is at least 8 hours; MP, an intermediate-acting steroid, 12–36 hours; and DM, a long-acting steroid, 36–72 hours18. In the included studies, multiple doses were administered every 4–6 hours. Considering the decrease in body distribution over time and the increase of drug concentration in the blood, multiple doses are a relatively high dose, and the duration of action is longer than that of a single dose. However, the evidence that multiple doses of steroids can lower reintubation than single doses remained unclear. The dosage of steroids and duration of use are important independent risk factors for the occurrence of side effects19. If multiple doses of steroids do not significantly lower the occurrence of reintubation compared with a single dose, this dosing method should not be used as it is cumbersome, is time consuming, and requires more manpower.
The steroids used before extubation are short acting and are administered in smaller doses; to date, no study has reported the direct side effects of steroid use during extubation. Even if side effects occur, they are reversible and more likely to be the effect of prolonged use of steroids in critically ill patients rather than the side effect of the use of prophylactic steroids. Therefore, clinicians might consider the use of steroids to prevent the occurrence of complications after extubation based on the patient’s condition and environment.
The last study included in the analysis was conducted in 20169; no RCT has reported the use of steroids to prevent reintubation after extubation. In recent years, noninvasive ventilation (NIV) and high-flow oxygen therapy (HFOT) after extubation to prevent reintubation are used as alternative respiratory supports20–22. The latest NMA reported that NIV is the most effective respiratory support method for preventing reintubation after extubation23. None of the studies included in this meta-analysis used alternative respiratory support after extubation. Steroids used prior to planned extubation and NIV and HFOT used after extubation are not opposite treatments. Although no previous RCTs have used steroids and alternative respiratory support sequentially, these treatment methods can prevent the incidence of reintubation; however, further research is needed to confirm this finding.
This study has several limitations. First, the use of three types of steroids can cause bias. Although a standard steroid dose equivalent to the HC dose has been established to achieve the relative anti-inflammatory effect, the interpretation of results is limited due to the differences in the duration of action, time of onset, and duration of potency for each steroid. Second, a slightly direct comparison was performed between multiple doses and single dose. In the network statistics, statistical analysis was performed by adding the values of direct and indirect comparisons; statistically, the consistency was satisfied in this study. However, due to the small number of studies, the results cannot be considered as clinically significant. Hence, additional NMA should be conducted in future studies. Third, the included studies were conducted in China and Taiwan, except for one study, and the generalizability of the results was limited because the studies were only focused on a certain ethnic group and regional area.
In conclusion, this NMA showed that multiple doses of prophylactic steroids were not statistically superior to single-dose steroids in reducing the incidence of reintubation after extubation among critically ill patients, and a single dose of steroid might be sufficient to reduce the incidence of reintubation. In addition, both methods are more effective than placebo. Although multiple doses of steroids can increase the steroid concentration and retention time in blood, its effect in preventing reintubation is not superior to that of a single dose. Therefore, a single dose can be used to reduce the rate of reintubation.