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(Chest. 2001;120:464S-468S.)
© 2001 American College of Chest Physicians

Trials of Corticosteroids to Prevent Postextubation Airway Complications*

Maureen O. Meade, MD; Gordon H. Guyatt, MD; Deborah J. Cook, MD; T. Sinuff, MD and R. Butler, MD

* From the Departments of Medicine (Drs. Meade, Guyatt, Cook, and Sinuff), McMaster University, Hamilton, Ontario, Canada; and the Department of Anesthesia (Dr. Butler), University of Western Ontario, London, Ontario, Canada.

Correspondence to: Deborah J. Cook, MD, McMaster University, Faculty of Health Sciences Center, Department of Clinical Epidemiology, 1200 Main St West, Hamilton, Ontario, Canada: e-mail: debcook{at}mcmaster.ca


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
We identified three randomized controlled trials (RCTs) that addressed whether preextubation steroid administration reduces postextubation complications in children. The pooled analysis of primary extubation in children demonstrated significantly less stridor (relative risk [RR], 0.57; 95% confidence interval [CI], 0.40 to 0.81) and a trend toward less reintubation (RR, 0.50; 95% CI, 0.02 to 13.87) with corticosteroids. One non-RCT in children who had failed extubation the first time found a significant reduction in duration of prolonged reintubation (>= 6 days) and in failed reextubations. The four RCTs in adults reported very low reintubation rates, and no conclusions can be drawn. Only one RCT assessed postextubation stridor and found little difference. Overall, we found that corticosteroids decreased the risk of postextubation stridor in children by about 40%. However, the effect of corticosteroids in children and adults to reduce postextubation complications such as reintubation is uncertain.

Key Words: corticosteroids • extubation • mechanical ventilation • meta-analysis • reintubation • stridor • systematic reviews • weaning


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Laryngeal edema, and the resultant stridor, are common problems in children following tracheal extubation after mechanical ventilation.1 2 Not infrequently, airway compromise necessitates endotracheal reintubation. This sequence of events also occurs in adults, although far less often.3

Preextubation corticosteroid administration might, in theory, ameliorate this problem. The anti-inflammatory effect of corticosteroids could prevent or attenuate the degree of laryngeal edema. In cases that might otherwise be mild, corticosteroids might even eliminate significant edema. However, it is plausible that corticosteroid therapy might have insufficient time to act to prevent laryngeal edema or might, for a variety of other reasons, have a minimal therapeutic impact. Randomized controlled trials (RCTs) represent the only way to definitively resolve this issue, focusing on outcomes of importance to patients. In this section, we review the trials that investigators have conducted in both pediatric and adult populations.


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
We have described the methods of our systematic reviews in detail in the introduction to this supplement and in the article concerning alternative discontinuation assessment and weaning mode methods. Herein, we summarize these methods briefly, focusing on aspects specific to this topic.

Eligibility Criteria
We included all studies of adult and pediatric patients who had received mechanical ventilation that compared corticosteroid therapy to placebo therapy or control subjects and that measured at least one outcome related to upper airway complications. We included RCTs and controlled nonrandomized studies.

Search for Relevant Studies
To identify relevant studies, we searched MEDLINE, EMBASE, HEALTHStar, CINAHL, the Cochrane Controlled Trials Registry, and the Cochrane Data Base of Systematic Reviews from 1971 to September 1999, and we examined the reference lists of all included articles for other potentially relevant citations.

Data Abstraction and Assessment of Methodological Quality
Data abstraction and methodological quality rating were done in duplicate by one of five respiratory therapists and five intensivists. One of the investigators rechecked the final data abstraction.

The methodological features of RCTs that we abstracted included the following: the method of randomization and whether randomization was concealed; the criteria for weaning, extubation, and reintubation; the extent to which groups were similar with respect to important prognostic factors; whether investigators conducted an intention-to-treat analysis; whether patients, clinicians, and those assessing outcome were blind to allocation; the extent to which the groups received similar cointerventions; and the reporting of the reasons for study withdrawal.

For non-RCTs, we considered the extent to which groups were similar with respect to important prognostic factors, whether the investigators adjusted for differences in prognostic factors, and the extent to which the groups received similar cointerventions.

Statistical Analysis
We abstracted or, when necessary, calculated effect sizes in terms of relative risks (RRs) and associated 95% confidence intervals (CIs) for binary outcomes. We calculated mean differences and 95% CIs for continuous variables.

We pooled data when, in our judgment, the underlying pathophysiology was such that across the range of populations, management strategies in treatment and control groups, and the key outcomes studied we would expect more or less the same treatment effect. For instances in which we could pool continuous variables, we considered the mean in each group and an estimate of variability from each group that determined the weight given to the study in the pooled analysis. For pooling binary data, we calculated risk ratios using the methods described by Fleiss.4


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
We identified three RCTs5 6 7 that had addressed whether preextubation steroid administration can reduce postextubation stridor and the necessity for reintubation in children (Table 1 ). In all three studies, patients, caregivers, and those assessing outcome were blind to allocation, with patients having received dexamethasone or a matched placebo. Two trials5 6 (sample sizes, 66 and 153 children) enrolled patients who had not previously been extubated. A smaller trial7 enrolled 23 children who had been reintubated for postextubation stridor, who received two doses of dexamethasone or placebo 6 h before extubation, at extubation, then 6 and 12 h postextubation.


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  		Table 1. Characteristics of Randomized Trials of Corticosteroids to Prevent Postextubation Airway Complications*

 
Both of the trials of primary extubation examined both stridor scores and reintubation (Table 2 ). Early stridor was present more frequently in both trials in the group that did not receive steroids, and the differences persisted until 12 h in the one trial6 that measured stridor sequentially (Table 2) . Reintubation occurred more frequently in the steroid group in one study,5 and more frequently in the placebo group in the other study.6 In the trial of secondary extubation,7 the stridor score was slightly and not significantly higher (that is, worse stridor) in the placebo group, which also had a higher incidence of reintubation (5 of 11 vs 3 of 12 reintubations). This difference did not approach statistical significance.


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  		Table 2. Results of Individual RCTs of Corticosteroids to Prevent Postextubation Airway Complications*

 
One non-RCT8 evaluated the use of corticosteroid therapy to prevent postextubation airway complications in children. In this study, which evaluated steroid therapy in patients who had failed extubation the first time, Freezer et al8 reported a statistically significant reduction in prolonged reintubation (>= 6 days) and in failed reextubations.

The pooled analyses of the two RCTs of primary extubation demonstrated a substantial reduction in the frequency of stridor with a relatively narrow 95% CI (RR, 0.57; 95% CI, 0.40 to 0.81) (Table 3 ). The pooled analysis also suggested a reduction in reintubation with steroid therapy, but, in part because of the trends in different directions in the two studies, the 95% CI is extremely wide (RR, 0.50; 95% CI, 0.02 to 13.87) (Table 3) .


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  		Table 3. Pooled Results of Randomized Trials of Corticosteroids to Prevent Postextubation Airway Complications

 
The four trials9 10 11 12 of steroids in adult patients (Table 1) used different medications (ie, methylprednisolone, dexamethasone, and hydrocortisone)3 10 11 12 and were placebo-controlled. Only one of the studies11 assessed postextubation stridor, and it found little difference between the two groups (Table 2) . The need for reintubation was very infrequent in all four studies. As a result, even the pooled analysis demonstrates extremely wide 95% CIs around the pooled estimate of steroid impact on reintubation (Table 3) .


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Two well-designed trials5 6 of dexamethasone therapy prior to extubation in children have unequivocally demonstrated that steroids reduce postextubation stridor. The inferences from these trials are strengthened because patients, caregivers, and those assessing outcome were all blind to allocation. In contrast to the effect on stridor, the effect on reintubation is far from clear. In one of the two studies, 7 of 32 patients not receiving steroids required reintubation in contrast to 0 of 31 patients receiving steroids. The trend in the other study was in the opposite direction, with 4 of 77 not receiving steroids and 9 of 76 children receiving steroids requiring reintubation. We found no adequate explanation for this difference.

The three trials of steroid therapy in adults observed so few events that even the results of the pooled analysis have such wide 95% CIs that they are essentially uninformative. The results are consistent with a reduction in the RR of reintubation of 86%, and also with an increase in the RR of reintubation of 58%.

For clinicians who believe that preventing stridor in children after extubation is in itself important, the results of two RCTs provide a definitive answer. Steroids reduce the RR of stridor by > 40%. Even using the more conservative estimate of 21% stridor frequency in patients not receiving steroids, the results suggest that one needs to treat no more than 12 children with dexamethasone therapy to prevent one from developing stridor.

For those who believe that dexamethasone therapy is warranted only if it prevents reintubation, the question remains unanswered. Both trials6 7 found reintubation rates of > 10%. Although hundreds of children would ultimately have to be enrolled in RCTs to answer the question, it may well be worth investing the resources to resolve the issue.

In adults, the situation is different. Reintubation for upper airway obstruction is very infrequent.13 Tens of thousands of patients would have to be randomized to detect the absolute differences in effect that could be expected even if steroids substantially reduce the RR of laryngeal edema. Such a trial is almost certainly not worth the resources required. Focusing on a high-risk population, such as patients who have had airway trauma or those undergoing facial reconstruction, may be more fruitful and feasible.

The data included in this systematic review and a more comprehensive discussion of the original articles are included in an Evidence Report of the Agency for Healthcare Research and Quality.14


   Footnotes
 
Abbreviations: CI = confidence interval; RCT = randomized controlled trial; RR = relative risk

This article is based on work performed by the McMaster University Evidence-based Practice Center, under contract to the Agency for Healthcare Research and Quality (Contract No. 290-97-0017), Rockville, MD.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Deakers, TW, Reynolds, G, Stretton, M, et al (1994) Cuffed endotracheal tubes in pediatric intensive care. J Pediatr 125,57-62[CrossRef][ISI][Medline]
  2. Kemper, KJ, Benson, MS, Bishop, MJ (1991) Predictors of postextubation stridor in pediatric trauma patients. Crit Care Med 19,352-355[Medline]
  3. Miller, RL, Cole, RP (1996) Association between reduced cuff leak volume and postextubation stridor. Chest 110,1035-1040[Abstract/Free Full Text]
  4. Fleiss, J (1993) The statistical basis of meta-analysis. Stat Methods Med Res 2,121-145[Medline]
  5. Tellez, DW, Galvis, AG, Storgion, SA, et al (1991) Dexamethasone in the prevention of postextubation stridor in children. J Pediatr 118,289-294[Medline]
  6. Anene, O, Meert, KL, Uy, H, et al (1996) Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial. Crit Care Med 24,1666-1669[CrossRef][ISI][Medline]
  7. Harel, Y, Vardi, A, Quigley, R, et al (1997) Extubation failure due to post-extubation stridor is better correlated with neurologic impairment than with upper airway lesions in critically ill pediatric patients. Int J Pediatr Otorhinolaryngol 39,147-158[CrossRef][Medline]
  8. Freezer, N, Butt, W, Phelan, P (1990) Steroids in croup: do they increase the incidence of successful extubation? Anesth Intensive Care 18,224-228[Medline]
  9. Gaussorgues, P, Boyer, F, Piperno, D, et al (1987) Laryngeal. edema after extubation: do corticosteroids play a role in its prevention? Presse Med 16,1531-1532
  10. Darmon, JY, Rauss, A, Dreyfuss, D, et al (1992) Evaluation of risk factors for laryngeal edema after tracheal extubation in adultsand its prevention by dexamethasone: a placebo-controlled, double-blind, multicenter study. Anesthesiology 77,245-251[CrossRef][ISI][Medline]
  11. Ho, LI, Harn, HJ, Lien, TC, et al (1996) Postextubation laryngeal edema in adults: risk factor evaluation and prevention by hydrocortisone. Intensive Care Med 22,933-936[ISI][Medline]
  12. Chaney, MA, Nikolov, MP, Blakeman, B, et al (1998) Pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting and early tracheal extubation. Anesth Analg 87,27-33[Abstract/Free Full Text]
  13. Epstein, SK, Ciubotaru, RL (1998) Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. Am J Respir Crit Care Med 158,489-493[Abstract/Free Full Text]
  14. Criteria for Weaning From Mechanical Ventilation. Evidence Report/Technology Assessment No. 23 from the Agency for Healthcare Research and Quality: AHRQ Publication No. 01-E010



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This Article
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