Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

Highlighted lines and questions below provide links to the pertinent description of criteria in The EBM User's Guide, now available at the Canadian Centres for Health Evidence

Article Reviewed:

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Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial.

Anene O, Meert KL, Uy H, Simpson P, Sarniak AP.

Crit Care Med 1996; 24: 1666-1669. [abstract]

Reviewed by Adrienne Randolph

Review posted April 20, 1997

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I. What is being studied?:

The study objective:

To determine whether dexamethasone prevents postextubation airway obstruction in young children.

The patients included:

66 children aged < 5 years, intubated for > 48 hours, upon first elective extubation, at the Children's Hospital of Michigan.

The patients excluded:

Patients admitted for laryngotracheal infections and those who received corticosteroids within 7 days before extubation.

The interventions compared:

Dexamethasone IV 0.5 mg/kg per dose (maximum 10 mg) or normal saline with the first dose 6 to 12 hours before extubation and subsequent doses every 6 hours for a total of six doses.

The outcomes evaluated:

Stridor, Croup Score, and pulsus paradoxus measurements at 10 minutes, 6, 12, and 24 hours after extubation; the need for aerosolized racemic epinephrine, helium-oxygen gas mixture, or reintubation.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes. Randomization was done using a random number table by a pharmacist not involved in patient care.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Not quite. Three patients were excluded after randomization from the final analysis; one with occult gastrointestinal bleeding (dexamethasone group) and two with hypertension (one from each group). The outcomes for these patients after extubation are not reported.

Were patients analyzed in the groups to which they were randomized?

Yes. No patients crossed over into the comparison group.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

Yes. The medications were prepared by the pharmacy and the study was double blind; neither the patients nor the providers knew if they received dexamethasone or placebo.

4. Were the groups similar at the start of the trial?

Almost. The two groups were similar in age, gestational age, presence of underlying airway anomalies, admitting diagnoses, duration of endotracheal intubation, endotracheal tube size, and use of sedation or paralysis. In the placebo group there were significantly more females and a trend towards more airway manipulations, usually consisting of exchanging the endotracheal tube from the oral to the nasal position. In the dexamethasone group, 21% of patients had one additional airway manipulation and 6% had two or more airway manipulations. In the placebo group, 33% of patients had one additional airway manipulation and 15% had two or more airway manipulations

5. Aside from the experimental intervention, were the groups treated equally?

Yes. Between trial entry and extubation the airway management was standardized with experienced operators and tube sizes chosen according to the published recommendations. Paralysis was used in patients requiring high airway pressures. Patients were electively extubated when they were able to maintain oxygenation on PEEP < 4 and FiO2 < 0.4. All patients received intravenous ranitidine.

III. What were the results?

1. How large was the treatment effect?

Dexamethasone decreased the frequency of upper airway obstruction requiring racemic epinephrine (Relative Risk 0.19; 95% CI 0.07, 0.48) and was associated with a decrease in the need for reintubation (Relative Risk 0.07; 95% CI 0, 1.15). Even when the patients undergoing more than one airway manipulation were excluded, there was still a reduced need for racemic epinephrine in the dexamethasone group (Relative Risk 0.14; 95% CI 0.04, 0.55) and a persistent trend towards decreased need for reintubation in the dexamethasone group (Relative Risk 0.16; 95% CI 0.01, 3.06).

At 10 minutes and 6 and 12 hours following extubation, treated patients exhibited significantly lower average croup scores and incidence of stridor. This analysis essentially withstood the exclusion of patients undergoing additional airway manipulations. Only patients with arterial lines had pulsus paradoxus evaluated; these were about one-third of all patients and there was also reduced pulsus paradoxus in the dexamethasone group.

2. How precise was the estimate of the treatment effect?

The confidence intervals (CI) reported above show that we can be 95% confident that the overall risk of reintubation with dexamethasone is between 100% (see footnote) better or 15% worse. After the patients with multiple intubations are excluded, the risk of reintubation could be reduced by 99% or increased 300%. Therefore, we can't be certain that dexamethasone reduces the need for reintubation. For use of racemic epinephrine, the confidence intervals do not cross one. We can be 95% sure that the usage of racemic epinephrine for upper airway obstruction in the dexamethasone group was at least cut in half.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

Yes. The patient population is representative of patients in many PICU's, although 50% of the patients were cardiac surgery patients and 10% had underlying airway anomalies. Management of the airway was done by experienced operators and endotracheal tubes sizes conformed to those recommended by published literature. However, if smaller endotracheal tubes are routinely used or if all patients are nasotracheally intubated, it is possible that the outcomes may differ and the incidence of significant postextubation stridor may be lower. It would be important to assess the baseline rate of postextubation strider necessitating use of racemic epinephrine and reintubation in an institution before routinely administering dexamethasone.

2. Were all clinically important outcomes considered?

Yes. Upper airway obstruction was assessed using clinical scores and the need for clinical interventions (reintubation and use of racemic epinephrine).

3. Are the likely treatment benefits worth the potential harms and costs?

Possibly. Dexamethasone is inexpensive relative to an extra day of intubation for upper airway obstruction due to edema. There were no significant differences in side effects (hypertension, hyperglycemia, and gastrointestinal bleeding) in the dexamethasone versus the placebo groups. However, these side effects of steroid use could not be adequately evaluated in this sample size. In 33 patients, the confidence interval for the apparently low rate of complications may be as high as 9% (See CI calculations).

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Related Reviews:

Tellez DW, Galvis AG, Storgion SA, Amer HN, Hoseyni M, Deakers TW. Dexamethasone in the prevention of postextubation stridor in children. J Pediatr 1991;118:289-294.

• Review, by A. Randolph

Harel Y, Vardi A, Quigley R, Brink LW, Manning SC, Carmody TJ, Levin DL. 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 Otorhynolaryngal 1997; 39: 147-158.

• Review, by B. Markovitz

Footnote: Correction

4/24/98: The original publication of this confidence interval interpretation was 93% better; with a lower CI of 0, the correct interpretation is 100% better. [return to text]

Comments

May 1, 1997

With respect to the two reviews on papers investigating post-extubation stridor: The review did not address the issue of assessing for ETT leak prior to inclusion in the randomization group. While neither showed tremendous benefit from the use of decadron, it appears to me that the study group was inappropriate. I would be more interested in seeing whether dex. relieves post-extubation stridor in patients whom you are reasonably sure will have it--ie, those who do not have a ETT leak at less than 20 cm H20. I am concerned that these two trials will lead to the assumption that dexamethasone is not useful in treating those those for whom it may actually be a benefit.

Laura Ibsen, MD (LIBSEN@chmca.org)
Children's Hospital Medical Center of Akron
Akron, Ohio

May 2, 1997

Some problems with the review:
RR values are EXTREMELY low, and indicate a marked preference for the better outcome. Were they calculated correctly?

Why were the patients with hypertension excluded from the analysis? What was the justification for excluding the patient with GI bleeding? The rationales were unclear in the abstract and the review.

Again, as with my previous critique, a more useful way of analyzing the data may be 1) logistic regression, using a dichotomous outcome (e.g. racemic epi yes/no, reintubation yes/no) or a polytomous outcome (e.g. croup score). In this way, one could calculate odds ratios and CI's for the odds ratios as well as adjusting for other independent variables. 2) Survival analysis as a means of determining if differences exist between the two groups say, in the rate of increase in croup score, or time to first racemic epi.

Finally, I've found the use of formal decision analytic techniques VERY helpful in eliciting the relative clinical values of different therapies, and certainly more useful than straight statistics in answering the question about usefulness in practice. The problem of the use of dexamethasone is a perfect one to which decision analysis can be applied.

Jay R. Shayevitz, MD (jayshay@umich.edu)
Providence Hospital and Medical Centers
Southfield, MI

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