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

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Article Reviewed:

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Corticosteroids for the Prevention of Reintubation and Postextubation Stridor in Pediatric Patients: A Meta-Analysis.

Markovitz BP, Randolph AG.

Pediatr Crit Care Med 2002; 3:223-226. [abstract; full-text on Medscape]

Reviewed by Kevin Brinkman MD, University of Tennessee, Memphis, TN

Review posted March 14, 2003

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I. Are the results of the study valid?

A. Primary questions:

1. Did the overview address a focused clinical question?

Yes. There were 2 objectives of this analysis. The primary objective was to determine whether corticosteroids are effective in preventing or treating postextubation stridor and reducing the need for subsequent reintubation of the trachea in critically ill neonates, infants and children. The secondary objective was to determine the extent of detrimental effects of steroid therapy in this context.

2. Were the criteria used to select articles for inclusion appropriate?

Yes. The authors restricted their interests to randomized controlled trials comparing the administration of corticosteroids with placebo on the prevalence of reintubation or postextubation stridor in neonates, infants, or children receiving mechanical ventilation via an endotracheal tube in an intensive care unit. Patients with known tracheitis, laryngitis, laryngotracheobronchitis, or external or surgical trauma to the larynx or subglottis were excluded.

B. Secondary questions:

3. Is it unlikely that important, relevant studies were missed?

Yes. Controlled trials were identified through searches utilizing MEDLINE, EMBASE, CINAHL and the Cochrane Clinical Trials Registry. Authors of randomized controlled trials were also contacted to confirm methodology, provide additional data if necessary, and to request their identification of any unpublished or missed trials.

4. Was the validity of the included studies appraised?

Yes. (1) The allocation concealment was ranked using the Cochrane approach in which grade A represents adequate concealment, grade B is uncertain, and grade C is clearly inadequate concealment. One study (Tellez et al.) received grade B while the rest were grade A. (2) All studies were described as randomized, double-blind, with both appropriate descriptions of randomization and adequate descriptions of control treatment. (3) The likelihood of bias was assessed on a 5-point scale based on the approach of Jadad et al. The pediatric studies were rated as a score of 3 (Tellez et al.) and 5 (Anene et al. and Harel et al.). The neonatal studies were rated as a score of 4 (Couser et al.) and 5 (Ferrara et al. and Courtney et al.).

5. Were assessments of studies reproducible?

Yes. There was no disagreement between the two reviewers with respect to quality assessment done independently. After discussion, there was also no disagreement regarding data extraction. Some of the information detailing methods of concealment and randomization were only obtained after direct contact with authors.

6. Were the results similar from study to study?

No. The results of both the neonatal and pediatric studies demonstrated heterogeneity with respect to both the presence of postextubation stridor and the need for reintubation. With respect to the presence of complications associated with steroid use, few studies noted significant complications and these could not therefore be pooled.

II. What are the results?

1. What are the overall results of the review?

A. Prophylactic Intervention:

Combining neonatal and pediatric patients together showed a trend toward reduced reintubation rates without achieving statistical significance (total: n = 376, RR = 0.34, 95% CI = 0.05-2.33). In the evaluation of stridor prevention, both groups demonstrated significant reduction with corticosteroids (RR = 0.50, 95% CI = 0.28-0.88).

Neonatal Studies: These studies alone demonstrated both a trend toward reduced rate of reintubation with prophylactic intervention (n=160, RR = 0.2, 95% CI = 0.04-1.11) and a trend toward reduction in stridor prevalence in 109 patients (RR = 0.42, 95% CI = 0.07-2.32). Heterogeneity existed in both outcomes between studies suggesting perhaps that the multiple-dose strategy in the higher-risk patients of the Couser et al. and Courtney et al. studies is more effective than the single-dose regimen in lower-risk patients of the trial by Ferrara et al.

Pediatric Studies: Reintubation rates were not significantly reduced in the two pediatric prophylaxis trials (n = 216, RR = 0.49, 95% CI = 0.01-19.65). However, there was a significant reduction in postextubation stridor with intervention (RR = 0.53, 95% CI = 0.28-0.97). There was also a trend toward a reduction in racemic epinephrine use for postextubation stridor observed in these studies (RR = 0.38, 95% CI = 0.1-1.43). Heterogeneity also existed among all of these outcomes in these trials. In the Anene et al. study, significant reduction in reintubation rates, stridor and racemic epinephrine use was demonstrated, but the control rate of stridor and reintubation was also notably higher perhaps suggesting a higher-risk patient control group.

B. Treatment of Existing Postextubation Stridor

Harel et al. was the sole study assessing the effect of dexamethasone on postextubation stridor and reintubation in patients already reintubated for postextubation airway obstruction. In the 33 patients studied, dexamethasone had no effect on postextubation stridor score (weighted mean difference, -1.1; 95% CI = -3.7 to 1.5). The RR reduction on reintubation rate was 45%, but this did not reach statistical significance (RR = 0.55, 95% CI = 0.17-1.78).

C. Complications of Treatment

Few studies noted complications of steroid treatment. In Couser et al., 7 of 27 treated infants developed glucosuria, compared with 0 of 23 controls. Anene et al. noted one treated patient with GI bleeding, and 2 patients (one treated and one control) with hypertension.

2. How precise were the results?

As noted above.

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

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

Yes. A common thread among both the neonatal and pediatric randomized trials is that multiple dose dexamethasone therapy (i.e.. 0.5 mg/kg q6-8 hours for 3-6 total doses) confers some benefit primarily on high-risk patients (i.e., those with multiple or traumatic intubations). The heterogeneity among the populations examined does make it difficult to compare and contrast these studies. Some studies excluded those who had history of multiple intubations while other studies included patients with underlying airway abnormalities (e.g., subglottic stenosis and vocal cord paralysis). Some control populations had higher rates of stridor and reintubation than other control populations, and differences also existed in the amount of steroid used. Although this heterogeneity does cloud the picture, this meta-analysis does provide a better estimate for clinical use than the results of just one study.

2. Were all clinically important outcomes considered?

Yes. It would have been nice if all the studies used similar patient populations, similar stridor scores, similar steroid therapy and good documentation of adverse effects. This was not the case and therefore the focused nature of this meta-analysis does provide some clinically useful results without introducing more uncertainty by trying to assess outcomes that were not universally addressed by these randomized studies. Certainly there do exist other clinical variables that are extremely important when assessing for potential reactive edema in the glottic or subglottic mucosa because of pressure or irritation from an endotracheal tube (i.e., presence and degree of ETT air leak, overall fluid balance, duration of mechanical ventilation, etc.).

3. Are the benefits worth the harms and costs?

Yes. High-risk patients deserve consideration of this therapy and adopting this therapy for all patients in the ICU is still in question. There is room for further investigation comparing steroid use and ETT air leak, etc. Few studies noted complications that may have occurred and this certainly must be kept in mind when making this treatment decision.

References

1. Courtney SE, Weber KR, Siervogel RM, et al: Effects of dexamethasone on pulmonary function following extubation. J Perinatol 1992; 12: 246-251. [abstract]
2. Harel Y, Vardi A, Quigley R, et al: 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 1997; 39: 147-158. [abstract]
3. Ferrara TB, Georgieff MK, Ebert J, et al: Routine use of dexamethasone for the prevention of postextubation respiratory distress. J Perinatol 1989; 9: 287-290. [abstract]
4. Couser RJ, Ferrera B, Falde B, et al: Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. J Pediatr 1992; 121: 591-596. [abstract]
5. Anene O, Meert KL, Uy H, et al: Dexamethasone for the prevention of postextubation airway obstruction: A prospective, randomized, double-blind, placebo-controlled trial. Crit Care Med 1996; 24: 1666-1669. [abstract]
6. Tellez DW, Galvis AG, Storgion SA, et al: Dexamethasone in the prevention of postextubation stridor in children. J Pediatr 1991; 118: 289-94. [abstract]

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