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Three Part Question

In [mechanically ventilated children] does [corticosteroid administration] reduce [the chance of reintubation due to laryngeal oedema]?

Clinical Scenario

John, a 4 year old boy, has been mechanically ventilated for three days during recovery from a blunt chest trauma. According to his level of ventilator support, he is considered to be ready to be extubated. The previous patient had to be reintubated as a result of postextubation laryngeal oedema. You wonder whether corticosteroids may reduce this risk of extubation failure.

Search Strategy

Pubmed: (Anti-Inflammatory Agents OR Anti-Inflammatory Agents/therapeutic use OR Anti-Inflammatory Agents/therapy OR hydroxycorticosteroids) AND systematic[sb]) AND ("Intubation, Intratracheal"[MeSH] OR "Respiration, Artificial"[MeSH]); 25 references, 2 relevant studies
("reintubation" or ("failure" and "extubation")) AND (Anti-Inflammatory Agents OR Anti-Inflammatory Agents/therapeutic use OR Anti-Inflammatory Agents/therapy OR hydroxycorticosteroids); 30 references, with 4 relevant
"reintub*" AND "steroids"; 30 references, 7 relevant
Secondary sources
Cochrane Database of Systematic Reviews; 1 limited to newborn infants.
PubMed clinical queries
"Respiration, Artificial"[MESH] AND (Hydroxycorticosteroids)[MESH] AND systematic; 1 reference not related to the question.
("Intubation, Intratracheal"[MeSH]) AND systematic[sb] AND (Hydroxycorticosteroids)[MESH]; no references.

Search Outcome

7 relevant overall

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Davis and Henderson-Smart, 2001,	3 randomised controlled trials (RCTs) addressing the effects of treatment with dexamethasone to facilitate extubation of newborn infants. n = 160, reintubation treatment group 12/119, control group 16/120	Systematic review (level 1a)	Need for endotracheal intubation	Neonates overall: RRR 87% (95% CI 17 to 100%), ARR 0.09 (95% CI 0.02 to 0.16). NNT 11 (95% CI 6 to 60) Neonates, high-risk group: RRR 100% (95% CI –39 to 100%), ARR 0.17 (95% CI 0.02 to 0.33). NNT 6 (95% CI 3 to 52)	Study limited to neonates. Reintubation rate as a result of laryngeal oedema alone not clearly stated
Meade et al, 2001,	Three RCTs that addressed whether pre-extubation steroid administration reduces post-extubation complications in children, including one study on children with previous failed intubation3. n = 239, reintubation treatment group 12/119, control group 16/120	Systematic review (level 1a)	Need for endotracheal intubation	Children overall: RRR 24% (95% CI –37 to 85%), ARR 0.03 (95% CI –0.05 to 0.11) Children, high-risk group: RRR 45% (95% CI –39 to 100%), ARR 0.20 (95% CI –0.18 to 0.59)	Randomisation not clearly stated in two trials, two trials limited to primary extubation. Heterogeneity between studies on dose-regimen, inclusion criteria and outcome
Markovitz and Randolph, 2002,	Six RCTs, five of which on the use of steroids for the prevention of reintubation in children and/or neonates. One paediatric study on children with previous failed intubation was excluded3 Neonates: n = 160, reintubation treatment group 1/80, control group 4/80. Children: n = 216, reintubation treatment group 9/107, control group 11/107	Systematic review (level 1a)	Need for endotracheal intubation	Neonates: RRR 87% (95% CI 17 to 100%), ARR 0.09 (95% CI 0.02 to 0.16). NNT 11 (95% CI 6 to 60) Children (overall): RRR 17% (95% CI –60 to 93%), ARR 0.02 (95% CI –0.06 to 0.09)	Heterogeneity between studies on dose-regimen, inclusion criteria and outcome

Comment(s)

The outcome, requirement for endotracheal reintubation, is of clinical importance in the spectrum of those relating to paediatric intensive care. Paediatric intensive care patients with failed intubation have longer hospital, paediatric intensive care, and ventilator courses, leading to additional costs, risks, and patient burden. The risk of reintubation in this patient group is above 10% (Meade, Harel, Anene). In the ex-preterm intubated newborn, prophylactic corticosteroids reduce the need for reintubation. In the paediatric population, the benefit of prophylaxis is less clear. The overall benefit is estimated at 1 in 59 children succeeding extubation when they would have failed without corticosteroid prophylaxis. However, the study size means that the true value may be that as few as 11 children need to be treated, or indeed that treating 17 children causes one an additional failure that would not have occurred if a placebo had been given. Limiting prophylaxis to children at risk for developing post-extubation laryngeal oedema (e.g. multiple airway manipulations, or failed prior extubation), the benefit seems to improve. In this patient group, five children (95% CI 3 to 13) have to be treated to avoid one reintubation. Dexamethasone is a potent glucocorticoid with many effects beyond reducing airway oedema. The disturbance to glucose metabolism is well demonstrated (Couser). although the clinical relevance has yet to be shown. Prophylactic use of dexamethasone was not associated with the development of hypertension in neonates (Davis, Meade, Harel, Anene, Couser). Anene et al noted one patient treated with gastrointestinal bleeding.4 The drug is not without side effects and defining the group of children in whom it is most likely to be effective seems desirable, since the trend towards a favourable effect of prophylaxis is most expressed in this group. The studies had relatively few patients, and showed significant heterogeneity. As a result the power of the data is limited. Furthermore, the dose regimen varied between the studies, varying from a single low dose immediately prior to extubation to multiple high doses given 24 hours prior to extubation. A well designed, adequately powered prospective study limited to patients at risk for extubation failure, to assess the benefits and side effects of prophylactic steroid treatment in this group of paediatric patients is warranted to draw firm conclusions. Awaiting such a trial one could argue that, given the impact of endotracheal reintubation, the costs associated with failed extubation, the relative low costs of accepting a significant NNT, and the absence of clinical significant side effects, prophylactic multiple dose corticosteroid administration prior to extubation in high risk neonatal and paediatric patients can be defended. Given the lack of effect in low risk patients and potential side effects, it seems reasonable to withhold steroid prophylaxis in these patients.

Clinical Bottom Line

Extubation failure in children, due to post-extubation laryngeal oedema occurs in about 10% of patients. (Grade B) Steroid prophylaxis reduces reintubation rate in high risk neonates and children (e.g. children with multiple airway manipulations) receiving multiple dose dexamethasone. (Grade B) Steroid prophylaxis does not reduce extubation failure in low risk paediatric patients. (Grade B)

References

1. Davis PG, Henderson-Smart DJ. Intravenous dexamethasone for extubation of newborn infants. Cochrane Database Syst Rev 2001;(4):CD000308.
2. Meade MO, Guyatt GH, Cook DJ. et al. Trials of corticosteroids to prevent postextubation airway complications. Chest 2001;120(6 suppl):464S-8S.
3. 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;39:147–58.
4. 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;24:1613–14.
5. Couser RJ, Ferrara TB, Falde B. et al. Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. J Pediatr 1992;12:591–6.
6. Ferrara TB, Georgieff MK, Ebert J. et al. Routine use of dexamethasone for the prevention of postextubation respiratory distress. J Perinatol 1989;9:287–90.
7. Markovitz BP, Randolph AG. Corticosteroids for the prevention of reintubation and postextubation stridor in pediatric patients: a meta-analysis. Pediatr Crit Care Med 2002;3:223–6.