Therapy 12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial.
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Summary
Posted By:	Gordon Doig
E-Mail:	Gordon.Doig@EvidenceBased.net
Posted Date:	7 June 2007
Title:	12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial.
Authors:	François B, Bellissant E, Gissot V, Desachy A, Normand S, Boulain T, Brenet O, Preux PM, Vignon P; Association des Réanimateurs du Centre-Ouest (ARCO).
Reference:	Lancet. 2007 Mar 31;369(9567):1083-9.
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	BACKGROUND: The efficacy of corticosteroids in reducing the incidence of postextubation laryngeal oedema is controversial. We aimed to test our hypothesis that methylprednisolone started 12 h before a planned extubation could prevent postextubation laryngeal oedema. METHODS: We did a placebo-controlled, double-blind multicentre trial in 761 adults in intensive-care units. Patients who were ventilated for more than 36 h and underwent a planned extubation received intravenous 20 mg methylprednisolone (n=380) or placebo (381) 12 h before extubation and every 4 h until tube removal. The primary endpoint was occurrence of laryngeal oedema within 24 h of extubation. Laryngeal oedema was clinically diagnosed and deemed serious if tracheal reintubation was needed. Analyses were done on a per protocol and intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00199576. FINDINGS: 63 patients could not be assessed, mainly because of self-extubation (n=16) or cancelled extubation (44) between randomisation and planned extubation. 698 patients were analysed (343 in placebo group, 355 in methylprednisolone group). Methylprednisolone significantly reduced the incidence of postextubation laryngeal oedema (11 of 355, 3%vs 76 of 343, 22%, p<0.0001), the global incidence of reintubations (13 of 355, 4%vs 26 of 343, 8%, p=0.02), and the proportion of reintubations secondary to laryngeal oedema (one of 13, 8 %vs 14 of 26, 54%, p=0.005). One patient in each group died after extubation, and atelectasia occurred in one patient given methylprednisolone. INTERPRETATION: Methylprednisolone started 12 h before a planned extubation substantially reduced the incidence of postextubation laryngeal oedema and reintubation. Such pretreatment should be considered in adult patients before a planned extubation that follows a tracheal intubation of more than 36 h.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Yes. Patients were randomised using sequentially numbered, opaque sealed envelopes (SNOSE). For an excellent methods paper on how to use the SNOSE technique properly, click here.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	Yes. the Figure on page 1084 shows how many patients were screened, enrolled and randomised. It is important to note that this Figure does not clearly and explicitly show how many patients were included in the author's Intention to Treat analysis. Even when such a flow diagram DOES mention the number of patients included in the ITT analysis, it is always a good idea to double check by reviewing the N of the actual analysis. In this specific trial, the first paragraph of the second column on page 1086 reports that ALL randomised patients (381 palcebo vs 380 methylpred) were included in the ITT analysis of the primary outcome (stridor). Indeed, the authors report that if the primary outcome could not be assessed on patients, they made very conservative assumptions. They assumed that ALL control patients who were not evaluated for stridor did well and all Methylpred patients with missing stridor evaluations did poorly.
2b. Were patients analyzed in the groups to which they were randomized?
	Yes. There were no cross-overs. If a patient was unable to receive Methylpred, the ITT analysis still included them in the Methylpred group. This is the most conservative assumption.
3. Were patients, health workers, and study personnel blind to treatment?
	Yes. A placebo control was used. This would have blinded patients, health workers and outcome assessors.
4. Were the groups similar at the start of the trial?
	Yes. The authors report a very minor difference in nasal vs oral intubation rates (10% vs 6%). When subsequent analysis was adjusted for this minor difference, the relationship between intervention and outcome was not changed.
5. Aside from the experimental intervention, were the groups treated equally?
	Uncertain. A table of other treatments received AFTER ranomisation is not provided.
What are the Results?
1. How large was the treatment effect?
	Primary (ITT) analysis: Stridor/Laryngeal edema: 9% Methylpred vs 20% placebo (P<0.0001) Note - the authors do not provide an ITT analysis for intubation. I calculated the below rates using the same conservative assumptions the authors used for laryngeal edema: Missing MP pts DID need reintubation and missing controls did NOT. Reintubations: 39/380 (10%) MP vs 26/381 (7%) placebo (P=0.09)
2. How precise was the estimate of the treatment effect?
	Primary (ITT) analysis: Stridor/Laryngeal edema: 11.3% ARR with 95%CI 6% to 16% reduction 8.9 NNT with 95% CI 6 to 15.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	Yes. This paper addresses a problem that may be important to many intubated patients.
2. Were all clinically important outcomes considered?
	No. Although there is no reason to believe this intervention could alter mortality, it should be reported routinely in all ICU-based trials. It is unfortunate that a true ITT analysis was not reported for reintubations. In consideration of the negative findings under conservative ITT assumptions, the positive findings of the per protocol analysis should be interpreted with caution. It may be important to follow duration of ventilation and subsequent VAP in all reintubations.
3. Are the likely treatment benefits worth the potential harms and costs?
	Unknown.
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