12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial

Summary

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.

Introduction

Tracheal intubation for respiratory support is part of the routine acute care provided to critically ill patients, but can lead to substantial morbidity.1, 2 Despite use of high-volume and low-pressure cuff, postextubation laryngeal oedema is one of the most frequent and severe complications of tracheal intubation, since its incidence can reach 22%³ and can result in death.⁴ Laryngeal oedema typically occurs shortly after extubation,5, 6, 7 but is more common after a tracheal intubation for longer than 36 h.⁵ Importantly, severe laryngeal oedema is one of the main causes of respiratory distress after extubation⁸ that might require tracheal reintubation.3, 5, 6, 9, 10 The occurrence of postextubation laryngeal oedema can therefore result in prolonged mechanical ventilation with potential morbidity, additional cost, and longer intensive-care unit stay.

Experimental, autopsy, and clinical studies have shown that prolonged tracheal intubation can lead to oedema, inflammation, and ulceration of both the laryngeal and tracheal mucosa, especially at the level of the vocal cords and at the site of the cuff.1, 11, 12, 13, 14, 15 Animal studies have suggested that corticosteroids could reduce laryngeal infiltration by inflammatory cells secondary to prolonged intubation.¹⁵ However, only a few randomised studies have been done to investigate the ability of corticosteroids to prevent postextubation laryngeal oedema,3, 5, 7, 16, 17, 18, 19 and particularly few have been done in patients in intensive-care units.3, 5, 19 These studies have used different regimens, resulting in discrepant findings. We tested the hypothesis that pretreatment with corticosteroids initiated 12 h before a planned extubation might efficiently prevent the occurrence of postextubation laryngeal oedema in critically ill adults who had been mechanically ventilated for more than 36 h in an intensive-care unit.