INTRODUCTION Endotracheal intubation and mechanical ventilation are lifesaving interventions. However, as with acute interventions, can be associated with serious complications. One such complication is laryngeal edema (LE) that occurs in 4-55% of patients. LE is thought to be caused by marked polymorphonuclear infiltration to the traumatized upper airway postintubation. The incidence of LE increases as the duration of intubation accrues, but it can occur as early as the first 24 hours of intubation. LE can result in airway narrowing and increased airflow velocity. It is postulated that narrowing of the lumen by 50% or more may result in postextubation stridor and respiratory distress. As a result, 3.5% (range 0-10.5%) of patients with LE will fail an extubation attempt and require reintubation. For various reasons, reintubation has a significant morbidity and mortality.

Identifying patients with LE can be challenging, the presence of the endotracheal tube (ETT) precludes direct visualization of the upper airway prior to extubation, therefore, clinicians cannot accurately predict airway obstruction before it occurs. A cuff-leak test (CLT) was first described in 1988 as a surrogate for direct visualization and a screening for airway edema prior to extubation. This test involves deflating the balloon cuff on an ETT and observing if the patient is able to breathe around it. If air can pass around the ETT, it suggest that the airway is patent and clinicians may proceed with extubation. A small leak or complete absence of one, would suggest an airway obstruction.

There are conflicting results on the utility and accuracy of a CLT. To date, two meta-analyses of observational studies examined the diagnostic accuracy of a CLT. One meta-analysis reports that a failed CLT is insensitive but a specific predictor of LE (pooled sensitivity and specificity 0.56; 95% CI, 0.48-0.63 and 0.92; 95% CI, 0.90-0.93, respectively) and reintubation (pooled sensitivity and specificity for reintubation 0.63; 95% CI, 0.38-0.84 and 0.86; 95% CI, 0.81-0.90, respectively). While the second meta-analysis also states that the failed CLT was associated with postextubation LE, particularly in patients with \> 5 days duration of intubation (odds ratio \[OR\]=2.09; 95% CI, 1.28-2.89), it was not associated with higher odds of reintubation (OR=0.94; 95% CI, 0.32-1.57).

Despite the lack of high quality studies, an absent cuff leak usually results in delayed extubation and exposure to corticosteroids to empirically treat airway edema. A recent meta-analysis of 11 parallel randomized controlled trails (RCTs) with a total of 2472 patients examined the effect of prophylactic corticosteroids prior to extubation on postextubation stridor and reintubation. Prophylactic corticosteroids use reduced the risk of postextubation airway events when compared to placebo or no treatment (RR 0.43; 95% CI 0.29-0.66, P=0.002). A subgroup analysis demonstrates that this benefit is only significant in patients that are deemed "high risk" for LE. Prophylactically treating unspecified patients shows no reduction in postextubation events and exposes patients to high dose steroids (16). Moreover, a false positive CLT can unnecessarily delay extubation, leading to a prolonged length of stay in the intensive care unit (ICU), barotraumas, and increased risk of ventilator associated pneumonias, therefore, exposing patients unnecessarily to these undesirable outcomes. On the other hand, if a CLT is not performed, or if in case of a false negative test, some patients may fail the extubation attempt and require reintubation.

Recent clinical practice guidelines for using CLT reflect this uncertainty. The American Thoracic Society guidelines on liberation of mechanical ventilation issued a weak recommendation for performing CLT in mechanically ventilated adults who are at high risk for postextubation stridor (conditional recommendation, very low certainty). There is also significant clinical equipoise. A recent unpublished survey found that 42% (12/26) of Canadian intensive care unit (ICU) physicians either never or rarely request to know the results of a cuff leak test prior to extubating a patient that is at moderate risk of laryngeal edema while 23% will always or usually order the test. Therefore, a large RCT is necessary to investigate the diagnostic accuracy of the CLT and its impact on patients' outcomes.

Herein, the investigators are reporting the protocol for the COMIC Pilot Trial. The COMIC (Cuff leak and airway Obstruction in Mechanically ventilated ICU patients) pilot trial will be a multicenter, randomized, concealed, blinded, parallel-group, pragmatic pilot trial. The purpose is to determine the feasibility of undertaking a powered RCT to examine the impact of CLT on postextubation stridor and reintubation. Subsequently, describing the diagnostic accuracy of this test.