Abstract
BACKGROUND: Endotracheal tubes with subglottic ports and a polyurethane cuff are recommended for reducing microaspiration in patients who are ventilated. However, their long-term safety and efficacy after emergency intubation are uncertain. METHODS: In this randomised controlled phase 2 trial conducted at two single centres (Oregon Health and Science University [OHSU, Portland, OR, USA] and Yale New Haven Hospital [YNHH, New Haven, CT, USA]), all patients aged 18 years or older requiring endotracheal intubation either in the emergency department or elsewhere in hospital for acute respiratory distress or failure were randomly assigned to receive a polyurethane-cuffed endotracheal tube with subglottic suction (PU-EVAC) or a polyvinylchloride-cuffed endotracheal tube (PVC). Individuals who were electively intubated in the operating room and protected populations (children [aged younger than 18 years], pregnant women, and prisoners) were ineligible to participate. Patients were randomised 1:1 into the two treatment arms using a fair coin randomisation scheme. Patients assigned to the PVC group were treated according to usual care, and patients assigned to the PU-EVAC group received continuous subglottic suctioning until removal of the endotracheal tube. The coprimary endpoints at 6 months were laryngeal injury, quality of life (Short Form-36 [SF-36] physical component summary [PCS] and mental component summary [MCS] scores), and cognitive function. Secondary endpoints were infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (VAP). This trial is registered at ClinicalTrials.gov (NCT03705286) and is now completed. FINDINGS: Between May 6, 2019, and July 31, 2019 (Oregon Health and Science University), and Sept 29, 2020, to Feb 11, 2022 (Yale New Haven Hospital), 1074 adult patients were enrolled and 1068 were randomly assigned to either the PVC (n=533) or the PU-EVAC (n=535) endotracheal tube group. Participants had a mean age at intubation of 62·9 years (SD 15·7), were mostly male (671 [63%] of 1068), and mostly White (718 [67%]). IVAC occurred in 43 (8%) of 535 patients in the PU-EVAC group and in 33 (6%) of 533 patients in the PVC group (risk difference 0·02 [95% CI -0·01 to 0·05]); possible VAP occurred in 30 (6%) patients in the PU-EVAC group and 24 (5%) patients in the PVC group (0·01 [-0·02 to 0·04]). At 6-month follow-up, 558 patients had died (274 [51%] in the PU-EVAC group and 284 [53%] in the PVC group). 157 completed the 6-month follow-up visit. Laryngeal injury was reported in 71 (83%) of 86 patients in the PU-EVAC group and in 49 (70%) of 70 patients in the PVC group (0·11 [-0·03 to 0·20]; p=0·098). Mean PCS was 39·97 (SD 10·97) in the PU-EVAC group and 40·49 (11·92) in the PVC group (mean difference -0·52 [95% CI -4·21 to 3·17]; p=0·78) and mean MCS was 45·91 (13·10) in the PU-EVAC group and 48·89 (12·22) in the PVC group (-2·98 [-7·03 to 1·07]; p=0·15). Cognitive impairment was present in 70 (85%) of 82 in the PU-EVAC group and 54 (81%) of 67 patients in the PVC group (risk difference 0·05 [-0·07 to 0·17]; p=0·44). INTERPRETATION: The PU-EVAC did not reduce the incidence of IVAC or possible VAP compared with a standard PVC endotracheal tube with no subglottic drainage. At 6-month follow-up, neither quality of life, cognitive function, nor laryngeal injury differed between groups. However, the small number of survivors who provided information on their physical and mental status limits the conclusions that can be drawn regarding long-term outcome differences. FUNDING: National Institutes of Health and National Heart, Lung, and Blood Institute.