Designing a Bayesian adaptive clinical trial to evaluate novel mechanical ventilation strategies in acute respiratory failure using integrated nested Laplace approximations.

BACKGROUND: Adaptive trials usually require simulations to determine values for design parameters, demonstrate error rates, and establish the sample size. We designed a Bayesian adaptive trial comparing ventilation strategies for patients with acute hypoxemic respiratory failure using simulations. The complexity of the analysis would usually require computationally expensive Markov Chain Monte Carlo methods but this barrier to simulation was overcome using the Integrated Nested Laplace Approximations (INLA) algorithm to provide fast, approximate Bayesian inference. METHODS: We simulated two-arm Bayesian adaptive trials with equal randomization that stratified participants into two disease severity states. The analysis used a proportional odds model, fit using INLA. Trials were stopped based on pre-specified posterior probability thresholds for superiority or futility, separately for each state. We calculated the type I error and power across 64 scenarios that varied the probability thresholds and the initial minimum sample size before commencing adaptive analyses. Two designs that maintained a type I error below 5%, a power above 80%, and a feasible mean sample size were evaluated further to determine the optimal design. RESULTS: Power generally increased as the initial sample size and the futility threshold increased. The chosen design had an initial recruitment of 500 and a superiority threshold of 0.9925, and futility threshold of 0.95. It maintained high power and was likely to reach a conclusion before exceeding a feasible sample size. CONCLUSIONS: We designed a Bayesian adaptive trial to evaluate novel strategies for ventilation using the INLA algorithm to efficiently evaluate a wide range of designs through simulation.

Effects of sevoflurane and its metabolite hexafluoroisopropanol on hypoxia/reoxygenation-induced injury and mitochondrial bioenergetics in murine cardiomyocytes.

Background: The volatile anaesthetic sevoflurane protects cardiac tissue from reoxygenation/reperfusion. Mitochondria play an essential role in conditioning. We aimed to investigate how sevoflurane and its primary metabolite hexafluoroisopropanol (HFIP) affect necrosis, apoptosis, and reactive oxygen species formation in cardiomyocytes upon hypoxia/reoxygenation injury. Moreover, we aimed to describe the similarities in the mode of action in a mitochondrial bioenergetics analysis. Methods: Murine cardiomyocytes were exposed to hypoxia (0.2% O2 for 6 h), followed by reoxygenation (air with 5% CO2 for 2 h) in the presence or absence sevoflurane 2.2% or HFIP 4 mM. Lactate dehydrogenase (LDH) release (necrosis), caspase activation (apoptosis), reactive oxygen species, mitochondrial membrane potential, and mitochondrial function (Seahorse XF analyser) were measured. Results: Hypoxia/reoxygenation increased cell death by 44% (+31 to +55%, P<0.001). Reoxygenation in the presence of sevoflurane 2.2% or HFIP 4 mM increased LDH release only by +18% (+6 to +30%) and 20% (+7 to +32%), respectively. Apoptosis and reactive oxygen species formation were attenuated by sevoflurane and HFIP. Mitochondrial bioenergetics analysis of the two substances was profoundly different. Sevoflurane did not influence oxygen consumption rate (OCR) or extracellular acidification rate (ECAR), whereas HFIP reduced OCR and increased ECAR, an effect similar to oligomycin, an adenosine triphosphate (ATP) synthase inhibitor. When blocking the metabolism of sevoflurane into HFIP, protective effects of sevoflurane - but not of HFIP - on LDH release and caspase were mitigated. Conclusion: Together, our data suggest that sevoflurane metabolism into HFIP plays an essential role in cardiomyocyte postconditioning after hypoxia/reoxygenation injury.

Outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation: a prospective observational study.

PURPOSE: Descriptive information on referral patterns and short-term outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation (ECMO) is lacking. METHODS: We conducted a prospective single-centre observational cohort study of ECMO referrals to Toronto General Hospital (receiving hospital) for severe respiratory failure (COVID-19 and non-COVID-19), between 1 December 2019 and 30 November 2020. Data related to the referral, the referral decision, and reasons for refusal were collected. Reasons for refusal were grouped into three mutually exclusive categories selected a priori: "too sick now," "too sick before," and "not sick enough." In declined referrals, referring physicians were surveyed to collect patient outcome on day 7 after the referral. The primary study endpoints were referral outcome (accepted/declined) and patient outcome (alive/deceased). RESULTS: A total of 193 referrals were included; 73% were declined for transfer. Referral outcome was influenced by age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95 to 0.96; P < 0.01) and involvement of other members of the ECMO team in the discussion (OR, 4.42; 95% CI, 1.28 to 15.2; P < 0.01). Patient outcomes were missing in 46 (24%) referrals (inability to locate the referring physician or the referring physician being unable to recall the outcome). Using available data (95 declined and 52 accepted referrals; n = 147), survival to day 7 was 49% for declined referrals (35% for patients deemed "too sick now," 53% for "too sick before," 100% for "not sick enough," and 50% for reason for refusal not reported) and 98% for transferred patients. Sensitivity analysis setting missing outcomes to directional extreme values retained robustness of survival probabilities. CONCLUSION: Nearly half of the patients declined for ECMO consideration were alive on day 7. More information on patient trajectory and long-term outcomes in declined referrals is needed to refine selection criteria.

RéSUMé: OBJECTIF: On manque d'informations descriptives sur les schémas de références et les devenirs à court terme des patient·es atteint·es d'insuffisance respiratoire n'ayant pas pu recevoir une oxygénation par membrane extracorporelle (ECMO). MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective monocentrique sur les références vers l'ECMO à l'Hôpital général de Toronto (hôpital d'accueil) pour insuffisance respiratoire grave (COVID-19 et non-COVID-19), entre le 1er décembre 2019 et le 30 novembre 2020. Les données relatives à la référence, à la décision de référence et aux motifs du refus ont été recueillies. Les motifs de refus ont été regroupés en trois catégories mutuellement exclusives sélectionnées a priori : « Trop malade maintenant ¼, « Trop malade avant ¼ et « Pas assez malade ¼. En ce qui concerne les références refusées, un sondage envoyé aux médecins traitant·es avait pour objectif de recueillir les devenirs des patient·es le jour 7 suivant la référence. Les critères d'évaluation principaux de l'étude étaient le résultat de la référence (accepté/refusé) et le devenir des patient·es (vivant·e/décédé·e). RéSULTATS: Au total, 193 références ont été incluses; le transfert a été refusé dans 73 % des cas. L'acceptation ou le refus de la référence était influencé par l'âge (rapport de cotes [RC], 0,97; intervalle de confiance [IC] à 95 %, 0,95 à 0,96; P < 0,01) et la participation d'autres membres de l'équipe ECMO à la discussion (RC, 4,42; IC 95 %, 1,28 à 15,2; P < 0,01). Les devenirs des patient·es étaient manquants pour 46 (24 %) des personnes référées (incapacité de localiser les médecins traitant·es ou incapacité des médecins de se souvenir du devenir). À l'aide des données disponibles (95 références refusées et 52 références acceptées; n = 147), la survie jusqu'au jour 7 était de 49 % pour les références refusées (35 % pour la patientèle jugée « trop malade maintenant ¼, 53 % pour celle « trop malade avant ¼, 100 % pour celle « pas assez malade ¼ et 50 % pour les cas où la raison du refus n'était pas déclarée) et 98 % pour les patient·es transféré·es. L'analyse de sensibilité établissant les résultats manquants à des valeurs extrêmes directionnelles a conservé la robustesse des probabilités de survie. CONCLUSION: Près de la moitié des patient·es pour lesquel·les un traitement sous ECMO a été refusé étaient en vie au jour 7. Davantage d'informations concernant la trajectoire et les devenirs à long terme des patient·es refusé·es sont nécessaires pour parfaire les critères de sélection.

Mechanical Ventilation after Traumatic Spinal Cord Injury-A Multicentric Cohort Study-based Prediction Model for Weaning Success: The BICYCLE Score.

Rationale: Limited information exists about the epidemiology, outcomes, and predictors of weaning from mechanical ventilation in patients with spinal cord injury. Objectives: Our aim was to investigate predictors of weaning outcomes for patients with traumatic spinal cord injury (tSCI) and develop and validate a prognostic model and score for weaning success. Methods: This was a registry-based, multicentric cohort study including all adult patients with tSCI requiring mechanical ventilation (MV) and admitted to one of the intensive care units (ICUs) of the Trauma Registry at St. Michael's Hospital (Toronto, ON, Canada) and the Canadian Rick Hansen Spinal Cord Injury Registry between 2005 and 2019. The primary outcome was weaning success from MV at ICU discharge. Secondary outcomes included weaning success at Days 14 and 28, time to liberation from MV accounting for competing risk of death, and ventilator-free days at 28 and 60 days. Associations between baseline characteristics and weaning success or time to liberation from MV were measured using multivariable logistic and competing risk regressions. A parsimonious model to predict weaning success and ICU discharge was developed and validated via bootstrap. A prediction score for weaning success at ICU discharge was derived, and its discriminative ability was assessed using receiver operating characteristic curve analysis and compared with the Injury Severity Score (ISS). Results: Of 459 patients analyzed, 246 (53.6%), 302 (65.8%), and 331 (72.1%) were alive and free of MV at Day 14, Day 28, and ICU discharge, respectively; 54 (11.8%) died in the ICU. Median time to liberation from MV was 12 days. Factors associated with weaning success were Blunt injury (odds ratio [OR], 2.96; P = 0.010), ISS (OR, 0.98; P = 0.025), Complete syndrome (OR, 0.53; P = 0.009), age in Years (OR, 0.98; P = 0.003), and Cervical LEsion (OR, 0.60; P = 0.045). The BICYCLE score showed a greater area under the curve than the ISS (0.689 [95% confidence interval (CI), 0.631-0.743] vs. 0.537 [95% CI, 0.479-0.595]; P < 0.0001). Factors predicting weaning success also predicted time to liberation. Conclusions: In a large multicentric cohort, 72% of patients with tSCI were weaned and discharged alive from the ICU. Readily available admission characteristics can reasonably predict weaning success and help prognostication.

Limiting Dynamic Driving Pressure in Patients Requiring Mechanical Ventilation.

OBJECTIVES: Previous studies reported an association between higher driving pressure (∆P) and increased mortality for different groups of mechanically ventilated patients. However, it remained unclear if sustained intervention on ∆P, in addition to traditional lung-protective ventilation, improves outcomes. We investigated if ventilation strategies limiting daily static or dynamic ∆P reduce mortality compared with usual care in adult patients requiring greater than or equal to 24 hours of mechanical ventilation. DESIGN: For this comparative effectiveness study, we emulated pragmatic clinical trials using data from the Toronto Intensive Care Observational Registry recorded between April 2014 and August 2021. The per-protocol effect of the interventions was estimated using the parametric g-formula, a method that controls for baseline and time-varying confounding, as well as for competing events in the analysis of longitudinal exposures. SETTING: Nine ICUs from seven University of Toronto-affiliated hospitals. PATIENTS: Adult patients (≥18 yr) requiring greater than or equal to 24 hours of mechanical ventilation. INTERVENTIONS: Receipt of a ventilation strategy that limited either daily static or dynamic ∆P less than or equal to 15 cm H 2 O compared with usual care. MEASUREMENTS AND MAIN RESULTS: Among the 12,865 eligible patients, 4,468 of (35%) were ventilated with dynamic ∆P greater than 15 cm H 2 O at baseline. Mortality under usual care was 20.1% (95% CI, 19.4-20.9%). Limiting daily dynamic ∆P less than or equal to 15 cm H 2 O in addition to traditional lung-protective ventilation reduced adherence-adjusted mortality to 18.1% (95% CI, 17.5-18.9%) (risk ratio, 0.90; 95% CI, 0.89-0.92). In further analyses, this effect was most pronounced for early and sustained interventions. Static ∆P at baseline were recorded in only 2,473 patients but similar effects were observed. Conversely, strict interventions on tidal volumes or peak inspiratory pressures, irrespective of ∆P, did not reduce mortality compared with usual care. CONCLUSIONS: Limiting either static or dynamic ∆P can further reduce the mortality of patients requiring mechanical ventilation.

Linking Acute Physiology to Outcomes in the ICU: Challenges and Solutions for Research.

ICU clinicians rely on bedside physiological measurements to inform many routine clinical decisions. Because deranged physiology is usually associated with poor clinical outcomes, it is tempting to hypothesize that manipulating and intervening on physiological parameters might improve outcomes for patients. However, testing these hypotheses through mathematical models of the relationship between physiology and outcomes presents a number of important methodological challenges. These models reflect the theories of the researcher and can therefore be heavily influenced by one's assumptions and background beliefs. Model building must therefore be approached with great care and forethought, because failure to consider relevant sources of measurement error, confounding, coupling, and time dependency or failure to assess the direction of causality for associations of interest before modeling may give rise to spurious results. This paper outlines the main challenges in analyzing and interpreting these models and offers potential solutions to address these challenges.

Hexafluoroisopropanol decreases liver ischemia-reperfusion injury by downregulation of high mobility group box-1 protein.

Liver ischemia-reperfusion (IR) injury is associated with poor outcome after liver transplantation and liver resections. Hexafluoroisopropanol (HFIP) is a tri-fluorinated metabolites of volatile anesthetics and has modulatory effects on inflammation that have been observed mainly in cell culture experiments. In this survey, we investigated the effects of HFIP in a rat model of normothermic hepatic ischemia-reperfusion injury. Twenty-four male Wistar rats were randomized into three groups: (1) control in which animals were submitted to 30 min of partial liver ischemia with resection of non-ischemic liver lobes immediate after reperfusion, (2) pre-ischemia (PI) group in which animals received intravenous HFIP (67 mg/kg) 5 min before liver ischemia, and (3) pre-reperfusion (PR) group in which animals received intravenous HFIP (67 mg/kg) 5 min before reperfusion. Four hours after reperfusion, all animals were euthanized for sample collection. Aspartate and alanine transaminases, glucose, and high mobility group box-1 (HMGB-1) protein concentrations showed a significant decreased, and malondialdehyde was increased in the PR group compared with control and PI groups. Interleukin 6 (IL-6) was increased in the PI group compared with control and PR groups. IL-10 and -12 were increased in the PR and PI groups, respectively, when compared with the control group. Glucose decreased in the PR when compared with the control group. Post-conditioning with HFIP led to a decrease in hepatocellular injury and was associated with a downregulation of HMGB-1. The HFIP resulted in a better control of inflammatory response to ischemia-reperfusion even without causing a reduction in oxidative stress.

Transesophageal Echocardiography-Guided Extracorporeal Membrane Oxygenation Cannulation in COVID-19 Patients.

OBJECTIVES: A paucity of data supports the use of transesophageal echocardiography (TEE) for bedside extracorporeal membrane oxygenation (ECMO) cannulation. Concerns have been raised about performing TEEs in patients with COVID-19. The authors describe the use and safety of TEE guidance for ECMO cannulation for COVID-19. DESIGN: Single-center retrospective cohort study. SETTING: The study took place in the intensive care unit of an academic tertiary center. PARTICIPANTS: The authors included 107 patients with confirmed SARS-CoV-2 infection who underwent bedside venovenous ECMO (VV ECMO) cannulation under TEE guidance between May 2020 and June 2021. INTERVENTIONS: TEE-guided bedside VV ECMO cannulation. MEASUREMENTS: Patient characteristics, physiologic and ventilatory parameters, and echocardiographic findings were analyzed. The primary outcome was the number of successful TEE-guided bedside cannulations without complications. The secondary outcomes were cannulation complications, frequency of cannula repositioning, and TEE-related complications. MAIN RESULTS: TEE-guided cannulation was successful in 99% of the patients. Initial cannula position was adequate in all but 1 patient. Fourteen patients (13%) required cannula repositioning during ECMO support. Forty-five patients (42%) had right ventricular systolic dysfunction, and 9 (8%) had left ventricular systolic dysfunction. Twelve patients (11%) had intracardiac thrombi. One superficial arterial injury and 1 pneumothorax occurred. No pericardial tamponade, hemothorax or intraabdominal bleeding occurred in the authors' cohort. No TEE-related complications or COVID-19 infection of healthcare providers were reported during this study. CONCLUSIONS: Bedside TEE guidance for VV ECMO cannulation is safe in patients with severe respiratory failure due to COVID-19. No tamponade or hemothorax, nor TEE-related complications were observed in the authors' cohort.

Evaluation of an advanced critical care echocardiography program: a mixed methods study.

PURPOSE: Limited data exist on advanced critical care echocardiography (CCE) training programs for intensivists. We sought to describe a longitudinal echocardiography program and investigate the effect of distributed conditional supervision vs predefined en-bloc supervision, as well as the effect of an optional echocardiography laboratory rotation, on learners' engagement. METHODS: In this mixed methods study, we enrolled critical care fellows and faculty from five University of Toronto-affiliated intensive care units (ICU) between July 2015 and July 2018 in an advanced training program, comprising theoretical lectures and practical sessions. After the first year, the program was modified with changes to supervision model and inclusion of a rotation in the echo laboratory. We conducted semistructured interviews and investigated the effects of curricular changes on progress toward portfolio completion (150 transthoracic echocardiograms) using a Bayesian framework. RESULTS: Sixty-five learners were enrolled and 18 were interviewed. Four (9%) learners completed the portfolio. Learners reported lack of time and supervision, and skill complexity as the main barriers to practicing independently. Conditional supervision was associated with a higher rate of submitting unsupervised echocardiograms than unconditional supervision (rate ratio, 1.11, 95% credible interval, 1.08 to 1.14). After rotation in the echocardiography laboratory, submission of unsupervised echocardiograms decreased. CONCLUSION: Trainees perceived lack of time and limited access to supervision as major barriers to course completion. Nevertheless, successful portfolio completion was related to factors other than protected time in the echocardiography laboratory or unconditional direct supervision in ICU. Further research is needed to better understand the factors promoting success of CCE training programs.

RéSUMé: OBJECTIF: Il n'existe que peu de données sur les programmes de formation avancés en échocardiographie pour les soins intensifs (écho-USI) destinés aux intensivistes. Nous avons cherché à décrire un programme longitudinal d'échocardiographie et à étudier l'effet d'une supervision conditionnelle distribuée vs une supervision prédéfinie en bloc, ainsi que l'effet d'une rotation facultative en laboratoire d'échocardiographie, sur le niveau d'implication des apprenants. MéTHODE: Dans cette étude à méthodes mixtes, nous avons recruté des fellows en soins intensifs et des professeurs de cinq unités de soins intensifs (USI) affiliées à l'Université de Toronto entre juillet 2015 et juillet 2018 pour participer à un programme de formation avancée comprenant des conférences théoriques et des séances pratiques. Après la première année, le programme a été modifié en apportant des changements au modèle de supervision et en incluant une rotation dans le laboratoire d'écho. Nous avons mené des entretiens semi-structurés et étudié les effets des changements du programme d'études sur les progrès vers la réussite de la formation (150 échocardiogrammes transthoraciques) en utilisant un cadre bayésien. RéSULTATS: Soixante-cinq apprenants étaient inscrits et 18 ont été interviewés. Quatre (9 %) apprenants ont complété la formation. Les apprenants ont signalé que le manque de temps et de supervision ainsi que la complexité des compétences constituaient les principaux obstacles à une pratique autonome. La supervision conditionnelle était associée à un taux plus élevé de soumission d'échocardiogrammes non supervisés que la supervision inconditionnelle (ratio de taux, 1,11, intervalle crédible à 95 %, 1,08 à 1,14). Après la rotation dans le laboratoire d'échocardiographie, la soumission d'échocardiogrammes non supervisés a diminué. CONCLUSION: Les stagiaires ont perçu le manque de temps et l'accès limité à la supervision comme des obstacles majeurs à la réussite de la formation. Néanmoins, l'achèvement du cours était lié à des facteurs autres que le temps protégé au laboratoire d'échocardiographie ou la supervision directe inconditionnelle aux soins intensifs. D'autres recherches sont nécessaires pour mieux comprendre les facteurs favorisant le succès des programmes de formation en écho-USI.

Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study.

OBJECTIVE: To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. DESIGN: Observational study. SETTING: 30 countries across five continents, 3 January 2020 to 29 August 2021. PARTICIPANTS: 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. INTERVENTIONS: ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. MAIN OUTCOME MEASURE: The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. RESULTS: 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO2/FiO2 ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference -7.1%, 95% confidence interval -8.2% to -6.1%; risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO2/FiO2 <80 mm Hg or with driving pressures >15 cmH2O during the first 10 days of mechanical ventilation. CONCLUSIONS: ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

Testing for non-inferior mortality: a systematic review of non-inferiority margin sizes and trial characteristics.

OBJECTIVE: To describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size. DESIGN: Systematic review. DATA SOURCES: Medline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019. ELIGIBILITY CRITERIA: Prospective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention. RESULTS: 3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%-10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3-1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size. CONCLUSION: Absolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials.

Mental Practice as an Additional Step Before Simulation Practice Facilitates Training in Bronchoscopic Intubation.

BACKGROUND: Learning bronchoscopy is challenging for novices, as it requires navigation in a 3-dimensional space under 2-dimensional viewing conditions and execution of complex motor skills with an unfamiliar instrument. Mental practice exercises are based on repeated visualization of motor actions without physically performing them, thereby promoting the learning of skills. We aimed to evaluate whether a teaching intervention including mental practice exercise modules for the acquisition of bronchoscopy skills improves fiberoptic intubation performance of novice learners. METHODS: In this prospective cohort study, 24 pediatric intensive care trainees and respiratory therapists participating in a bronchoscopy learning curriculum in 2016-2017 attended a theoretical lecture followed by self-guided learning. Subsequently, the learners were randomly assigned to either participating in a teaching intervention including mental practice exercises or not (control group). The primary outcome was time to complete their first bronchoscopic intubation using a virtual reality simulator. Secondary outcomes were the occurrence of "red outs" (ie, the anatomy could no longer be visualized) or collisions with the airway wall. Bayesian Poisson Mixture models were used to estimate the effect of the intervention on outcomes. Furthermore, participation in the teaching intervention was examined in short interviews and with descriptive thematic analysis. RESULTS: Subjects in the intervention group completed the bronchoscopy on average 1.2 times faster (rate ratio 1.2 [95% credible intervals 1.1-1.3]). The posterior probability that the teaching intervention reduced the occurrence of "red outs" by more than half was 86%. No differences were found regarding the odds of colliding with the airway wall. Everyone except 1 trainee in the mental practice group engaged with and found the mental practice modules helpful. CONCLUSIONS: A teaching intervention including mental practice exercises represents a valuable additional learning strategy promoting the performance and complex skill acquisition of novice learners in the initial stages of learning bronchoscopy procedures.