Exclusion Criteria 1. Operator or supervisor feels specific intra- procedural laryngoscopy device will be required.

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1 FELLOW Study Data Analysis Plan Direct Laryngoscopy vs Video Laryngoscopy Background Respiratory failure requiring endotracheal intubation occurs in as many as 40% of critically ill patients. Procedural complications including failed attempts at intubation, esophageal intubation, arterial oxygen desaturation, aspiration, hypotension, cardiac arrest, and death are common in this setting. While there are many important components of successful airway management in critical illness, the maintenance of adequate arterial hemoglobin saturation from procedure initiation until endotracheal tube placement is paramount as desaturation is the most common factor associated with periintubation cardiac arrest and death. Interventions that either shorten the duration of time required for tube placement or prolong the period before desaturation may be effective in improving outcome. The high rate of complications and the lack of existing evidence regarding the efficacy of current airway management techniques in shortening the time to airway establishment or prolonging the time to desaturation mandates further investigation. Video laryngoscopy may increase the rate of first intubation attempt success and improve the safety of intubating critically ill patients. Patient Population Adult patients undergoing intubation in the medical intensive care unit of an academic, tertiary care hospital. Inclusion Criteria 1. Patients undergoing intubation in the Medical ICU 2. Planned operator is a pulmonary and critical care medicine fellow 3. Administration of sedation and/or neuromuscular blockade is planned Exclusion Criteria 1. Operator or supervisor feels specific intra- procedural laryngoscopy device will be required. Specific Hypothesis Video laryngoscopy will be superior to direct laryngoscopy in successful first attempt at endotracheal intubation (defined by confirmed placement of an endotracheal tube in the trachea during first laryngoscopy attempt) after controlling for the operator s past number of procedures with the equipment used. Variable Definitions Primary Outcome The primary outcome for the laryngoscopy study will be first attempt success rate (defined as the placement of an endotracheal tube in the trachea after the first insertion of the laryngoscope into the oral cavity without the use of any other devices) with video laryngoscopy compared with direct laryngoscopy. The primary analysis will be adjusted for the number of times

2 the operator has previously used the assigned laryngoscopy device at the time of the procedure. Secondary Outcomes Secondary efficacy outcomes will include: 1. Unadjusted analysis of successful first attempt of endotracheal intubation 2. Time from initiation of sedation and/or paralysis to the successful placement of an endotracheal tube in the trachea. 3. Number of attempts to successfully intubate the trachea 4. Need for second operator 5. Need for additional intubating equiptment 6. Grade of view on first attempt Secondary safety outcomes will include: 1. Incidence of hypoxemia as defined by lowest oxygen saturation less than 90% 2. Procedural Hypotension 3. Number of esophageal intubations 4. Airway trauma 5. Incidence of post- intubation tube malposition on CXR Tertiary Outcomes Tertiary outcomes will include: 1. In- hospital mortality 2. Ventilator- free days (VFDs) 3. ICU- free days Data Collection and Follow Up Baseline: Age, gender, height, weight, race, APACHE II score, active medical problems at the time of intubation, active comorbidities complicating intubation, mean arterial pressure and vasopressor use prior to intubation, noninvasive ventilator use, highest FIO2 delivered in prior 6 hours, lowest oxygen saturation in prior six hours, ph, PaO2, PaCO2, indication for intubation, reintubation, preoxygenation technique, operator experience, additional personnel available Per- procedural: Date and time of sedative and/or neuromuscular blocker administration, saturation at time of sedative and/or neuromuscular blocker administration, sedative, neuromuscular blocker, ventilation between induction and laryngoscopy, tube characteristics, route, laryngoscope type and size, total number of attempts, tube tape level, confirmation of placement technique, airway grade, airway difficulty, rescue device use, complications 0-6 hours: Post- intubation imaging, post intubation shock or cardiac arrest, SaO2, FIO2, PEEP, and MAP at 1 and 6 hours after intubation.

3 death In- Hospital Outcomes: Date of extubation, date of ICU discharge, date of Treatment Allocation Opaque randomization envelopes will be present in the medical ICU and available to PCCM fellows when it is determined endotracheal intubation will be performed. Randomization will occur in permuted blocks of four to eight and the study personnel along with the operators will be blinded to the randomization assignments prior to the opening of an envelope. Once it has been determined by the treating team that (1) intubation is required, (2) the PCCM fellow will be the first to attempt the procedure, and (3) a specific intubating device or oxygenation strategy is not indicated, the operator will open the envelope and follow the assignment of either direct laryngoscopy or video laryngoscopy for the airway management procedure. Power and Sample Size As previous observational analyses have shown that the success rate of PCCM fellows at direct laryngoscopy is 68% compared to 91% with video laryngoscopy, we will need to randomize 142 airway management events to detect a significant difference in rate of successful first attempt intubation with 90% power. Anticipating a small number of cases in which the primary endpoints may be unavailable due to the emergent circumstances surrounding the procedure, we will prospectively plan to continue the study until a total of 150 airway management events have been included. Consent As direct laryngoscopy and video laryngoscopy are both common in the current practice of endotracheal intubation of critically ill patients, and intubation is so commonly urgent that informed consent is not obtained for the majority of intubations as a part of routine care, a waiver of consent was granted for this study by the institutional review board at Vanderbilt. Statistical analysis Analysis principles Primary analysis will be conducted on an intention- to- treat basis (patients who have protocol violations are analyzed per the assigned treatment arm). All hypothesis tests will be two sided, with an α of 0.05 unless otherwise specified. All analyses are unadjusted unless otherwise specified. Subgroup analyses will be performed irrespective of treatment efficacy. Trial profile

4 We will present a Consolidated Standards of Reporting Trials diagram as Figure 1 to detail the movement of patients through the study. This diagram will include total patients screened, number who met inclusion and exclusion criteria, number enrolled and randomized in the study, number followed, and number analyzed. Baseline comparisons and assessment of randomization To assess randomization success, we will summarize in Table 1 the distribution of baseline variables across the study arms. Categorical variables will be reported as frequencies and percentages and continuous variables as either means with SDs or medians with interquartile ranges. Variables reported will include Demographics (age, gender, race, BMI, ); Indication for intubation; Reintubation status; Active illnesses at the time of intubation; Severity of Illness (APACHE II score); Active comorbidities complicating intubation (vomiting, upper GI bleeding, etc); Respiratory status pre- intubation (NIV use, lowest O2 saturation, FiO2); Airway management procedure (Preoxygenation technique, Saturation at time of induction, Induction medication, Neuromuscular blocker, Laryngoscope type, operator experience with laryngoscope type) Primary Analysis Adjusted test of treatment effect We will test the hypothesis that video laryngoscopy is superior to direct laryngoscopy by comparing the rate of first attempt success between groups after adjustment for the number of times the operator has used the assigned device at the time of intubation. The primary outcome of successful first attempt endotracheal intubation will be analyzed with logistic regression with the assigned device and previous experience with that device as the independent variables and the successful first attempt intubation as the dependent variable. All other comparisons will be considered secondary analyses. Secondary Analyses Analysis of Secondary Outcomes (1) We will test the hypothesis that video laryngoscopy results in a higher rate of successful first attempt intubation compared with direct laryngoscopy in an adjusted analysis using these categorical variables in a Fischer s exact test. (2) VL and DL will also be compared using the continuous variable of time to successful intubation using a Mann- Whitney U test. (3) VL and DL will be compared using the continuous variable of number of attempts to achieve successful intubation using a Mann- Whitney U test. (4) VL and DL will be compared in regards to the need for a second operator to achieve endotracheal intubation using these categorical variables in a Fischer s exact test. (5) We will test the impact of VL and DL on the following safety outcomes by comparing the following endpoints between the two randomized groups using the respective statistical methods: Grade of view on first attempt (Mann- Whitney U

5 test), Incidence of need for additional intubating equipment (Fischer s exact test), incidence of non- hypoxia complications composite of all other recorded complications (Fisher s exact test), incidence of post- intubation tube malposition on CXR (Fisher s exact test) Analysis of Tertiary Outcomes We will assess the impact of VL versus DL on in- hospital mortality using Fisher exact testing. We will assess the impact of VL versus DL on VFDs and ICU- free days using Mann- Whitney U testing. Subgroup Analyses We will repeat the intention- to- treat comparison of patients randomized to video laryngoscopy compared with direct laryngoscopy with respect to the outcome of successful first attempt intubation using the Fisher Exact test in the following subgroups: Subgroups available at procedure initiation 1. BMI No paralysis received 3. Operator experience < 10 previous uses of the device Subgroups related to procedural performance 1. Apneic oxygenation received 2. Grade III- IV view 3. Moderate or difficult airway 4. Duration of airway management above the median 5. Number of attempts required for endotracheal tube placement Modeling to Examine Potential Confounding Factors We will fit a logistic regression model for the primary outcome of successful first attempt intubation in which the variable of randomized group assignment (VL versus DL) will be accompanied by potential baseline confounders including age, BMI, APACHE II score, shock, and operator experience. Modeling to Examine Potential Interactions We will fit a logistic regression model with the above covariates and will sequentially add an interaction term between randomized study group (VL versus DL) and each of the subgrouping variables defined above. Missing Data The design of the study will not produce any missing data in regards to the successful first attempt at endotracheal intubation. Conclusion

6 We describe, before any data unblinding, our approach to analyzing the data from the FELLOW study. We anticipate that this pre- specified framework will enhance the utility of the reported result and allow readers to better judge the impact.