1. Review title. Ketamine as an induction agent for endotracheal intubation in critically ill patients: a systematic review and meta-analysis 2. Original language title. Not applicable 3. Anticipated or actual start date. March 1, 2023 4. Anticipated completion date. July 31, 2023 5. Stage of review at time of this submission. Review stage Started Completed Preliminary searches: Started, not completed Piloting of the study selection process: Started, not completed Formal screening of search results against eligibility criteria: not started Data extraction: not started Risk of bias (quality) assessment: not started Data analysis: not started 6. Named contact. Yuki Kotani 7. Named contact email. kotani.yuki@kameda.jp 8. Named contact address. Department of Intensive Care Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. 9. Named contact phone number. +81-4-7092-2211 10. Organisational affiliation of the review. Department of Intensive Care Medicine, Kameda Medical Center 11. Review team members and their organisational affiliations. Yuki Kotani, Department of Intensive Care Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. kotani.yuki@kameda.jp Takatoshi Koroki, Department of Intensive Care,Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. koroki.takatoshi@kameda.jp Takahiko Yaguchi, Department of Intensive Care,Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. takahiko.yaguchi@kameda.jp Taisuke Shibata, Department of Intensive Care,Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. shibata.taisuke@kameda.jp Motoki Fujii, Department of Intensive Care,Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. fujii.motoki@kameda.jp Mayuko Tonai, Department of Intensive Care,Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. tonai.mayuko@kameda.jp Toshiyuki Karumai, Department of Intensive Care,Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. karumai.toshiyuki@kameda.jp Yoshiro Hayashi, Department of Intensive Care,Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan. hayashi.yoshiro@kameda.jp Giovanni Landoni, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Italy. landoni.giovanni@hsr.it Stefano Fresilli, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Italy. fresilli.stefano@hsr.it Todd C. Lee, Department of Medicine, McGill University, Canada. todd.lee@mcgill.ca 12. Funding sources/sponsors. None 13. Conflicts of interest. None 14. Collaborators. Not applicable 15. Review question. Population: Critically ill patients requiring emergency endotracheal intubation Intervention: Ketamine Control: Any comparator Outcome: Mortality at the main timepoint defined by trial authors Study design: Randomized controlled trials and non-randomized matched studies 16. Searches. Two investigators will independently search PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for eligible articles. To reduce the possibility of missed studies, we will examine the reference lists of included manuscripts and contact subject experts. 17. URL to search strategy. Not applicable 18. Condition or domain being studied. Critical illness 19. Participants/population. Inclusion: Adult critically ill patients undergoing emergency endotracheal intubation for critical illness Exclusion: Pediatric patients 20. Intervention(s), exposure(s). Ketamine as an induction agent for endotracheal intubation We will exclude ketamine infusion for indications other than induction for intubation (e.g., procedural sedation). 21. Comparator(s)/control. Any other intravenous induction agent used for endotracheal intubation in this population 22. Types of study to be included. Inclusion criteria: randomized controlled trials, propensity- and case-matching studies Exclusion criteria: systematic reviews, commentaries/editorials and literature reviews (references will be checked) 23. Context.Studies on acute care settings requiring emergency endotracheal intubation for critical illness. 24. Main outcome(s). Mortality at the longest follow-up available. * Measures of effect: relative risk with 95% credible interval 25. Additional outcome(s). Sequential organ failure assessment score at the longest follow-up available (up to seven days after randomization) * Measures of effect For dichotomous outcomes, relative risk and corresponding 95% confidence interval will be calculated. For continuous outcomes, mean difference or standardized mean difference (as appropriate) with corresponding 95% confidence intervals will be calculated. 26. Data extraction (selection and coding). Eligibility assessment will be first performed by two independent investigators at the title/abstract level. Subsequently, the final selection of included articles will be based on the complete manuscripts and performed by two independent investigators, with disagreements solved by consensus. Extracted data will include first author, publication year, country, study design, comparator drug, and the primary and secondary outcome data. 27. Risk of bias (quality) assessment. To assess the risk of bias, we will use Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs and the Risk Of Bias In Non-randomized Studies – of Exposures (ROBINS-E). 28. Strategy for data synthesis. For the main outcome (mortality), we will use a Bayesian random effects meta-analysis on the risk ratio (RR) scale. We will use a weakly informative prior for mu (N~(0,0.71^2)) corresponding to a mean estimate of no difference with 95% probability the estimated effect size will fall between a RR of 0.25 and 4. For the between-study SD parameter (tau), we will use an informative prior based on the predictive distribution derived from hundreds of Cochrane meta-analyses that reported all-cause mortality. Upon model fitting, we will calculate the posterior probabilities of any benefit (RR <1) and of meaningful clinical effect (a priori defined as a 1% absolute risk reduction based on the weighted control event rate by GLMM). If there are a substantial number of studies identified with no events in both groups (e.g., >5% of studies), we will perform a sensitivity analysis using a binomial-normal hierarchical model (BNHM) that does not require continuity corrections in case of zero counts in one or both arms. In that case, the result will be reported as an odds ratio (OR) with 95% credible interval and the probability of any benefit (OR<1). Review Manager 5.4 and R 4.2.2 will be used. 29. Analysis of subgroups or subsets. We will perform the following subgroup/sensitivity analyses: excluding all high risk of bias studies; RCT and observational studies reported separately. 30. Type and method of review. Type of review Cost effectiveness No Diagnostic No Epidemiologic No Individual patient data (IPD) meta-analysis No Intervention Yes Meta-analysis Yes Methodology No Narrative synthesis No Network meta-analysis No Pre-clinical No Prevention No Prognostic No Prospective meta-analysis (PMA) No Review of reviews No Service delivery No Synthesis of qualitative studies No Systematic review No Other No Health area of the review Alcohol/substance misuse/abuse No Blood and immune system No Cancer No Cardiovascular No Care of the elderly No Child health No Complementary therapies No COVID-19 No Crime and justice No Dental No Digestive system No Ear, nose and throat No Education No Endocrine and metabolic disorders No Eye disorders No General interest No Genetics No Health inequalities/health equity No Infections and infestations No International development No Mental health and behavioural conditions No Musculoskeletal No Neurological Yes Nursing No Obstetrics and gynaecology No Oral health No Palliative care No Perioperative care Yes Physiotherapy No Pregnancy and childbirth No Public health (including social determinants of health) No Rehabilitation No Respiratory disorders No Service delivery No Skin disorders No Social care No Surgery No Tropical Medicine No Urological No Wounds, injuries and accidents No Violence and abuse No 31. Language. English 32. Country. Japan 33. Other registration details. Not applicable 34. Reference and/or URL for published protocol. Not applicable 35. Dissemination plans. We will submit the findings of this review to a high-impact factor journal. We will also present them at national and international conferences. Do you intend to publish the review on completion? Yes 36. Keywords. Systematic review; meta-analysis; ketamine; critical illness; intubation; mortality 37. Details of any existing review of the same topic by the same authors. Not applicable 38. Current review status. Review ongoing 39. Any additional information. Not applicable 40. Details of final report/publication(s). Not applicable