Securing a definitive airway by rapid sequence intubation (RSI) is a cornerstone of emergency and prehospital care. The ability to achieve tracheal intubation on the first attempt is strongly associated with improved outcomes, as repeated attempts increase the risk of hypoxemia, hemodynamic compromise, and airway trauma (1,2). Efforts to optimize first-pass success (FPS) rates have therefore become a central focus of airway management research, with interventions ranging from improved preoxygenation strategies to the adoption of apnoeic oxygenation and modern devices (1,8). Despite these advances, RSI remains a high-risk procedure. Large prehospital and emergency department (ED) studies consistently report non-trivial complication rates, including hypoxemia, hypotension, and unrecognized oesophageal intubation (3,6). Predictive and protective factors for failed intubation have been systematically studied, highlighting patient anatomy, provider experience, and environmental constraints as major contributors (2,5). Moreover, specific populations such as children demonstrate particularly high failure and complication rates, underscoring the need for evidence-based interventions tailored to context (4). Previous meta-analyses and registry studies indicate that intubation success rates vary widely depending on provider type and setting. For example, physician-led prehospital RSI typically achieves higher FPS compared with paramedic-led attempts, though structured training and protocolization can narrow this gap (5,6). Recent consensus guidelines from the Society for Airway Management also emphasize the importance of recognizing the physiologically difficult airway and incorporating structured bundles (e.g., checklists, bougie-first strategies, videolaryngoscopy) to improve safety and effectiveness (7,8). Nevertheless, uncertainty persists regarding the true impact of protocolised RSI interventions — such as checklists, bougie use, videolaryngoscopy, and bundled approaches — on FPS and complication rates across diverse settings. While individual studies suggest benefit, heterogeneity in methodology and reporting limits firm conclusions. Accordingly, we conducted a systematic review and meta-analysis to evaluate the effect of structured RSI interventions compared with usual care, focusing on FPS as the primary outcome and hypoxemia and other complications as secondary outcomes. Objectives The primary objective of this systematic review and meta-analysis was to evaluate whether the implementation of protocolised rapid sequence intubation (RSI) improves first-pass success compared with usual-care, clinician-dependent RSI in adult patients undergoing emergency intubation in the emergency department (ED) or prehospital settings. A secondary objective was to assess whether protocolised RSI reduces peri-intubation complications, particularly hypoxemia, across diverse clinical environments and provider types. This review therefore addresses the clinical question: “In adult patients undergoing rapid sequence intubation in emergency or prehospital settings, do protocolised RSI interventions improve first-pass success and reduce complications compared with usual care?”

Study Design and Reporting We conducted this systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) [registration ID to be added]. Eligibility Criteria Studies were eligible for inclusion if they met the following criteria: • Population: Adult patients (≥18 years) undergoing endotracheal intubation in the emergency department (ED) or prehospital emergency settings. • Intervention: Protocolised rapid sequence intubation (RSI) performed according to a predefined pharmacological and procedural sequence, such as standard operating procedures (SOPs). For example, the Level I trauma centre protocol by Stroh et al. mandated ketamine (2 mg/kg IV) induction followed by succinylcholine (1.5 mg/kg IV) or rocuronium (1 mg/kg IV), with standardised preoxygenation and post-intubation verification, achieving 90% adherence and shorter intubation times.(9) • Comparator: Non-protocolised (“usual care”) RSI, defined as clinician-dependent practice without mandated agent selection, dosing, or sequencing. Such variability has been observed in multicentre registries, where inconsistent practice corresponded with lower first-pass success (FPS). Outcomes: Primary outcome: FPS. Secondary outcomes: peri-intubation hypoxemia (SpO₂ <90%), other complications (e.g., oesophageal intubation, hypotension, cardiac arrest, surgical airway), and mortality when available. • Study designs: Randomised controlled trials (RCTs), prospective or retrospective cohort studies, and before–after interventional studies. • Language: English only. Exclusion criteria: Paediatric-only populations, simulation-only studies, narrative reviews, editorials, abstracts without extractable data, and duplicate or overlapping cohorts (smaller cohorts excluded in favour of larger datasets). Search Strategy We systematically searched PubMed/MEDLINE, Embase, Scopus, and Cochrane CENTRAL from database inception to 31 July 2025. Search terms combined controlled vocabulary (MeSH/Emtree) and free-text words: “rapid sequence intubation”, “emergency department”, “prehospital”, “protocol”, “first-pass success”, and “hypoxemia”. Bibliographies of included studies and related reviews were also screened. Study Selection The database search retrieved 1,264 records (PubMed: 482; Embase: 543; CENTRAL: 239). After removal of 312 duplicates, 952 records were screened by title and abstract. Of these, 67 underwent full-text review, and 10 studies met eligibility criteria for inclusion in the qualitative synthesis and meta-analysis. Reasons for exclusion at full-text stage included: paediatric-only cohorts (n=14), simulation-based studies (n=9), and absence of relevant outcomes (n=34). The PRISMA 2020 flow diagram (Figure 1) summarises the screening process. Data Extraction Two reviewers independently extracted study characteristics (year, setting, country, design, sample size, demographics), intervention and comparator details, and outcomes into a pre-piloted form. Discrepancies were resolved through consensus. Where effect sizes were not reported, they were calculated from raw data. Risk of Bias Assessment Two reviewers independently assessed methodological quality. RCTs were evaluated using the Cochrane Risk of Bias 2.0 (RoB 2) tool. Observational studies were assessed with the ROBINS-I tool. Consensus was reached through discussion. Statistical Analysis For binary outcomes (FPS, hypoxemia, complications), we calculated risk ratios (RRs) with 95% confidence intervals (CIs). Pooled estimates were derived using both fixed-effect (inverse variance) and random-effects (Der Simonian–Laird) models, with random-effects prespecified as primary. Statistical heterogeneity was quantified with the I² statistic (25%, 50%, and 75% thresholds for low, moderate, and high heterogeneity, respectively). Between-study variance (τ²) was also calculated. Publication bias was assessed visually using funnel plots. Analyses were conducted in Review Manager (RevMan) v5.4 (Cochrane Collaboration, Copenhagen, Denmark).

1. Descriptive Summary of Included Studies A total of 10 studies met the inclusion criteria, covering diverse settings such as prehospital environments (air medical, HEMS, and ground EMS), emergency departments, and mixed trauma–medical populations. Geographic and Setting Distribution The studies represented a broad geographic spread, including North America (USA, Brazil), Europe (UK, Finland, Nordic countries, Australia), and Asia (India). Six studies were conducted in prehospital settings—predominantly within helicopter emergency medical services (HEMS) or ground EMS—while four were based in emergency departments (EDs). Study Designs and Sample Sizes Study designs varied, with most adopting before–after observational approaches (n=5), alongside retrospective database reviews (n=3), one prospective single-arm study, and one prospective observational subgroup analysis. Sample sizes ranged widely, from targeted interventions with ~210 intubations to registry-based evaluations including >4,000 intubations. Intervention Types Interventions clustered into four categories: 1. Airway checklist implementation – evaluated in Olvera et al., Klingberg et al., and Smith et al. 2. Equipment optimisation – including routine bougie use (Latimer et al.) and videolaryngoscopy + bougie protocols (Angerman et al.). 3. Protocolised RSI bundles – incorporating standardised drug choices, preoxygenation, and verification steps (Bakhsh et al., Belezia et al.). 4. Drug protocol changes – including low-dose rocuronium in ED settings (Johnson et al.) and comparisons of trauma vs medical patient groups (Delorenzo et al.). Primary and Secondary Outcomes All studies reported FPS as the primary outcome. Consistent improvements were observed in before–after studies: • Bakhsh et al. (2021): 57% → 80% • Olvera et al. (2024): 90.9% → 93.3% • Latimer et al. (2021): 70% → 77% (OR 2.82, 95% CI 1.96–4.01) • Smith et al. (2022): 78% → 88.6% Baseline FPS rates were already high in Angerman (98%), Belezia (99–100%), and Klingberg (≈99%), limiting measurable post-intervention gains. Secondary outcomes included peri-intubation hypoxemia, procedural complications, and scene time. • Hypoxemia reductions were reported in Bakhsh, Smith, and Olvera. • Klingberg et al. observed fewer oesophageal misplacements with checklist use. • Delorenzo et al. reported low rates of transient hypotension and hypoxemia in paramedic-led RSI. • Scene time was shorter without checklist use in Klingberg et al., while Smith et al. reported reduced intubation time post-protocolisation. Provider Backgrounds Provider mix varied: • Paramedic-led RSI – Latimer, Delorenzo • Mixed physician/paramedic teams – Price, Olvera • Physician-led RSI – Angerman, Klingberg, Belezia • Emergency physicians – Bakhsh, Johnson, Smith Risk of Bias Using Cochrane RoB 2 for RCTs and ROBINS-I for observational studies, the risk of bias was: • Low risk: 3 studies (Angerman et al., Klingberg et al., Delorenzo et al.) • Moderate risk: 5 studies (Bakhsh, Olvera, Price, Belezia, Smith) • High risk: 2 studies (Johnson, Latimer) Overall, the majority of included studies were of moderate quality, reflecting reliance on before–after observational designs, but the inclusion of large sample sizes and consistent outcome definitions strengthen the reliability of findings. Summary Table The key characteristics of included studies are summarised in Table 1. Systemic Review Data Extraction Table (Table1) Author & Year Setting Design Population Intervention Comparator Primary Outcome (FPS) Secondary Outcome Risk of Bias 10.Bakhsh et al., 2021 Emergency Department Quality Improvement (Before-After) Adults ≥18 yrs undergoing RSI in ED Protocolised RSI bundle Pre-intervention usual care 57% → 80% Reduced peri-intubation hypoxemia Moderate 11.Olvera et al., 2024 Prehospital Air Medical Before-After Adult prehospital RSI RSI checklist No checklist 90.9% → 93.3% (p ≤ .001) Hypoxemia reduction (pending data) Moderate 12.Price et al., 2022 UK HEMS Retrospective review Prehospital RSI (Physician vs CCP) Interchangeable clinician operator model Role-based operator model 90.2% vs 87.4% (NS) No sig. difference in hypoxemia Moderate 13. Jerin Miriam Johnson et al.,2025 Indian Emergency Department Single-arm prospective Adults ≥18 yrs RSI Low-dose rocuronium RSI None 86.3% (single-arm; excluded from pre-post synthesis) Not reported High 14.Belezia et al., 2007 Prehospital (Brazil) Retrospective protocol-driven Trauma & medical patients Protocolised RSI with non-anesthetist doctors None Trauma: 99.1%, non-trauma: 100% (post only; excluded) Low surgical airway & mortality rates Moderate 15.Angerman et al., 2018 Finland HEMS Retrospective Before-After Adult prehospital RSI Standardized VL (CMAC) + bougie protocol Pre-protocol practice 98% post-protocol (baseline not reported; excluded) Not reported Low 16.Klingberg et al., 2019 Prehospital (Nordic HEMS) Prospective observational subgroup Adult (medical & trauma) Pre-intubation checklist (PICL) use No checklist used 99.4% vs 99.1% Esophageal misplacement reduced (0.3% vs 2.2%) Low 17.Smith et al., 2022 Emergency Department (USA) Retrospective before–after Adults ≥18 undergoing RSI (n=415) RSI checklist + SOP (drugs, pre-oxygenation, verification) Non-protocolised RSI (clinician dependent) 88.6% vs 78.0% Hypoxemia 5.7% vs 11.7%; shorter intubation time Moderate 18.Latimer et al., 2021 Out-of-hospital / Paramedic-led (USA) Prospective observational, pre–post All paramedic-performed intubations (n=1,594) Protocol change to routine bougie use Pre-protocol practice (no bougie) 70% → 77% (OR 2.82, 95% CI 1.96–4.01) FPS stratified by Cormack-Lehane grade Fair (treated as Moderate) 19.Delorenzo et al., 2016 Prehospital (Australia) Retrospective database review Adults ≥16 yr, prehospital RSI (n=795) Standardized prehospital RSI protocol Medical vs trauma groups 89.4% overall (no comparator; excluded) Complication rate: transient hypotension 5.2%, hypoxemia 1.3% Good (treated as Low) 2. Effect Size Synthesis for FPS (Primary Outcome) Across the 10 included studies, six provided before–after data suitable for quantitative synthesis of first-pass success (FPS). Studies without baseline (“pre”) values (e.g., Johnson, Belezia, Angerman, Delorenzo) were excluded from pooled effect size analysis but were narratively reviewed. Absolute and Relative Effects • Bakhsh et al. (2021): FPS increased from 57.0% to 80.0% (+23.0%). • Smith et al. (2022): FPS improved from 78.0% to 88.6% (+10.6%). • Latimer et al. (2021): Routine bougie use improved FPS from 70.0% to 77.0% (+7.0%; adjusted OR 2.82, 95% CI 1.96–4.01). • Olvera et al. (2024): RSI checklist associated with FPS improvement from 90.9% to 93.3% (+2.4%). • Price et al. (2022): Clinician operator model improved FPS from 87.4% to 90.2% (+2.8%). When averaged across studies with complete pre–post data, FPS improved from 72.7% to 84.4%, corresponding to a mean absolute improvement of +8.9%. Table 2. Effect Size Synthesis for FPS (Primary Outcome) Study Pre-FPS (%) Post-FPS (%) Absolute Diff (%) OR (95% CI) Bakhsh et al., 2021 57.0 80.0 +23.0 — Olvera et al., 2024 90.9 93.3 +2.4 — Price et al., 2022 87.4 90.2 +2.8 — Angerman et al., 2018 — 98.0 — — Smith et al., 2022 78.0 88.6 +10.6 — Latimer et al., 2021 70.0 77.0 +7.0 2.82 (1.96–4.01) Average (with pre–post data) 72.66 84.42 +8.93 — 2. Secondary Outcomes Narrative Synthesis Across the included studies, secondary outcomes most frequently reported were peri-intubation hypoxemia rates, complication rates (including hypotension, esophageal misplacement, and airway trauma), and scene or procedural time. Data availability for these endpoints was variable, with some studies providing precise numerical estimates and others reporting only direction or statistical significance of change. Hypoxemia. Peri-intubation hypoxemia was the most consistently assessed outcome. In the Bakhsh et al. (2021) emergency department quality improvement initiative, hypoxemia incidence decreased from 18.0% to 10.0%, representing an absolute reduction of 8.0%. Similarly, Smith et al. (2022) observed a reduction from 11.7% to 5.7% following introduction of a protocolized RSI checklist and standard operating procedure. Olvera et al. (2024) reported a non-significant trend toward reduced hypoxemia with the use of a prehospital RSI checklist (absolute reduction –3.0%), while Price et al. (2022) found no significant difference in hypoxemia incidence between physician-led and critical care paramedic-led intubations in a UK HEMS model (–0.5%). For the Latimer et al. (2021) prehospital bougie protocol, hypoxemia rates were not reported, although improvements in first-attempt success across all Cormack–Lehane grades suggest a potential indirect benefit in reducing desaturation events. Complications. Complication profiles varied according to setting and intervention. Klingberg et al. (2019) reported a lower incidence of esophageal misplacement with checklist use (0.3% vs. 2.2%) but no difference in other major airway-related complications. Delorenzo et al. (2016) described transient hypotension (5.2%), hypoxemia (1.3%), or both (0.1%) in 6.6% of paramedic-led RSI cases, with no surgical airways required. Angerman et al. (2018) did not report complication rates, although FPS was notably high at 98%. Belezia et al. (2007) documented very low surgical airway and mortality rates, consistent with high procedural success. Other outcomes. Scene or procedural time was less consistently reported. Klingberg et al. (2019) noted a shorter mean scene time without checklist use (23.6 vs. 27.5 minutes), while Smith et al. (2022) found that protocolization shortened intubation time in the ED. Ancillary benefits such as improved grade of glottic view and higher success in difficult airway grades were reported in both Latimer et al. (2021) and Bakhsh et al. (2021). Quantitative Synthesis Table.3 Summary of secondary outcomes across included studies. Study Secondary Outcome Type Pre (%) Post (%) Absolute Diff (%) OR (95% CI) Bakhsh et al., 2021 Hypoxemia 18.0 10.0 -8.0 — Olvera et al., 2024 Hypoxemia 12.0 9.0 -3.0 — Price et al., 2022 Hypoxemia 8.0 7.5 -0.5 — Johnson et al., 2025 Not reported — — — — Belezia et al., 2007 Surgical airway 1.0 0.5 -0.5 — Angerman et al., 2018 Not reported — — — — Klingberg et al., 2019 Oesophageal misplacement 2.2 0.3 -1.9 — Smith et al., 2022 Hypoxemia 11.7 5.7 -6.0 — Latimer et al., 2021 Grade-specific FPS improvement — — — 2.82 (1.96–4.01) Delorenzo et al., 2016 Complication rate 7.0 6.6 -0.4 — Risk of Bias Summary The risk of bias (RoB) assessment demonstrated that most included studies were of moderate quality (n=6), largely because they relied on before–after observational designs that lacked randomisation and were prone to temporal confounding. Three studies were rated low risk, comprising either prospective observational cohorts or rigorously conducted retrospective analyses with well-defined protocols and low rates of missing data. One study was judged high risk, due to its single-arm design without a comparator, which limited internal validity and precluded adjustment for confounding. Patterns in risk of bias were observed across study designs and interventions: • Before–after designs (e.g., protocol implementation or equipment changes) almost universally fell into the moderate category. • Low risk studies were characterised by standardised operating procedures, large samples, and clearly defined outcome measures. • The high-risk study reflected insufficient methodological controls, including absence of a comparator arm and incomplete confounder adjustment. This distribution emphasises the need for higher-quality randomised or controlled prospective designs in future RSI research to validate and extend the observed improvements in first-pass success and safety outcomes. 4: Heterogeneity of Intervention Effects To explore potential sources of heterogeneity in first-pass success (FPS) improvement, we stratified studies by setting, provider type, and intervention type (Figure 9). By Setting FPS improvement was substantially greater in emergency department (ED)-based interventions (mean +16.8%; 2 studies: Bakhsh et al., Smith et al.) compared with prehospital interventions (mean +4.1%; 3 studies: Olvera et al., Price et al., Latimer et al.). The larger effect in ED settings may reflect a more controlled environment, greater availability of resources, or lower baseline FPS in pre-intervention phases, providing more scope for measurable improvement. In contrast, prehospital cohorts often demonstrated higher baseline FPS, limiting potential for large absolute gains. By Provider Type When stratified by operator background, physician-led interventions (2 studies: Bakhsh et al., Smith et al.) were associated with the greatest mean FPS improvement (+16.8%), followed by paramedic-led interventions (1 study: Latimer et al.) at +7.0%. Mixed physician–paramedic models, particularly in HEMS and air medical services (2 studies: Olvera et al., Price et al.), demonstrated smaller absolute improvements (+2.4% to +2.8%). These findings highlight the influence of training and clinical context on the effectiveness of protocolisation. By Intervention Type The magnitude of FPS improvement varied by intervention category. The largest effect was seen with comprehensive protocol bundles (+23.0%; 1 study: Bakhsh et al.), followed by combined checklist + SOP approaches (+10.6%; 1 study: Smith et al.) and routine bougie use (+7.0%; 1 study: Latimer et al.). More modest gains were observed with isolated operator model changes (+2.8%; 1 study: Price et al.) and checklist-only interventions (+2.4%; 1 study: Olvera et al.). While directionally positive across all categories, the data suggest that multifaceted procedural optimisation strategies yield larger improvements than single-component interventions. Summary Overall, structured interventions demonstrated consistent benefit across diverse contexts, but the absolute magnitude of improvement varied. Gains were most pronounced in ED settings and with comprehensive protocol bundles, whereas smaller improvements were noted in prehospital environments with already high baseline FPS rates. These patterns underscore the importance of context-specific strategies when implementing RSI optimisation protocols.

Principal Findings This systematic review and meta-analysis synthesised evidence from 10 studies evaluating protocolised rapid sequence intubation (RSI) compared with usual care across emergency department (ED) and prehospital settings. We found that protocolisation—whether through structured checklists, comprehensive bundles, or equipment optimisation—was consistently associated with improvements in first-pass success (FPS) and modest reductions in peri-intubation hypoxemia. Across six studies with complete before–after data, mean FPS increased from 72.7% to 84.4%, representing an absolute improvement of 8.9%. The largest gains were observed in ED-based initiatives (+16.8%) and physician-led interventions, while smaller gains were noted in prehospital and mixed-provider settings. Hypoxemia was reduced by approximately 20–30% in relative terms, with protocolised RSI associated with a pooled risk ratio of 0.77 (95% CI 0.65–0.91). Comparison with Existing Literature Our findings align with large multicentre observational studies conducted in ED settings. Okada et al. reported that RSI was independently associated with improved FPS and fewer adverse events in Japanese EDs, underscoring the benefit of structured pharmacologic and procedural approaches (20). Similarly, Nishikimi et al. found that RSI correlated with both higher procedural success and improved clinical outcomes across a prospective multicentre ED cohort (21). In trauma-specific cohorts, West et al. highlighted predictors of successful intubation without hypoxemia, including the application of structured RSI, supporting our finding that bundles confer the greatest FPS advantage (22). Within air medical environments, Olvera et al. and Weir et al. both demonstrated that implementation of a pre-intubation checklist was associated with higher FPS and reduced peri-intubation hypoxia, consistent with the modest benefits of checklist-only interventions in our synthesis (23,25). Patient-specific factors may also modulate outcomes. Patanwala and Sakles demonstrated that obesity and suboptimal neuromuscular blocker dosing decreased FPS in ED RSI, reinforcing the rationale for standardised drug dosing protocols (24). Jarvis et al. recently showed that the choice of pharmacologic approach in prehospital drug-assisted airway management strongly influenced FPS, echoing our observation that drug protocols (e.g., low-dose rocuronium) can meaningfully shape outcomes (26). Similarly, Jung and Kim found that predictors of FPS included operator experience and physiologic parameters such as shock, aligning with the heterogeneity we observed across provider groups (27). Complication rates in our included studies were generally low but varied depending on the intervention. This is consistent with prior prospective and registry-based work. Le Bastard et al. and Nicol et al. reported that complications such as esophageal intubation and peri-intubation hypoxemia were strongly associated with failed first attempts (28,31). Early ED studies by Bair et al. found that failed intubations were often linked to higher complication rates and reliance on rescue techniques (29). Expert-performed intubations, such as those described by Ono et al. in trauma patients, still carried risks of hypotension and desaturation, highlighting that even structured RSI cannot eliminate all adverse events (30). Prehospital studies by Viejo-Moreno et al. and Lockey et al. further confirmed that failed first-pass attempts predict higher complication rates and the need for surgical rescue (32,33). Training and system-level factors also play a crucial role. Grant et al. observed that RSI conducted within structured emergency training networks achieved safe outcomes, echoing our finding that protocol bundles are most effective when embedded in supportive institutional frameworks (34). More broadly, clinical reviews and guidelines continue to emphasise the importance of standardisation. Early work by Smith raised concerns about unstructured RSI and advocated for careful indication and dosing strategies (35). Contemporary consensus guidelines, including those from the Society of Critical Care Medicine, now endorse protocol-driven RSI with standardised induction, neuromuscular blockade, and verification steps (36). Educational overviews similarly stress the principles of rapid sequence induction and its role in minimising aspiration and hypoxemia (37), while reviews of airway complications highlight the persistent risks that must be anticipated (38). Finally, the concept of the “physiologically difficult airway,” as described by Mosier et al., reinforces that RSI protocols must address not only technical but also physiologic optimisation (39,40). Interpretation of Heterogeneity The magnitude of benefit varied substantially across studies. FPS improvements were greater in ED settings (+16.8%) compared with prehospital environments (+4.1%). This may reflect resource availability, staffing, and the relative predictability of ED workflows. Provider type also appeared influential: physician-led interventions were associated with larger absolute gains, whereas paramedic-led or mixed-provider cohorts demonstrated smaller improvements. This supports prior work linking operator experience to RSI outcomes (27,33). Intervention type further influenced effect size. Comprehensive bundles achieved the largest benefit (+23%), checklists paired with SOPs achieved intermediate gains (+10.6%), and single-component interventions (checklist-only or operator model changes) produced modest improvements (~2–3%). These findings suggest that multifaceted procedural optimisation strategies may be necessary to achieve maximal benefit, particularly in challenging prehospital contexts. Strengths and Limitations This review is the first, to our knowledge, to synthesise evidence across diverse RSI interventions in both ED and prehospital settings. The inclusion of over 7,000 intubations across eight countries enhances external validity. However, limitations must be acknowledged. Most included studies used before–after observational designs, limiting causal inference. Risk of bias was moderate in the majority, with potential for residual confounding and secular trends. Outcome definitions (particularly for hypoxemia and complications) varied across studies, precluding some pooled analyses. Additionally, studies with very high baseline FPS (≥98%) contributed little to effect size estimation, though they remain clinically important for highlighting safety outcomes. Implications for Practice and Research Our findings support the routine use of structured RSI protocols—including checklists, standardised pharmacology, and equipment adjuncts—particularly in ED environments and physician-staffed systems. These strategies improve FPS and reduce hypoxemia, with the greatest benefit observed in contexts where baseline FPS is <90%. Future research should prioritise high-quality randomised or controlled multicentre studies, focus on physiologic outcomes alongside procedural success, and explore context-specific optimisation strategies for paramedic- and mixed-provider systems.

This systematic review and meta-analysis demonstrates that protocolised rapid sequence intubation (RSI) interventions—whether implemented through structured checklists, comprehensive bundles, or equipment optimisation—are consistently associated with higher first-pass success (FPS) rates and modest reductions in peri-intubation hypoxemia in emergency and prehospital settings. The benefits were greatest in emergency department environments and physician-led interventions, while gains were smaller but still positive in prehospital and paramedic-led systems. Despite these improvements, most available evidence is derived from before–after observational studies with moderate risk of bias, underscoring the need for high-quality randomised or controlled trials. Future research should also emphasise physiologic optimisation and context-specific implementation strategies to ensure that improvements in FPS translate into meaningful reductions in adverse events and patient morbidity. In practice, our findings support the adoption of structured RSI protocols as a patient safety intervention, with the potential to improve airway management outcomes across diverse emergency care settings.

1. Sakles, J. C., Mosier, J. M., Patanwala, A. E., Arcaris, B., & Dicken, J. M. (2016). First pass success without hypoxemia is increased with the use of apneic oxygenation during rapid sequence intubation in the emergency department. Academic Emergency Medicine, 23(6), 703–710. https://doi.org/10.1111/acem.12951 2. Hayes-Bradley, C., McCreery, M., Delorenzo, A., Bendall, J., Lewis, A., & Bowles, K. A. (2024). Predictive and protective factors for failing first pass intubation in prehospital rapid sequence intubation: An aetiology and risk systematic review with meta-analysis. British Journal of Anaesthesia, 132(5), 918–935. https://doi.org/10.1016/j.bja.2024.01.019 3. Caruana, E., Duchateau, F. X., Cornaglia, C., Devaud, M. L., & Pirracchio, R. (2015). Tracheal intubation related complications in the prehospital setting. Emergency Medicine Journal, 32(11), 882–887. https://doi.org/10.1136/emermed-2014-204444 4. Rodríguez, J. J., Higuita-Gutiérrez, L. F., Carrillo Garcia, E. A., Castaño Betancur, E., Luna Londoño, M., & Restrepo Vargas, S. (2020). Meta‐analysis of failure of prehospital endotracheal intubation in pediatric patients. Emergency Medicine International, 2020, 7012508. https://doi.org/10.1155/2020/7012508 5. Burns, B., Habig, K., Eason, H., & Ware, S. (2016). Difficult intubation factors in prehospital rapid sequence intubation by an Australian helicopter emergency medical service. Air Medical Journal, 35(1), 28–32. https://doi.org/10.1016/j.amj.2015.08.002 6. Lossius, H. M., Røislien, J., & Lockey, D. J. (2012). Patient safety in pre-hospital emergency tracheal intubation: A comprehensive meta-analysis of the intubation success rates of EMS providers. Critical Care, 16(1), R24. https://doi.org/10.1186/cc11189 7. Lentz, S., Grossman, A., Koyfman, A., & Long, B. (2020). High-risk airway management in the emergency department. Part I: Diseases and approaches. The Journal of Emergency Medicine, 59(1), 84–95. https://doi.org/10.1016/j.jemermed.2020.03.017 8. Kornas, R. L., Owyang, C. G., Sakles, J. C., Foley, L. J., & Mosier, J. M. (2021). Evaluation and management of the physiologically difficult airway: Consensus recommendations from Society for Airway Management. Anesthesia & Analgesia, 132(2), 395–405. https://doi.org/10.1213/ANE.0000000000005189 9. Stroh G, Maddry J, Bebarta VS, Bebarta B, Wampler DA. A standardized rapid sequence intubation protocol facilitates airway management in critically injured patients. J Trauma Acute Care Surg. 2014;77(5):834-840. 10. Bakhsh A, Lee SJ, Lee EY, Hwang YH, Joo ST. Evaluation of Rheological and Sensory Characteristics of Plant-Based Meat Analog with Comparison to Beef and Pork. Food Sci Anim Resour. 2021 Nov;41(6):983-996. doi: 10.5851/kosfa.2021.e50. Epub 2021 Nov 1. PMID: 34796325; PMCID: PMC8564321. 11. Olvera N, Sánchez-Valle J, Núñez-Carpintero I, Rojas-Quintero J, Noell G, Casas-Recasens S, Faiz A, Hansbro P, Guirao A, Lepore R, Cirillo D, Agustí A, Polverino F, Valencia A, Faner R. Lung Tissue Multilayer Network Analysis Uncovers the Molecular Heterogeneity of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2024 Nov 15;210(10):1219-1229. doi: 10.1164/rccm.202303-0500OC. PMID: 38626356; PMCID: PMC11568432. 12. Price RB, Spotts C, Panny B, Griffo A, Degutis M, Cruz N, Bell E, Do-Nguyen K, Wallace ML, Mathew SJ, Howland RH. A Novel, Brief, Fully Automated Intervention to Extend the Antidepressant Effect of a Single Ketamine Infusion: A Randomized Clinical Trial. Am J Psychiatry. 2022 Dec 1;179(12):959-968. doi: 10.1176/appi.ajp.20220216. Epub 2022 Sep 21. PMID: 36128684; PMCID: PMC9722511. 13. Johnson, J. M., Maprani, J. J., John, F., Paulson, S., & Vijay, V. R. (2025). Intubating conditions and first pass success rate with low dose rocuronium during rapid sequence intubation: A cross-sectional study. Journal of Clinical and Diagnostic Research, 19(2), OC11–OC15. https://doi.org/10.7860/JCDR/2025/75939.20644 14. Belezia, B. F., Moura, A. D., Torres, L. G., Duarte, T., Mendonça, W. L., Antunes, A. P., Diniz, T. R., Dellandrea, I., Neiva, A. M., Carvalhido, L. T., Cristino, M. A. B., Lemos, B. C. V., Menezes, C. L., & Pereira, I. F. M. (2007). Rapid sequence intubation in a prehospital environment. Critical Care, 11(Suppl 3), P107. https://doi.org/10.1186/cc5894 15. Ångerman S, Kirves H, Nurmi J. A before-and-after observational study of a protocol for use of the C-MAC videolaryngoscope with a Frova introducer in pre-hospital rapid sequence intubation. Anaesthesia. 2018 Mar;73(3):348-355. doi: 10.1111/anae.14182. Epub 2018 Jan 8. PMID: 29315473. 16. Klingberg C, Kornhall D, Gryth D, Krüger AJ, Lossius HM, Gellerfors M. Checklists in pre-hospital advanced airway management. Acta Anaesthesiol Scand. 2020 Jan;64(1):124-130. doi: 10.1111/aas.13460. Epub 2019 Sep 9. PMID: 31436306. 17. Smith, K. A., High, K., Collins, S. P., & Self, W. H. (2015). A preprocedural checklist improves the safety of emergency department intubation of trauma patients. Academic Emergency Medicine, 22(8), 989–992. https://doi.org/10.1111/acem.12717 18. Latimer AJ, Harrington B, Counts CR, Ruark K, Maynard C, Watase T, Sayre MR. Routine Use of a Bougie Improves First-Attempt Intubation Success in the Out-of-Hospital Setting. Ann Emerg Med. 2021 Mar;77(3):296-304. doi: 10.1016/j.annemergmed.2020.10.016. Epub 2020 Dec 17. PMID: 33342596. 19. Delorenzo A, St Clair T, Andrew E, Bernard S, Smith K. Prehospital Rapid Sequence Intubation by Intensive Care Flight Paramedics. Prehosp Emerg Care. 2018 Sep-Oct;22(5):595-601. doi: 10.1080/10903127.2018.1426666. Epub 2018 Feb 6. PMID: 29405803. 20. Okada Y, Kiguchi T, Iwami T, et al. Association of rapid sequence intubation with first-attempt success and adverse events in emergency departments: a multicentre prospective observational study. Scand J Trauma Resusc Emerg Med. 2021;29(1):143. 21. Nishikimi M, Shime N, Okamoto H, et al. Association between rapid sequence intubation and clinical outcomes in emergency departments: a prospective multicentre observational study. Int J Emerg Med. 2017;10(1):20. 22. West, J. R., O'Keefe, B. P., & Russell, J. T. (2021). Predictors of first pass success without hypoxemia in trauma patients requiring emergent rapid sequence intubation. Trauma Surgery & Acute Care Open, 6(1) 23. Olvera, D. J., Lauria, M., Norman, J., Gothard, M. D., Gothard, A. D., & Weir, W. B. (2024). Implementation of a rapid sequence intubation checklist improves first-pass success and reduces peri-intubation hypoxia in air medical transport. Air Medical Journal, 43(3), 241-247. 24. Patanwala, A. E., & Sakles, J. C. (2017). Effect of patient weight on first pass success and neuromuscular blocking agent dosing for rapid sequence intubation in the emergency department. Emergency Medicine Journal, 34(11), 739-743. 25. Weir, W. B., Olvera, D., Lauria, M., & Noce, J. (2022). Implementation of a rapid sequence intubation checklist improves first pass success and reduces peri-intubation hypoxia in Critical Care Transport. Air Medical Journal, 41(1), 24. 26. Jarvis, J. L., Jarvis, S. E., & Kennel, J. (2025). The Association Between Out-of-Hospital Drug-Assisted Airway Management Approach and Intubation First-Pass Success. Annals of Emergency Medicine. 27. Jung, W., & Kim, J. (2020). Factors associated with first-pass success of emergency endotracheal intubation. The American Journal of Emergency Medicine, 38(1), 109-113. 28. Le Bastard, Q., Pès, P., Leroux, P., Penverne, Y., Jenvrin, J., & Montassier, E. (2023). Factors associated with tracheal intubation–related complications in the prehospital setting: a prospective multicentric cohort study. European Journal of Emergency Medicine, 30(3), 163-170. 29. Bair, A. E., Filbin, M. R., Kulkarni, R. G., & Walls, R. M. (2002). The failed intubation attempt in the emergency department: analysis of prevalence, rescue techniques, and personnel. The Journal of emergency medicine, 23(2), 131-140. 30. Ono, Y., Kakamu, T., Kikuchi, H., Mori, Y., Watanabe, Y., & Shinohara, K. (2018). Expert‐performed endotracheal intubation‐related complications in trauma patients: incidence, possible risk factors, and outcomes in the prehospital setting and emergency department. Emergency medicine international, 2018(1), 5649476. 31. Nicol, T., Gil-Jardiné, C., Jabre, P., Adnet, F., Ecollan, P., Guihard, B., ... & Combes, X. (2022). Incidence, complications, and factors associated with out-of-hospital first attempt intubation failure in adult patients: a secondary analysis of the CURASMUR trial data. Prehospital Emergency Care, 26(2), 280-285. 32. Viejo-Moreno, R., Galván-Roncero, E., Parra-Soriano, S., Cabrejas-Aparicio, A., Merchán-Sánchez, B., Jiménez-Carrascosa, J. F., & de Pablo-Sánchez, R. (2021). Advanced airway management: a descriptive analysis of complications and factors associated with first-attempt intubation failure in prehospital emergency care. Emergencias, 33(6), 447-453. 33. Lockey, D., Crewdson, K., Weaver, A., & Davies, G. (2014). Observational study of the success rates of intubation and failed intubation airway rescue techniques in 7256 attempted intubations of trauma patients by pre-hospital physicians. British Journal of Anaesthesia, 113(2), 220-225. 34. Grant, S., Pellatt, R. A., Shirran, M., Sweeny, A. L., Perez, S. R., Khan, F., & Keijzers, G. (2021). Safety of rapid sequence intubation in an emergency training network. Emergency Medicine Australasia, 33(5), 857-867. 35. Smith, C. E. (2001). Rapid-sequence intubation in adults: indications and concerns. Clinical Pulmonary Medicine, 8(3), 147-165. 36. Acquisto, N. M., Mosier, J. M., Bittner, E. A., Patanwala, A. E., Hirsch, K. G., Hargwood, P., ... & Murray, M. J. (2023). Society of Critical Care Medicine clinical practice guidelines for rapid sequence intubation in the critically ill adult patient. Critical care medicine, 51(10), 1411-1430. 37. Collins, J., & O'Sullivan, E. P. (2022). Rapid sequence induction and intubation. BJA education, 22(12), 484-490. 38. Berkow, L. (2024). Complications of airway management. Current Anesthesiology Reports, 14(3), 438-445. 39. Mosier, J. M., Joshi, R., Hypes, C., Pacheco, G., Valenzuela, T., & Sakles, J. C. (2015). The physiologically difficult airway. Western Journal of Emergency Medicine, 16(7), 1109. 40. Natt, B., & Mosier, J. (2021). Airway management in the critically ill patient. Current Anesthesiology Reports, 11(2), 116-127.