Highlights
• In a multicenter retrospective cohort (n=555) of severe traumatic brain injury (TBI) patients receiving prehospital rapid sequence induction (RSI), 19.1% developed postintubation hypotension (SBP <90 mmHg within 10 minutes).
• Overall 30‑day mortality was 30.5%; mortality was 43.4% in the hypotension group versus 27.4% in the nonhypotension group.
• After adjustment, postintubation hypotension was associated with increased 30‑day mortality (AOR 1.70; 95% CI 1.01–2.86). The effect was especially pronounced in isolated severe TBI (AOR 13.55; 95% CI 3.65–61.66).
Background
Secondary brain injury following traumatic brain injury (TBI) is mediated by systemic insults such as hypotension and hypoxia. Avoiding hypotension is a cornerstone of acute TBI care because cerebral perfusion is pressure‑dependent and autoregulation is often impaired after injury. Prehospital airway management — often delivered by helicopter emergency medical services (HEMS) teams using rapid sequence induction (RSI) — is performed to protect the airway and optimize oxygenation, but induction drugs, positive pressure ventilation, and haemodynamic effects of intubation can provoke hypotension. Understanding whether early postintubation hypotension independently worsens outcomes in severe TBI is important for prehospital practice and the design of interventional trials.
Study design
This was a multicenter, retrospective, observational cohort study conducted in the East of England Trauma Network between January 1, 2015, and December 31, 2022. Three HEMS services (East Anglian Air Ambulance, Essex & Herts Air Ambulance, and Magpas Air Ambulance) contributed consecutive patients aged ≥16 years with trauma and severe TBI who received prehospital RSI and were transported to a hospital in the network.
Severe TBI was defined as a Head Abbreviated Injury Scale (AIS) score ≥3. The exposure of interest was postintubation hypotension, predefined as a new systolic blood pressure (SBP) <90 mmHg within 10 minutes after induction of anesthesia. The primary outcome was 30‑day mortality. Analyses adjusted for prespecified confounders such as age, Glasgow Coma Scale (GCS) score, Injury Severity Score (ISS), and the presence of polytrauma.
Key findings
Population characteristics: 555 patients were included (median age 48 years, IQR 29–66; 73.5% male). Nearly all injuries were blunt (98.7%).
Incidence of hypotension: 106 patients (19.1%) developed postintubation hypotension within the first 10 minutes of anesthesia.
Crude outcomes: Overall 30‑day mortality was 30.5% (169/555). Mortality was 43.4% (46/106) in the postintubation hypotension group versus 27.4% (123/449) in the nonhypotension group.
Adjusted analyses: After multivariable adjustment for clinically relevant confounders, postintubation hypotension was associated with higher 30‑day mortality in patients with polytrauma and severe TBI (adjusted odds ratio [AOR] 1.70; 95% CI 1.01–2.86; P = .04).
Isolated TBI subgroup: The association was far stronger in patients with isolated severe TBI: those who developed postintubation hypotension had substantially higher odds of death (AOR 13.55; 95% CI 3.65–61.66; P < .001) compared with patients without hypotension.
Interpretation of effect sizes: The modest adjusted association in the overall cohort (AOR 1.70) reflects the real‑world complexity of prehospital TBI care and competing risks in multiply injured patients. The very large AOR in isolated TBI suggests that when extracranial hemorrhage and physiologic compromise are less prominent, an acute drop in SBP after intubation may have a disproportionately large effect on cerebral perfusion and outcome.
Mechanisms and biological plausibility
Hypotension after induction can arise from multiple mechanisms: induction agent vasodilation, blunted sympathetic tone, myocardial depression, hypovolemia from occult bleeding, and decreased venous return due to positive pressure ventilation. In TBI, cerebral autoregulation is frequently impaired; therefore, any systemic blood pressure reduction can cause critical reductions in cerebral perfusion pressure (CPP), reduce oxygen delivery, exacerbate ischemia, and increase secondary neuronal injury. The stronger association in isolated TBI supports the view that iatrogenic haemodynamic insults — rather than extracranial bleeding — drive much of the excess risk in this subgroup.
Clinical implications
For prehospital clinicians and systems managing severe TBI, the study highlights three actionable considerations:
1) Prevention: Anticipate and mitigate postintubation hypotension. This includes careful pre‑RSI hemodynamic assessment, judicious use of induction agents and dosing (titration, agent selection), consideration of preemptive vasopressors, and early correction of hypovolemia where appropriate.
2) Monitoring: Rapid, frequent blood pressure assessment immediately after induction (noninvasive or invasive when feasible) and a low threshold to intervene with boluses or vasopressors.
3) Systems-level planning: Training, standardized RSI bundles for patients with severe TBI, and protocols for vasopressor availability in HEMS crews. The finding that isolated TBI patients are particularly vulnerable may influence triage and airway decision-making in borderline cases.
Expert commentary and context
The study reinforces longstanding guidance that hypotension is a key modifiable predictor of poor outcome in TBI. The Brain Trauma Foundation emphasizes prevention of hypotension (historically defined as SBP <90 mmHg) and hypoxia as central to early TBI management. Price et al. contribute important contemporary prehospital data showing a measurable and clinically meaningful association between postintubation hypotension and mortality, especially in isolated TBI.
However, observational data cannot prove causality. Residual confounding is possible (for example, unmeasured severity features, timing differences, or underlying cardiovascular comorbidity). The definition of postintubation hypotension used — SBP <90 mmHg within 10 minutes — is pragmatic and clinically relevant, but sensitivity analyses using alternate thresholds and timing windows may help further refine risk. The very large effect size seen in isolated TBI should be interpreted cautiously given the wider CI and smaller subgroup sample size.
Limitations
Key limitations include the retrospective design, potential for unmeasured confounding, single‑regional trauma network data which may limit generalizability to services with different staffing models or patient mixes, and possible variability in BP measurement frequency and technique. The study does not report granular data on induction agents, vasopressor use, fluid resuscitation strategies, or exact timing of interventions after hypotension. These gaps limit the ability to derive precise interventional recommendations from the association alone.
Research recommendations
Price et al. recommend randomized prehospital interventional trials to reduce postintubation hypotension in TBI. Candidate interventions include preemptive vasopressor administration, alternative induction drug strategies (e.g., hemodynamically stable agents or lower dosing), optimized fluid resuscitation strategies, and protocolized RSI bundles versus usual care. Trials should stratify by isolated versus polytrauma TBI, capture time‑resolved hemodynamic data, and include patient‑centered outcomes such as functional status in addition to mortality.
Conclusion
This multicenter cohort study identifies postintubation hypotension after prehospital RSI as an independent predictor of 30‑day mortality in severe TBI, with a particularly dramatic association in isolated TBI. The findings reinforce the clinical priority of preventing hypotension in the peri‑intubation period and justify prospective trials of targeted interventions in the prehospital setting. Meanwhile, pragmatic measures — careful agent selection and dosing, early hemodynamic optimization, immediate monitoring, and availability of vasopressors — represent reasonable steps to reduce the risk of postintubation hypotension in severe TBI patients undergoing prehospital RSI.
Funding and clinicaltrials.gov
Funding: Refer to Price J et al., JAMA Network Open 2025 for the original study funding statement. The present article is an evidence synthesis and interpretation.
ClinicalTrials.gov: No randomized prehospital interventional trials targeting postintubation hypotension in severe TBI were identified in the Price et al. report. The study authors call for randomized trials; investigators and funders should consider pragmatic HEMS‑based designs.
References
1. Price J, Lachowycz K, Major R, et al. Prehospital Postintubation Hypotension and Survival in Severe Traumatic Brain Injury. JAMA Netw Open. 2025 Nov 3;8(11):e2544057. doi:10.1001/jamanetworkopen.2025.44057.
2. Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons. Guidelines for the Management of Severe Traumatic Brain Injury, 4th Edition. Neurosurgery. 2017. (Guideline emphasizing avoidance of hypotension and hypoxia in TBI.)
Further reading and foundational context on prehospital airway management, hemodynamics, and TBI outcomes are available in contemporary trauma and neurocritical care literature.
