Optimal Out-of-Hospital Blood Pressure in Major Traumatic Brain Injury: A Challenge to the Current Understanding of Hypotension

Ann Emerg Med. 2022 Jul;80(1):46-59. doi: 10.1016/j.annemergmed.2022.01.045. Epub 2022 Mar 24.

Abstract

Study objective: Little is known about the out-of-hospital blood pressure ranges associated with optimal outcomes in traumatic brain injuries (TBI). Our objective was to evaluate the associations between out-of-hospital systolic blood pressure (SBP) and multiple hospital outcomes without assuming any predefined thresholds for hypotension, normotension, or hypertension.

Methods: This was a preplanned secondary analysis from the Excellence in Prehospital Injury Care (EPIC) TBI study. Among patients (age ≥10 years) with major TBIs (Barell Matrix type 1 and/or Abbreviated Injury Scale-head severity ≥3) and lowest out-of-hospital SBPs of 40 to 299 mmHg, we utilized generalized additive models to summarize the distributions of various outcomes as smoothed functions of SBP, adjusting for important and significant confounders. The subjects who were enrolled in the study phase after the out-of-hospital TBI guideline implementation were used to validate the models developed from the preimplementation cohort.

Results: Among 12,169 included cases, the mortality model revealed 3 distinct ranges: (1) a monotonically decreasing relationship between SBP and the adjusted probability of death from 40 to 130 mmHg, (2) lowest adjusted mortality from 130 to 180 mmHg, and (3) rapidly increasing mortality above 180 mmHg. A subanalysis of the cohorts with isolated TBIs and multisystem injuries with TBIs revealed SBP mortality patterns that were similar to each other and to that of the main analysis. While the specific SBP ranges varied somewhat for the nonmortality outcomes (hospital length of stay, ICU length of stay, discharge to skilled nursing/inpatient rehabilitation, and hospital charges), the patterns were very similar to that of mortality. In each model, validation was confirmed utilizing the postimplementation cohort.

Conclusion: Optimal adjusted mortality was associated with a surprisingly high SBP range (130 to 180 mmHg). Below this level, there was no point or range of inflection that would indicate a physiologically meaningful threshold for defining hypotension. Nonmortality outcomes showed very similar patterns. These findings highlight how sensitive the injured brain is to compromised perfusion at SBP levels that, heretofore, have been considered adequate or even normal. While the study design does did not allow us to conclude that the currently recommended treatment threshold (<90 mmHg) should be increased, the findings imply that the definition of hypotension in the setting of TBI is too low. Randomized trials evaluating treatment levels significantly higher than 90 mmHg are needed.

Trial registration: ClinicalTrials.gov NCT01339702.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Blood Pressure
  • Brain
  • Brain Injuries, Traumatic* / complications
  • Brain Injuries, Traumatic* / therapy
  • Child
  • Hospitals
  • Humans
  • Hypotension*

Associated data

  • ClinicalTrials.gov/NCT01339702