Optimal Out-of-Hospital Blood Pressure in Major Traumatic Brain Injury: A Challenge to the Current Understanding of Hypotension - 15/06/22
, Chengcheng Hu, PhD a, c, Bentley J. Bobrow, MD d, Bruce Barnhart, MSN, RN a, Vatsal Chikani, MPH e, Joshua B. Gaither, MD a, b, Kurt R. Denninghoff, MD a, b, Gail H. Bradley, MD b, e, Amber D. Rice, MD a, b, Jeffrey T. Howard, PhD f, Samuel M. Keim, MD a, bAbstract |
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.
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| Supervising editor: Theodore R. Delbridge, MD, MPH. Specific detailed information about possible conflict of interest for individual editors is available at editors. |
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| Author contributions: CH and DWS had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. DWS drafted and submitted the manuscript, and all authors contributed substantially to its revision. DWS takes responsibility for the paper as a whole. |
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| All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. |
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| Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The University of Arizona received funding from the NIH and DOD supporting the EPIC study. This includes support for the following authors from their academic appointments: DWS, CH, BJB, VC, BB, JBG, and KRD. GHB, ADR, JTH, and SMK have no conflicts of interest to report. Supported by the US Army Medical Research and Materiel Command under Contract No. W81XWH-19-C-0058. The data collection and linkage for the original EPIC study, from which the EPIC Database came, were funded, in part, by a grant from the National Institutes of Health (NIH/NINDS Grant # 1R01NS071049). |
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| The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Furthermore, the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. |
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| Neither the DOD nor the NIH had any role in the following: (1) design and conduct of the study, (2) collection, management, analysis, and interpretation of the data, (3) preparation, review, or approval of the manuscript, or (4) the decision to submit the manuscript for publication. |
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| Trial registration number: NCT01339702. |
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| Presented, in part, at the Annual Scientific Assembly of the National Association of EMS Physicians, January 13 to 16, 2021. |
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