Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: A randomized, placebo controlled trial

Eileen M. Bulger, Susanne May, Jeffery D. Kerby, Scott Emerson, Ian G. Stiell, Martin Schreiber, Karen Brasel, Samuel A. Tisherman, Raul Coimbra, Sandro Rizoli, Joseph P. Minei, J. Steven Hata, George Sopko, David C. Evans, David B. Hoyt

    Research output: Contribution to journalArticle

    180 Citations (Scopus)

    Abstract

    Objective: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results: A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95% confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10% (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P <0.01]. Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trial Registration: Clinical Trials.gov, NCT00316017.

    Original languageEnglish (US)
    Pages (from-to)431-441
    Number of pages11
    JournalAnnals of Surgery
    Volume253
    Issue number3
    DOIs
    StatePublished - Mar 2011

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    dextran - saline drug combination
    Traumatic Shock
    Resuscitation
    Shock
    Randomized Controlled Trials
    Placebos
    Confidence Intervals
    Blood Pressure
    Survival
    Wounds and Injuries
    Clinical Trials Data Monitoring Committees
    Clinical Trials
    Hospital Administration
    Medical Futility
    Hemorrhagic Shock
    Mortality
    Emergency Medical Services
    North America
    Dextrans
    Blood Transfusion

    ASJC Scopus subject areas

    • Surgery

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    Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock : A randomized, placebo controlled trial. / Bulger, Eileen M.; May, Susanne; Kerby, Jeffery D.; Emerson, Scott; Stiell, Ian G.; Schreiber, Martin; Brasel, Karen; Tisherman, Samuel A.; Coimbra, Raul; Rizoli, Sandro; Minei, Joseph P.; Hata, J. Steven; Sopko, George; Evans, David C.; Hoyt, David B.

    In: Annals of Surgery, Vol. 253, No. 3, 03.2011, p. 431-441.

    Research output: Contribution to journalArticle

    Bulger, EM, May, S, Kerby, JD, Emerson, S, Stiell, IG, Schreiber, M, Brasel, K, Tisherman, SA, Coimbra, R, Rizoli, S, Minei, JP, Hata, JS, Sopko, G, Evans, DC & Hoyt, DB 2011, 'Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: A randomized, placebo controlled trial', Annals of Surgery, vol. 253, no. 3, pp. 431-441. https://doi.org/10.1097/SLA.0b013e3181fcdb22
    Bulger, Eileen M. ; May, Susanne ; Kerby, Jeffery D. ; Emerson, Scott ; Stiell, Ian G. ; Schreiber, Martin ; Brasel, Karen ; Tisherman, Samuel A. ; Coimbra, Raul ; Rizoli, Sandro ; Minei, Joseph P. ; Hata, J. Steven ; Sopko, George ; Evans, David C. ; Hoyt, David B. / Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock : A randomized, placebo controlled trial. In: Annals of Surgery. 2011 ; Vol. 253, No. 3. pp. 431-441.
    @article{8001f38effae4d3dbe0e6150a29cb52d,
    title = "Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: A randomized, placebo controlled trial",
    abstract = "Objective: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5{\%} saline per 6{\%} dextran 70 (hypertonic saline/dextran, HSD), 7.5{\%} saline (hypertonic saline, HS), or 0.9{\%} saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23{\%} of proposed sample size) for futility and potential safety concern. Results: A total of 853 treated patients were enrolled, among whom 62{\%} were with blunt trauma, 38{\%} with penetrating. There was no difference in 28-day survival-HSD: 74.5{\%} (0.1; 95{\%} confidence interval [CI], -7.5 to 7.8); HS: 73.0{\%} (-1.4; 95{\%} CI, -8.7-6.0); and NS: 74.4{\%}, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10{\%} (5.2; 95{\%} CI, 0.4-10.1); HS: 12.2{\%} (7.4; 95{\%} CI, 2.5-12.2); and NS: 4.8{\%}, P <0.01]. Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trial Registration: Clinical Trials.gov, NCT00316017.",
    author = "Bulger, {Eileen M.} and Susanne May and Kerby, {Jeffery D.} and Scott Emerson and Stiell, {Ian G.} and Martin Schreiber and Karen Brasel and Tisherman, {Samuel A.} and Raul Coimbra and Sandro Rizoli and Minei, {Joseph P.} and Hata, {J. Steven} and George Sopko and Evans, {David C.} and Hoyt, {David B.}",
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    T1 - Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock

    T2 - A randomized, placebo controlled trial

    AU - Bulger, Eileen M.

    AU - May, Susanne

    AU - Kerby, Jeffery D.

    AU - Emerson, Scott

    AU - Stiell, Ian G.

    AU - Schreiber, Martin

    AU - Brasel, Karen

    AU - Tisherman, Samuel A.

    AU - Coimbra, Raul

    AU - Rizoli, Sandro

    AU - Minei, Joseph P.

    AU - Hata, J. Steven

    AU - Sopko, George

    AU - Evans, David C.

    AU - Hoyt, David B.

    PY - 2011/3

    Y1 - 2011/3

    N2 - Objective: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results: A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95% confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10% (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P <0.01]. Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trial Registration: Clinical Trials.gov, NCT00316017.

    AB - Objective: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results: A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95% confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10% (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P <0.01]. Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trial Registration: Clinical Trials.gov, NCT00316017.

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