Out-of-hospital hypertonic resuscitation following severe traumatic brain injury

A randomized controlled trial

Eileen M. Bulger, Susanne May, Karen J. Brasel, Martin Schreiber, Jeffrey D. Kerby, Samuel A. Tisherman, Craig Newgard, Arthur Slutsky, Raul Coimbra, Scott Emerson, Joseph P. Minei, Berit Bardarson, Peter Kudenchuk, Andrew Baker, Jim Christenson, Ahamed Idris, Daniel Davis, Timothy C. Fabian, Tom P. Aufderheide, Clifton Callaway & 7 others Carolyn Williams, Jane Banek, Christian Vaillancourt, Rardi Van Heest, George Sopko, J. Steven Hata, David B. Hoyt

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

Context: Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). Objective: To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. Design, Setting, and Participants: Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. Intervention: A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting. Main Outcome Measure: Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). Results: The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P=.67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P=.88). Conclusion: Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival. Trial Registration: clinicaltrials.gov Identifier: NCT00316004.

Original languageEnglish (US)
Pages (from-to)1455-1464
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume304
Issue number13
DOIs
StatePublished - Oct 6 2010

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dextran - saline drug combination
Resuscitation
Randomized Controlled Trials
Glasgow Outcome Scale
Nervous System
Shock
Clinical Trials Data Monitoring Committees
Hospital Administration
Medical Futility
Glasgow Coma Scale
Survival
Brain Edema
Wounds and Injuries
Emergency Medical Services
Random Allocation
Traumatic Brain Injury
Dextrans
Perfusion
Placebos
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bulger, E. M., May, S., Brasel, K. J., Schreiber, M., Kerby, J. D., Tisherman, S. A., ... Hoyt, D. B. (2010). Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: A randomized controlled trial. JAMA - Journal of the American Medical Association, 304(13), 1455-1464. https://doi.org/10.1001/jama.2010.1405

Out-of-hospital hypertonic resuscitation following severe traumatic brain injury : A randomized controlled trial. / Bulger, Eileen M.; May, Susanne; Brasel, Karen J.; Schreiber, Martin; Kerby, Jeffrey D.; Tisherman, Samuel A.; Newgard, Craig; Slutsky, Arthur; Coimbra, Raul; Emerson, Scott; Minei, Joseph P.; Bardarson, Berit; Kudenchuk, Peter; Baker, Andrew; Christenson, Jim; Idris, Ahamed; Davis, Daniel; Fabian, Timothy C.; Aufderheide, Tom P.; Callaway, Clifton; Williams, Carolyn; Banek, Jane; Vaillancourt, Christian; Van Heest, Rardi; Sopko, George; Hata, J. Steven; Hoyt, David B.

In: JAMA - Journal of the American Medical Association, Vol. 304, No. 13, 06.10.2010, p. 1455-1464.

Research output: Contribution to journalArticle

Bulger, EM, May, S, Brasel, KJ, Schreiber, M, Kerby, JD, Tisherman, SA, Newgard, C, Slutsky, A, Coimbra, R, Emerson, S, Minei, JP, Bardarson, B, Kudenchuk, P, Baker, A, Christenson, J, Idris, A, Davis, D, Fabian, TC, Aufderheide, TP, Callaway, C, Williams, C, Banek, J, Vaillancourt, C, Van Heest, R, Sopko, G, Hata, JS & Hoyt, DB 2010, 'Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: A randomized controlled trial', JAMA - Journal of the American Medical Association, vol. 304, no. 13, pp. 1455-1464. https://doi.org/10.1001/jama.2010.1405
Bulger, Eileen M. ; May, Susanne ; Brasel, Karen J. ; Schreiber, Martin ; Kerby, Jeffrey D. ; Tisherman, Samuel A. ; Newgard, Craig ; Slutsky, Arthur ; Coimbra, Raul ; Emerson, Scott ; Minei, Joseph P. ; Bardarson, Berit ; Kudenchuk, Peter ; Baker, Andrew ; Christenson, Jim ; Idris, Ahamed ; Davis, Daniel ; Fabian, Timothy C. ; Aufderheide, Tom P. ; Callaway, Clifton ; Williams, Carolyn ; Banek, Jane ; Vaillancourt, Christian ; Van Heest, Rardi ; Sopko, George ; Hata, J. Steven ; Hoyt, David B. / Out-of-hospital hypertonic resuscitation following severe traumatic brain injury : A randomized controlled trial. In: JAMA - Journal of the American Medical Association. 2010 ; Vol. 304, No. 13. pp. 1455-1464.
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abstract = "Context: Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). Objective: To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. Design, Setting, and Participants: Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. Intervention: A single 250-mL bolus of 7.5{\%} saline/6{\%} dextran 70 (hypertonic saline/dextran), 7.5{\%} saline (hypertonic saline), or 0.9{\%} saline (normal saline) initiated in the out-of-hospital setting. Main Outcome Measure: Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). Results: The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85{\%}). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7{\%} vs 51.5{\%}; difference, 2.2{\%} [95{\%} CI, -4.5{\%} to 9.0{\%}]; hypertonic saline vs normal saline: 54.3{\%} vs 51.5{\%}; difference, 2.9{\%} [95{\%} CI, -4.0{\%} to 9.7{\%}]; P=.67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3{\%} with hypertonic saline/dextran, 75.7{\%} with hypertonic saline, and 75.1{\%} with normal saline (P=.88). Conclusion: Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival. Trial Registration: clinicaltrials.gov Identifier: NCT00316004.",
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T1 - Out-of-hospital hypertonic resuscitation following severe traumatic brain injury

T2 - A randomized controlled trial

AU - Bulger, Eileen M.

AU - May, Susanne

AU - Brasel, Karen J.

AU - Schreiber, Martin

AU - Kerby, Jeffrey D.

AU - Tisherman, Samuel A.

AU - Newgard, Craig

AU - Slutsky, Arthur

AU - Coimbra, Raul

AU - Emerson, Scott

AU - Minei, Joseph P.

AU - Bardarson, Berit

AU - Kudenchuk, Peter

AU - Baker, Andrew

AU - Christenson, Jim

AU - Idris, Ahamed

AU - Davis, Daniel

AU - Fabian, Timothy C.

AU - Aufderheide, Tom P.

AU - Callaway, Clifton

AU - Williams, Carolyn

AU - Banek, Jane

AU - Vaillancourt, Christian

AU - Van Heest, Rardi

AU - Sopko, George

AU - Hata, J. Steven

AU - Hoyt, David B.

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N2 - Context: Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). Objective: To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. Design, Setting, and Participants: Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. Intervention: A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting. Main Outcome Measure: Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). Results: The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P=.67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P=.88). Conclusion: Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival. Trial Registration: clinicaltrials.gov Identifier: NCT00316004.

AB - Context: Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). Objective: To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. Design, Setting, and Participants: Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. Intervention: A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting. Main Outcome Measure: Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). Results: The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P=.67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P=.88). Conclusion: Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival. Trial Registration: clinicaltrials.gov Identifier: NCT00316004.

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