Building a better fluid for emergency resuscitation of traumatic brain injury

Bruce A. Crookes, Stephen M. Cohn, Harry Bonet, Elizabeth A. Burton, Jacob Nelson, Matthias Majetschak, Albert J. Varon, Joel M. Linden, Kenneth G. Proctor

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Hextend (HEX) is a colloid solution that is FDA-approved for volume expansion during surgery. ATL-146e is a novel adenosine A2A receptor agonist that has anti-inflammatory, neuroprotective, and coronary vasodilator properties. Three series of experiments were designed to evaluate the therapeutic potential of HEX±ATL-146e for emergency resuscitation from traumatic brain injury (TBI) + hemorrhagic hypotension. Methods: In the first two studies in vivo, anesthetized, ventilated pigs (30-45 kg) received a fluid percussion TBI, 45% arterial hemorrhage, and 30 minutes shock period. In Series 1, resuscitation consisted of unlimited crystalloid (n = 8) or HEX (n = 8) to correct systolic arterial pressure >100 mm Hg and heart rate <100 bpm for the first 60 minutes ("emergency phase"), and then maintain cerebral perfusion pressure (CPP) > 70 mm Hg for 60-240 minutes. In Series 2 (n = 31), resuscitation consisted of a 1 L bolus of HEX + ATL-146e (10 ng/kg/min, n = 10) or HEX +placebo (n = 10) followed by crystalloid to the same endpoints. In Series 3 in vivo, the hemodynamic response evoked by 0, 10, 50, or 100 ng/kg/min ATL-146e was measured before or 60 minutes after HEX resuscitation from 45% hemorrhage. Results: Following TBI+hemorrhage, there were 4/22 deaths in series 1 and 11/31 deaths in series 2. In those alive at 30 minutes, mean arterial pressure, cardiac index, mixed venous O2 saturation, and cerebral venous O2 saturation were all reduced by 40-60%, while heart rate and lactate were increased 2-5 fold. With no resuscitation (n = 2), there was minimal hemodynamic compensation and progressive acidosis. Upon resuscitation, these values corrected but intracranial pressure progressively rose from <5 mm Hg to 15-20 mm Hg. Series 1: With HEX (n = 8) versus crystalloid (n = 8), CPP was less labile, acid/ base was maintained, and the fluid requirement was reduced by 60% (all p < 0.05) Series 2: With ATL-146e (n = 10) versus placebo (n = 10), stroke volume and cardiac output were improved by 40-60%, and the fluid requirement was reduced by 30% (all p < 0.05). Series 3: ATL-146e caused a dose-related increase (p < 0.05) in stroke volume after, but not before, hemorrhage. The effects on preload, afterload, and heart rate were similar before and after hemorrhage. Conclusions: HEX alone is a safe and efficacious low volume alternative to initial crystalloid resuscitation after TBI. An adenosine A2A agonist combined with 1 L of HEX safely and effectively counteracted a decrease in cardiac performance noted after TBI+hemorrhage without causing hypotension or bradycardia.

Original languageEnglish (US)
Pages (from-to)547-554
Number of pages8
JournalJournal of Trauma - Injury, Infection and Critical Care
Issue number3
StatePublished - Sep 1 2004


  • A2A receptor
  • ATL-146e
  • Adenosine
  • Hemorrhagic Shock
  • Hextend Swine

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine


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