Time profiles of arterial lactate concentrations have been proposed as markers for both the degree of physiological derangement during shock and effectiveness of clinical resuscitation, but have not been evaluated for use in short-term experimental protocols. We developed two quantitative mixed models of sequential arterial lactate concentrations to evaluate competing low-volume (<4 mL/kg) battlefield resuscitation therapies in a rat model of acute severe hemorrhagic shock: a simple linear additive model and a nonlinear mechanistic model that described lactate profiles in a continuous trajectory with a defined turning point. Data were obtained during a study evaluating a novel hemoglobin polymer (OxyVita) in a cocktail of hypertonic saline and Hextend as an alternative to standard Hextend. Fluids were either infused by titration to a mean systolic pressure of 60 mmHg or as a single bolus. Parameter estimates derived from both models were assessed for evidence of treatment efficacy and as indicators of short-term survival. A cocktail of hypertonic saline and Hextend was superior to standard Hextend in enhancing survival; however, lactate profiles did not differ between treatments. Regardless of resuscitation regimen, animals surviving to at least 60 min posthemorrhage can be discriminated from nonsurvivors by significantly lower peak lactates (a difference of at least 3 mM; P < 0.001), and all survivors exhibited a decline in lactate with resuscitation. Sequential measurements of lactate over relatively short time frames during resuscitation are of value in assessing both response to resuscitation and short-term mortality.
Departments of *Emergency Medicine, †Physiology, and ‡Biochemistry, and Virginia Commonwealth University Reanimation Engineering Shock Center (VCURES), Virginia Commonwealth University Medical Center, Richmond, Virginia
Received 31 Jul 2007; first review completed 23 Aug 2007; accepted in final form 21 Sep 2007
Address reprint requests to Penny S. Reynolds, PhD, Department of Emergency Medicine, Virginia Commonwealth University Medical Center, 1201 East Marshall St., Richmond, VA 23298-0401. E-mail: firstname.lastname@example.org.
This study was supported by DARPA (contract no. N66001-02-C-8052 to R.W.B.).