Independent contributions of hypothermia and acidosis to coagulopathy in swine

BACKGROUND: Clinical coagulopathy occurs frequently in the presence of acidosis and hypothermia. The purpose of this study was to determine the relative contributions of acidosis and hypothermia to coagulopathy, as measured by current standard bedside and clinical laboratory analyses (i.e., bleeding time and prothrombin time). In addition, we investigated possible mechanisms of these effects using a modified prothrombin time test, thromboelastography, and thrombin kinetics analyses. An improved understanding of coagulopathy should facilitate hemorrhage control. METHODS: Twenty-four pigs were randomly allocated into normal (pH, 7.4; 39 degrees C), acidotic (pH, 7.1; 39 degrees C), hypothermic (pH, 7.4; 32 degrees C), and acidotic and hypothermic (pH, 7.1; 32 degrees C) combined groups. Acidosis was induced by the infusion of 0.2N hydrochloric acid in lactated Ringer's solution. Hypothermia was induced by using a blanket with circulating water at 4 degrees C. Development of a clinical coagulopathy was defined as a significant increase in splenic bleeding time. Measurements were compared before (pre) and 10 minutes after (post) the target condition was achieved. RESULTS: Acidosis, hypothermia, or both caused the development of coagulopathy, as indicated by 47%, 57%, and 72% increases in splenic bleeding time (p < 0.05, pre vs. post). Plasma fibrinogen concentration was decreased by 18% and 17% in the acidotic and combined groups, respectively, but not in the hypothermic group. Hypothermia caused a delay in the onset of thrombin generation, whereas acidosis primarily caused a decrease in thrombin generation rates. At 4 minutes' quench time, thrombin generation in the acidotic, hypothermic, and combined groups were 47.0%, 12.5%, and 5.7%, respectively, of the value in the control group. There were no changes in serum tumor necrosis factor-alpha and interleukin-6 in any group during the study. CONCLUSION: Acidosis and hypothermia cause a clinical coagulopathy with different thrombin generation kinetics. These results confirm the need to prevent or correct hypothermia and acidosis and indicate the need for improved techniques to monitor coagulopathy in the trauma population.     

Use of recombinant activated factor VII to treat the acquired coagulopathy of trauma

Recombinant activated factor VII (rFVIIa) is a drug commonly utilized in the treatment of patients with hemophilia and inhibitors. However, its use in previously normal patients with an acquired coagulopathy after trauma and surgery is increasing. Multiple trauma case reports and several case series are available, lending support for the efficacy of the drug in reversing the coagulopathy of trauma. Data from six large animal studies evaluating the efficacy in trauma models are available for evaluation. A single prospective randomized study in elective surgery has recently been published, documenting reduced blood loss and decreased transfusion after a single preoperative dose. This review describes those studies and reiterates the need for well designed prospective randomized human trauma studies.     

Modeling insulin action for development of a closed-loop artificial pancreas

Three models of glucose homeostasis are compared in terms of their steady-state dose-response characteristics, how they characterize glucose distribution kinetics, and how they characterize the dynamics of insulin action. The three models [minimal model, AIDA (Automated Insulin Dosage Advisor), and a model by Sorensen] are used to discuss a wider variety of questions related to metabolic modeling. Simulations are performed comparing each model's response to an intravenous glucose tolerance test, with and without incremental insulin responses, to existing data in individuals with type 1 diabetes mellitus. Predicted changes in blood glucose following a subcutaneous bolus of insulin or an incremental increase in basal insulin delivery are simulated. From these results, the models are evaluated as potential candidates for simulating changes in treatment and developing a closed-loop insulin delivery algorithm. While no consensus model is proposed, relevant issues needing to be addressed are highlighted.     

Electrophysiological dissociation of picture versus word encoding: the distinctiveness heuristic as a retrieval orientation

Event-related potentials (ERPs) were used to investigate the neural processes underlying the distinctiveness heuristic-a response mode in which participants expect to remember vivid details of an experience and make recognition decisions based on this metacognitive expectation. One group of participants studied pictures and auditory words; another group studied visual and auditory words. Studied and novel items were presented at test as words only, with all novel items repeating after varying lags. ERP differences were seen between the word and picture groups for both studied and novel items. For the novel items, ERP differences were largest in frontal and central midline electrodes. In separate analyses, the picture group showed the greatest ERP differences between item types in a parietally based component from 550 to 1000 msec, whereas the word group showed the greatest differences in a frontally based component from 1000 to 2000 msec. The authors suggest that the distinctiveness heuristic is a retrieval orientation that facilitates reliance upon recollection to differentiate between item types. Although the picture group can use this heuristic and its retrieval orientation on the basis of recollection, the word group must engage additional postretrieval processes to distinguish between item types, reflecting the use of a different retrieval orientation.     

Functional effects of single dose first- and second-generation antipsychotic administration in subjects with schizophrenia

Using PET with (15)O water, we characterized the time course of functional brain changes following the acute administration of a first- and a second-generation antipsychotic. Volunteers with schizophrenia were scanned while drug-free (baseline) and after single dose administration of haloperidol (n=6) or olanzapine (n=6) during a time course adapted to their plasma kinetics. To obtain brain location information, we contrasted each post-drug scan to baseline-acquired scans. We plotted the regional cerebral blood flow (rCBF) extracted in these locations and calculated the kinetic characteristics of the curves. Further, we compared and contrasted the rCBF changes induced by the drugs over the first 4 h post-drug administration. Dorsal and ventral striatum, thalamus and anterior cingulate cortex were activated with haloperidol, while frontal, temporal and cerebellum regions evidenced reduced flow. With olanzapine, ventral striatum, anterior cingulate and temporal cortices evidenced increases, and thalamus and lingual cortex decreases, in rCBF. Both drugs activated the caudate nucleus. Haloperidol induced greater activation of the dorsal striatum than did olanzapine. These data reveal important differences in patterns of brain activation between the drugs. Differences in the involvement in basal ganglia parallel known differences between the drugs in the emergence of acute EPS upon emergency administration.     

Evaluation of commercially available fluid-warming devices for use in forward surgical and combat areas

The fluid-warming capabilities of four individual fluid warmers, i.e., Level 1, FMS 2000, Thermal Angel, and Ranger, were compared to evaluate their potential for medical use in forward military echelons of care. Lactated Ringer's solution (LR) and Hextend at room temperature (20 degrees C) or refrigerated temperature (4-7 degrees C) and packed red blood cells at 4 degrees C to 7 degrees C were used with each warmer at two different flow rates. The FMS 2000 consistently warmed all fluids to approximately 37 degrees C, regardless of the starting temperature or flow rate. The Level 1 and Ranger also efficiently warmed all fluids except cold LR to approximately 37 degrees C. The Thermal Angel generally warmed room temperature fluid, cold Hextend, and packed red blood cells to at least 33 degrees C to 34 degrees C but could not warm cold LR. The clinical standard is to have fluids warmed to 32 degrees C at a minimum and more preferably to 34 degrees C to 35 degrees C. Of the fluid warmers tested, only the Thermal Angel failed to achieve such a temperature in warming cold LR. Data from the present study suggest the Ranger and FMS 2000 to be operationally adaptable to at least echelons 1 and 2, respectively, whereas far-forward use of the Thermal Angel has limitations.     

Treatment of an acquired coagulopathy with recombinant activated factor VII in a damage-control patient

Recombinant activated factor VII is commonly used for the treatment of hemophiliac patients with inhibitors and has been studied for use in trauma. We report the use of recombinant activated factor VII for a male patient who was injured in a motor vehicle accident. We also summarize the animal studies and clinical trials that have been reported.