Impact Of Hypothermia Research Articles

Moderate hypothermia prevents cardiac arrest-mediated suppression of drug metabolism and induction of interleukin-6 in rats*

Therapeutic hypothermia is being clinically used to reduce neurologic deficits after cardiac arrest (CA). Patients receiving hypothermia after CA receive a wide-array of medications. During hypothermia, drug metabolism is markedly reduced. Little, however, is known about the impact of hypothermia on drug metabolism after rewarming. The objective of this study was to examine the effect of CA and hypothermia on the functional regulation of two major drug metabolizing cytochrome P450 (CYP) isoforms. Laboratory investigation. University pharmacy school and animal research facility. Thirty-six male Sprague-Dawley rats. Hypothermia was induced via surface cooling in a rat CA model and maintained for 3 hrs. Animals were killed at 5 or 24 hrs and liver was analyzed for hepatic activity and mRNA expression of CYP3A2 and CYP2E1. Plasma interleukin-6 (IL-6) concentrations were determined. The effect of IL-6 on pregnane X receptor-mediated transcription of the rat CYP3A2 promoter was evaluated via luciferase reporter in HepG2 cells. At 24 hrs after CA a decrease in CYP3A2 and CYP2E1 activity was observed, 55.7% +/- 12.8% and 46.8% +/- 29.7% of control, respectively (p < 0.01). CA decreased CYP3A2 mRNA (p < 0.05), but not CYP2E1 mRNA. Expression of other pregnane X receptor target enzymes and transporter genes were similarly down-regulated. CA also produced an approximately ten-fold increase in plasma IL-6. CA-mediated inhibition of CYP3A2 and CYP2E1 was attenuated by hypothermia, as was the increase in IL-6. Furthermore, IL-6 attenuated pregnane X receptor-mediated transcription of the CYP3A2 promoter. CA produces CYP3A2 down-regulation at 24 hrs, potentially via IL-6 effects on pregnane X receptor-mediated transcription. Also, hypothermia attenuates the CA-mediated down-regulation, thereby normalizing drug metabolism after rewarming.

Hypothermia for neuroprotection after cardiac arrest: Mechanisms, clinical trials and patient care

Therapeutic hypothermia is a proven part of cardio-cerebral resuscitation after cardiac arrest as it improves neurologic outcomes after hypoxic brain injury. This article reviews the mechanisms of hypothermic neuroprotection, the clinical trials that support its use after cardiac arrest, as well as the impact of hypothermia on patient management and prognosis. In caring for patients suffering hypoxic brain injury after cardiac arrest, the role of the neurologist is no longer limited to prognosis but is now to become actively involved in clinical management which includes the use of therapeutic hypothermia.

Profound Hypothermic Cardiopulmonary Bypass Facilitates Survival Without a High Complication Rate in a Swine Model of Complex Vascular, Splenic, and Colon Injuries

Induction of a profound hypothermia for emergency preservation and resuscitation in severe hemorrhagic shock can improve survival from lethal injuries, but the impact of hypothermia on bleeding and infectious complications has not been completely determined. Uncontrolled hemorrhage was induced in 26 swine (95 to 135 lbs) by creating an iliac artery and vein injury, and 30 minutes later, by lacerating the descending thoracic aorta. Through a left thoracotomy approach, profound total body hypothermia (10 degrees C) was induced (2 degrees C/min) by infusing cold organ preservation solution into the aorta. The experimental groups were: vascular injuries alone (group 1, n=10), vascular and colon injuries (group 2, n=8), and vascular, colon, and splenic injuries (group 3, n=8). All injuries were repaired during 60 minutes of low-flow cardiopulmonary bypass (CPB) with hemodilution and profound hypothermia; then the animals were slowly rewarmed (0.5 degrees C/min) back to normothermia. Survivors were monitored for 6 weeks for postoperative bleeding, neurologic deficits, cognitive function (learning new skills), organ dysfunction, and septic complications. Six-week survival rates were 90% in group 1, 87.5% in group 2, and 75% in group 3 (p > 0.05). One animal in each group died from acute cardiac failure during the early postoperative phase. Splenic salvage was possible in all animals, and none required complete splenectomy for hemorrhage control. All surviving animals were neurologically intact, displayed normal learning capacity, and had no longterm organ dysfunction. None of the animals had postoperative hemorrhage or experienced septic complications. One animal in group 3 died on the ninth postoperative day because of bowel obstruction (volvulus). Induction of profound hypothermia can preserve the viability of key organs during repair of lethal injuries. This strategy can be used even in the presence of solid organ and bowel injuries to improve survival, without any considerable increase in postoperative complication rates.

Impact of Hypothermia on the Response to Neuromuscular Blocking Drugs

Muscle strength is reduced during hypothermia, both in the presence and in the absence of neuromuscular blocking drugs. A 2 degrees C reduction in body temperature may double the duration of neuromuscular blockade. Central body and muscle temperatures decline in parallel, as long as peripheral vasoconstriction does not occur. A reduction in muscle strength must be expected at a body temperature less than 36 degrees C (corresponding to a muscle temperature of approximately 35 degrees C). Local cooling of the hand may make adductor pollicis twitch tension monitoring less useful during clinical anesthesia. The efficacy of neostigmine is maintained during mild hypothermia. The use of a nerve stimulator is strongly recommended to monitor the effect of neuromuscular blocking drugs during intraoperative hypothermia.

The impact of hypothermia on trauma care at the 31st combat support hospital

Background The primary objective of this study was to review the incidence of hypothermia, and its effect on surgical management, resource utilization, and survival at the 31st Combat Support Hospital (CSH). Methods This study was a retrospective analysis of all combat trauma injuries treated at the 31st CSH over a 12-month period. All trauma admissions were included. Descriptive and inferential analysis were performed using SPSS 11.0 software package (SPSS Inc., Chicago, IL). Results A cohort of 2848 patients was identified; 18% were hypothermic (temperature <36°C). Hypothermia was significantly ( P < .05) correlated with admission Glasgow Coma Scale (GCS), tachycardia, hypotension, lower hematocrit, and acidosis. Hypothermic patients had a significantly higher blood product and factor VIIa requirement. Hypothermia was an independent predictor of operative management of injuries, damage control laparotomy, factor VIIa use, and overall mortality ( P < .05). Conclusion Combat trauma patients have a high percentage of penetrating injuries with variable evacuation times. Hypothermia was a pre-hospital physiologic marker, and independent contributor to overall mortality. Prevention of hypothermia could reduce resource utilization and improve survival in the combat setting.

Mild Hypothermia Impairs Left Ventricular Diastolic but Not Systolic Function

Hypothermia is a component of myocardial protection during cardiopulmonary bypass (CPB) and cardioplegic arrest (CA). Patients in the early post CPB period often show mild hypothermia and cardiac dysfunction. We sought to investigate the impact of hypothermia on left ventricular (LV) function. Anesthetized dogs (n = 12) were instrumented with myocardial ultrasonic crystals and LV micromanometer. Systolic function was measured by preload recruitable stroke work (PRSW). Diastolic function was measured by −dP/dtmax and tau. In six dogs (Norm group), body temperature was maintained at baseline levels. In another six dogs (Hypo group), body temperature dropped gradually over the time course of the experiment. The body temperature in the Hypo group decreased from 37.0 ± 0.3°C to 35.2 ± 1.0°C. −dP/dtmax decreased and tau increased significantly with hypothermia but were stable in the Norm group. Both tau and −dP/dtmax showed a linear relationship to the body temperature (r =.91 and r =. 93, respectively). PRSW did not change and cardiac output decreased with hypothermia. Thus, even mild hypothermia impairs LV diastolic but not systolic function. Cardiac output is temperature sensitive and therefore rewarming of patients post-CPB has priority.

Normothermia is protective during infrarenal aortic surgery

Purpose: Mild hypothermia has been suggested to be protective against tissue ischemia during aortic operations. However, recent studies have documented detrimental cardiac effects of hypothermia during a variety of operative procedures. The influence of different warming methods and the impact of hypothermia during standard aortic procedures was assessed. Methods: One hundred patients who underwent repair of infrarenal aortic aneurysms or aortoiliac occlusive disease were prospectively randomized into 2 groups, receiving either a circulating water mattress or a forced air warming blanket. Adjuvant warming methods were standardized. The day before surgery, 48-hour Holter monitors were applied and interpreted by a cardiologist blinded to the treatment. Randomization resulted in equivalent groups with regard to patient history, indications for surgery, body mass index, length of surgery, and fluid requirements. Results: Core temperatures were significantly warmer during surgery (36.3°C ± 0.7°C vs 35.4 ± 0.8°C) and after surgery (36.4°C ± 0.7°C vs 35.6°C ± 0.9°C) in patients with forced air warming ( P < .001). The circulating water mattress group had significantly more metabolic acidosis perioperatively ( P = .03). Postoperative length of stay, cardiac complications, and death rates were not significantly different. Subgroup analysis of 83 aneurysm patients comparing normothermia with hypothermia (temperature less than 36°C) on arrival to the recovery room identified decreased cardiac output ( P = .02), thrombocytopenia ( P = .02), elevated prothrombin time ( P = .04), and inferior Acute Physiology and Chronic Health Evaluation (APACHE) II scores ( P < .001) in the hypothermic group. Holter analysis revealed more sinus tachycardia (ST) segment changes and ventricular tachycardia in hypothermic aneurysm patients ( P = .05). Conclusion: Patients treated with forced air blankets had significantly less metabolic acidosis and were kept significantly warmer than those treated with circulating water mattresses. Patients with aneurysms that were kept normothermic had a significantly improved clinical profile, with fewer cardiac events on the Holter recordings. We therefore conclude that (1) normothermia is protective for infrarenal aortic surgical patients; and (2) forced air warming blankets provide improved temperature maintenance compared with circulating water mattresses. (J Vasc Surg 1998;28:984-94.)

Evolution of Appropriate Technology

This paper considers the very significant challenges for Clinical Engineers when attempting to design medical technologies for use in lesser developed countries. The special problems concerning the care of ill newborn babies, and in particular, the impact of hypothermia and cold stress provided the focus for the work performed. A field study was carried out in both urban and rural settings of Iran as a developing country, the aims being to determine the incidence of hypothermia in the new-born, and to make observations concerning clinical and nursing procedures and equipment which may contribute to the problem. It was concluded that there is a need for training of both medical and technical staff, and there is also a requirement for a range of thermal control devices and procedures to help infants in different clinical circumstances. It was then decided to focus on the development of a simple, non-electric, safe, low cost and easily operated, heated transporting device which might increase the chances of survival of ill babies in rural and isolated areas being transferred to higher level clinical facilities in towns or cities. The laboratory design and preliminary laboratory testing of the device are described.

Hypothermia relieves oxidative stress in reperfused skeletal muscle following partial ischemia

The impact of hypothermia on reperfusion-associated oxidative stress in postischemic skeletal muscle was evaluated in a small animal model of high-grade partial ischemia. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and then reperfused for 60 min. Previous characterization of this model with 51Cr-tagged microspheres revealed that hindlimb perfusion during aortic clamping continued at 16.6% of baseline values. Resting transmembrane potential difference ( E m) and tissue malondialdehyde (MDA), lactate and high-energy phosphate content were determined in hindlimb skeletal muscle at baseline, during ischemia, and upon reperfusion. Four experimental groups ( N = 7 in each group) were studied: control animals underwent aortic clamping and declamping; hypothermia animals underwent topical cooling of hindlimbs prior to aortic clamping, with muscle temperatures maintained between 5 and 15°C during ischemia; sham animals underwent midline laparotomy only; and hypothermia-sham animals underwent cooling and midline laparotomy only. During ischemia, resting E m(−mV) was significantly depolarized ( P < 0.05 versus baseline) in control (74.9 ± 0.8 from 91.0 ± 0.1), hypothermia (64.4 ± 1.1 from 90.9 ± 0.3), and hypothermia-sham (67.2 ± 1.4 from 90.9 ± 0.4) animals. Upon reperfusion, resting E m remained depolarized in control animals (74.7 ± 1.6), while repolarization occurred in hypothermia (74.7 ± 1.6), while repolarization occurred in hypothermia (88.8 ± 1.1) and hypothermia-sham (90.7 ± 0.3) animals. Tissue MDA content (nmol/g wet tissue), a marker of phospholipid peroxidation, was markedly elevated ( P < 0.05 versus baseline) during ischemia in control (121.5 ± 18.4 from 67.1 ± 7.2) and hypothermia (118.5 ± 18.7 from 66.8 ± 7.5) animals, and continued to increase upon reperfusion in control animals (190.5 ± 14.0; P < 0.05 versus ischemia), while returning to baseline values in hypothermia animals (77.0 ± 12.8; P = NS versus baseline). These data indicate that high-grade partial ischemia in skeletal muscle is accompanied by significant phospholipid peroxidation, and that antecedent regional hypothermia markedly attenuates subsequent and further reperfusion-associated oxidative injury.