Rapid non-invasive external cooling to induce mild therapeutic hypothermia in adult human-sized swine

AIM OF THE STUDY: Mild therapeutic hypothermia is a promising new therapy for patients resuscitated from cardiac arrest. Early and fast induction of hypothermia seems to be crucial for best results. The aim of the study was to investigate the feasibility and safety of a new surface cooling method using cold metal plates. SUBJECTS AND METHODS: Twelve adult human-sized swine (79+/-9 kg) were cooled from 38 to 33 degrees C brain temperature. The skin surface was covered with -20 degrees C metal plates (M), as compared to ice packs, alcohol rubs, and fans used in a control group (C). Each method was tested during spontaneous circulation and, after re-warming, during cardiac arrest. Temperatures were recorded continuously. Data are given as mean+/-standard deviation or as median (interquartile range), if not normally distributed. Comparisons between the treatment groups were performed with the independent samples t-test, or the Mann-Whitney rank-sum test. RESULTS: During spontaneous circulation, cooling rates were 9.3+/-1.4 degrees C/h (M), and 6.1+/-1.4 degrees C/h (C) (p=0.003); no skin lesions were observed. During cardiac arrest, cooling rates were 4.1 degrees C/h (1.8-4.8) (M), and 3.7 degrees C/h (3.1-5.3) (C) (p=0.9); no skin lesions were observed. CONCLUSION: Cooling with cold metal plates was an effective method for rapid induction of mild therapeutic hypothermia in adult human-sized swine during spontaneous circulation, without any signs of skin damage. This new surface-cooling device, independent of energy supply during use, should be further investigated.     

Rapid induction of mild therapeutic hypothermia by extracorporeal veno-venous blood cooling in humans

Aim

Mild therapeutic hypothermia is beneficial in patients successfully resuscitated from non-traumatic out-of-hospital cardiac arrest. The effect of fast induction of hypothermia in these patients remains to be investigated. The aim of this study was to evaluate the efficacy and safety of extracorporeal veno-venous blood cooling in humans successfully resuscitated from cardiac arrest.

Methods

We performed an interventional study in patients after successful resuscitation from cardiac arrest admitted to the emergency department of a tertiary care centre. The extracorporeal veno-venous circulation was established via a percutaneously introduced double lumen dialysis catheter in the femoral vein, and a tubing circuit and heat exchanger. A paediatric cardiopulmonary bypass roller pump and a heater-cooler system were used to circulate the blood. Main outcome measures were feasibility, efficacy, and safety.

Results

We included eight consecutive cardiac arrest patients with a median oesophageal temperature of 35.9 °C (interquartile range 34.9–37.0). A median time of 8 min elapsed (interquartile range 5–15 min) to reach oesophageal temperatures below 34 °C, which reflects a cooling rate of 12.2 °C/h (interquartile range 10.8 °C/h to 14.1 °C/h). The predefined target temperature of 33.0 °C was reached after 14 min (interquartile range 8–21 min). No device or method related adverse events were reported.

Conclusion

Extracorporeal veno-venous blood cooling is a feasible, safe, and very fast approach for induction of mild therapeutic hypothermia in patients successfully resuscitated from cardiac arrest.     

Surface cooling for induction of mild hypothermia in conscious healthy volunteers - a feasibility trial

Introduction

Animal and human studies suggest beneficial outcome effects of mild hypothermia for stroke, for acute myocardial infarction, and for cardiogenic shock. The aim of this study was to investigate the feasibility and safety of non-invasive surface cooling for induction and maintenance of mild hypothermia (32 to 34°C) in healthy, conscious volunteers.

Methods

The trial was set at a clinical research ward in a tertiary care center, and included 16 healthy male volunteers 18 to 70 years old. Surface cooling was established by a novel non-invasive cooling pad with an esophageal target temperature of 32 to 34°C and maintenance for six hours. Shivering-control was achieved with meperidine and buspirone and additional administration of magnesium in eight subjects.

Results

The primary endpoint to reach a target temperature of 32 to 34°C was only reached in 6 of the 16 participating subjects. Temperatures below 35°C were reached after a median cooling time of 53 minutes (38 to 102 minutes). Cooling rate was 1.1°C/h (0.7 to 1.8°C). Additional administration of magnesium had no influence on cooling rate. At no time during the cooling procedure did the participants report uncomfortable conditions for which termination of cooling had to be considered. No severe skin damage was reported.

Conclusions

Cooling to body temperature below 35°C by the use of non-invasive surface cooling is feasible and safe in conscious healthy volunteers. Further studies are needed to investigate an altered cooling protocol to achieve temperatures below 35°C.

Trial Registration

ISRCTN: ISRCTN50530495     

Comparison of surface cooling and invasive cooling for rapid induction of mild therapeutic hypothermia in pigs--effectiveness of two different devices

Aim of the study

The effectiveness and safety of non-invasive surface cooling was compared to invasive endovascular cooling in an animal model.

Methods

Eight healthy pigs (29-38 kg) were cooled twice, starting in the first 4 pigs with unique surface cooling pads followed by endovascular cooling. In the second 4 pigs the order was reversed. The goal was to quickly lower pulmonary artery temperature from 38 to 33 °C. A paired t-test was used to compare cooling rates (°C/h, mean ± standard deviation) between both cooling techniques.

Results

Mean non-invasive surface cooling rate (11.9 ± 3.8 °C/h) significantly exceeded mean invasive cooling rate (3.9 ± 0.7 °C/h; p < 0.001). The mean difference in cooling rates was 8.0 ± 3.6 °C/h. No surface cooling related adverse skin reactions were observed.

Conclusions

Surface cooling is a simple method for achieving fast cooling rates. In our animal model, non-invasive cooling was three times faster than rapid endovascular cooling without overshoot.     

亚低温降温方法的研究进展

亚低温在临床的应用日益受到重视,应用范围在逐渐扩大,治疗手段日趋多样.近年来,亚低温被用于治疗新生儿缺氧性脑病、心肺复苏后脑保护、脑外伤及脑卒中等领域.目前临床应用较多的是冰袋降温法、医用冰毯降温法、选择性头部降温、全身亚低温疗法等.这些方法降温效果各有不同,存在不少缺点,部分方法还处于实验阶段.     

亚低温降温方法的研究进展

亚低温在临床的应用日益受到重视,应用范围在逐渐扩大,治疗手段日趋多样.近年来,亚低温被用于治疗新生儿缺氧性脑病、心肺复苏后脑保护、脑外伤及脑卒中等领域.目前临床应用较多的是冰袋降温法、医用冰毯降温法、选择性头部降温、全身亚低温疗法等.这些方法降温效果各有不同,存在不少缺点,部分方法还处于实验阶段.     

亚低温降温方式的研究现状

国际上按体温降低的程度将轻中度低温(28℃~35℃)统称为亚低温。亚低温在疾病预防和临床领域的应用日益广泛,显示出良好的应用前景。亚低温降温方式多样,降温装置也不断改善和发展。现将近年来亚低温降温方式综述如下。1冰袋降温法冰袋降温是临床上常用的方法。将冰袋用毛巾包裹置于枕后及全身大血管表浅处。但冰袋降温法致亚低温状态还存在一些问题:一是传统的清水冰袋形状固定,不易与体表充分接触;二是降温速度慢,体温降低速率是0.9℃/h,低温状态不恒定[1]。虽然许多临床护理工作者通过大量试验,对冰袋进行了改进,如使用盐水冰袋、化学冰…     

Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest--a feasibility study

OBJECTIVE: Mild therapeutic hypothermia has shown to improve neurological outcome after cardiac arrest. Our study investigated the efficacy and safety of cold simple intravenous infusions for induction of hypothermia after cardiac arrest preceding further cooling and maintenance of hypothermia by specialised endovascular cooling. METHODS: All patients admitted after cardiac arrest of presumed cardiac aetiology were screened. Patients enrolled received 2000 ml of ice-cold (4 degrees C) fluids via peripheral venous catheters. As soon as possible endovascular cooling was applied even if the cold infusions were not completed. The target temperature was defined as 33 +/- 1 degrees C. All temperatures recorded were measured via bladder-temperature probes. The primary endpoint was the time from return of spontaneous circulation to reaching the target temperature. Secondary endpoints were changes in haemodynamic variables, oxygenation, haemoglobin, clotting variables and neurological outcome. RESULTS: Out of 167 screened patients 26 (15%) were included. With a total amount of 24 +/- 7 ml/kg cold fluid at 4 degrees C the temperature could be lowered from 35.6 +/- 1.3 degrees C on admission to 33.8 +/- 1.1 degrees C. The target temperature was reached 185 +/- 119 min after return of spontaneous circulation, 135 +/- 112 min after start of infusion, and 83 +/- 85 min after start of endovascular cooling. Except for two patients showing radiographic signs of mild pulmonary edema no complications attributable to the infusions could be observed. Thirteen patients (50%) survived with favourable neurological outcome. CONCLUSION: Our results indicate that induction of mild hypothermia with infusion of cold fluids preceding endovascular cooling is safe and effective.     

The importance of surface area for the cooling efficacy of mild therapeutic hypothermia

Aim of the study

Mild hypothermia after cardiac arrest should be induced as soon as possible. There is a need for improved feasibility and efficacy of surface cooling in ambulances. We investigated which and how much area of the body surface should be covered to guarantee a sufficient cooling rate.

Methods

Each of five adult, human-sized pigs (88-105 kg) was randomly cooled in three phases with pads that covered different areas of the body surface corresponding to humans (100% or 30% [thorax and abdomen] or 7% [neck]). The goal was to quickly lower brain temperature (Tbr) from 38 to 33 °C within a maximum of 120 min. Linear regression analysis was used to test the association between cooling efficacy and surface area. Data are presented as mean ± standard deviation.

Results

The 100% and 30% cooling pads decreased the pigs’ Tbr from 38 to 33 °C within 33 ± 7 min (8.2 ± 1.6 °C/h) and 92 ± 24 min (3.6 ± 1.1 °C/h). The 7% achieved a final Tbr of 35.8 ± 0.7 °C after 120 min (1.1 ± 0.4 °C/h). The 30% and 7% cooling surface areas achieved 37 ± 11% and 15 ± 7% of the cooling rate compared to the 100% cooling pads. For every additional percent of surface area cooled, the cooling rate increased linearly by 0.07 °C/h (95% CI 0.05-0.09, p = 0.001). No skin lesions were observed.

Conclusions

The cooling pads were effective and safe for rapid induction of mild hypothermia in adult, human-sized pigs, depending on the percentage of body surface area covered. Covering only the neck, chest, and abdomen might achieve satisfactory cooling rates.     

亚低温对猪脓毒性休克时心肌的影响

目的 探讨亚低温对猪脓毒性休克时心肌的保护作用.方法 24头贵州小型猪随机(随机数字法)分为休克前亚低温组、休克后亚低温组和常温对照组,每组8头.麻醉后股静脉注入大肠杆菌内毒素制作猪脓毒症模型.制模后各组同时用输液泵以相同速度股静脉持续输入生理盐水,休克前亚低温组用4℃的生理盐水,常温对照组和休克后亚低温组用38℃的生理盐水,休克后亚低温组在动脉收缩压降至基础值的60%,维持1 h后,开始改用4℃的生理盐水.制模前和制模后温度干预6 h、12h时观察各组心脏血流动力学指标、血乳酸、肌钙蛋白I(CTnI)、冠状动脉造影TIMI血流、电镜下心肌超微结构变化.结果 6 h,12 h后,休克前亚低温组各项指标均显著优于休克后亚低温组和常温对照组(P<0.01).6 h后,休克后亚低温组的CTnI、超微结构损伤变化轻于常温对照组(P<0.05),但两组血乳酸、TIMI血流、血流动力学指标变化差异无统计学意义(P>0.05).12 h后,休克后亚低温组各项指标和常温对照组差异无统计学意义(P>0.05).结论 亚低温对猪脓毒症时的心肌有一定的保护作用;猪脓毒性休克发生以前早期使用亚低温对心肌的保护作用和改善心功能较明显;猪脓毒性休克发生以后,亚低温可以延缓心肌损伤的速度,但并不减轻心肌损伤的程度,也不能减少心功能的丧失.     

Veno-venous extracorporeal blood shunt cooling to induce mild hypothermia in dog experiments and review of cooling methods

Mild hypothermia (33-36 degrees C) might be beneficial when induced during or after insults to the brain (cardiac arrest, brain trauma, stroke), spinal cord (trauma), heart (acute myocardial infarction), or viscera (hemorrhagic shock). Reaching the target temperature rapidly in patients inside and outside hospitals remains a challenge. This study was to test the feasibility of veno-venous extracorporeal blood cooling for the rapid induction of mild hypothermia in dogs, using a simple pumping-cooling device. Ten custom-bred hunting dogs (21-28 kg) were lightly anesthetized and mechanically ventilated. In five dogs, two catheters were inserted through femoral veins, one peripheral and the other into the inferior vena cava. The catheters were connected via a coiled plastic tube as heat exchanger (15 m long, 3 mm inside diameter, 120 ml priming volume), which was immersed in an ice-water bath. A small roller-pump produced a veno-venous flow of 200 ml/min (about 10% of cardiac output). In five additional dogs (control group), a clinically practiced external cooling method was employed, using alcohol over the skin of the trunk and fanning plus ice-bags. During spontaneous normotension, veno-venous cooling delivered blood into the vena cava at 6.2 degrees C standard deviation (SD 1.4) and decreased tympanic membrane (Tty) temperature from 37.5 to 34.0 degrees C at 5.2 min (SD 0.7), and to 32.0 degrees C at 7.9 min (SD 1.3). Skin surface cooling decreased tympanic temperature from 37.5 to 34.0 degrees C at 19.9 min (SD 3.7), and to 32.0 degrees C at 29.9 (SD 5.1) (P=0.001). Heart rates at Tty 34 and 32 degrees C were significantly lower than at baseline in both groups, but within physiological range, without difference between groups. There were no arrhythmias. We conclude that in large dogs the induction of mild systemic hypothermia with extracorporeal veno-venous blood shunt cooling is simple and four times more rapid than skin surface cooling.     

Intraosseous infusion of ice cold saline is less efficacious than intravenous infusion for induction of mild therapeutic hypothermia in a swine model of cardiac arrest

Background

Intravenous (IV) infusion of ice cold saline is an effective method to initiate induction of mild therapeutic hypothermia (MTH) following resuscitation from out-of-hospital cardiac arrest (OOHCA). Intraosseous (IO) infusion of cold saline may be an alternative method to induce MTH.

Objective

The goal of this study was to determine if IO infusion of cold saline is a comparable alternative to IV infusion for inducing MTH in a laboratory swine model of cardiac arrest.

Methods

Ten mixed breed swine were resuscitated from cardiac arrest and randomized post-resuscitation to infusion with ice cold saline using either IO (n = 5) or IV (n = 5) access. The study endpoints were either a goal esophageal temperature of 34 °C or the elapse of a 30 min time period, simulating a long prehospital transport.

Results

Four of five pigs in the IV infusion group achieved goal temperature within 30 min compared to 0/5 in the IO infusion group (p = 0.048). The mean esophageal temperature change was significantly higher in the IV group when compared to the IO group (p < 0.001). Post-arrest hemodynamic parameters were similar between the two groups.

Conclusions

IV infusion of ice cold saline is an efficacious method to achieve MTH in this swine model of cardiac arrest. Furthermore, IO infusion of cold saline is not sufficient to induce MTH in the time routinely available in the prehospital setting following OOHCA.     

Feasibility of intra-arrest hypothermia induction: A novel nasopharyngeal approach achieves preferential brain cooling

Aim

In patients with cardiopulmonary arrest, brain cooling may improve neurological outcome, especially if applied prior to or during early reperfusion. Thus it is important to develop feasible cooling methods for pre-hospital use. This study examines cerebral and compartmental thermokinetic properties of nasopharyngeal cooling during various blood flow states.

Methods

Ten swine (40 ± 4 kg) were anesthetized, intubated and monitored. Temperature was determined in the frontal lobe of the brain, in the aorta, and in the rectum. After the preparatory phase the cooling device (RhinoChill™ system), which produces evaporative cooling in the nasopharyngeal area, was activated for 60 min. The thermokinetic response was evaluated during stable anaesthesia (NF, n = 3); during untreated cardiopulmonary arrest (ZF, n = 3); during CPR (LF, n = 4).

Results

Effective brain cooling was achieved in all groups with a median cerebral temperature decrease of −4.7 °C for NF, −4.3 °C for ZF and −3.4 °C for LF after 60 min. The initial brain cooling rate however was fastest in NF, followed by LF, and was slowest in ZF; the median brain temperature decrease from baseline after 15 min of cooling was −2.48 °C for NF, −0.12 °C for ZF, and −0.93 °C for LF, respectively. A median aortic temperature change of −2.76 °C for NF, −0.97 for LF and +1.1 °C for ZF after 60 min indicated preferential brain cooling in all groups.

Conclusion

While nasopharyngeal cooling in swine is effective at producing preferential cerebral hypothermia in various blood flow states, initial brain cooling is most efficient with normal circulation.     

Fast hypothermia induced by extracorporeal circuit cooling alleviates renal and intestinal injury after cardiac arrest in swine

BackgroundContinuous renal replacement therapy (CRRT) was currently demonstrated to be an effective way to induce fast hypothermia and had proective effects on cardiac dysfunction and brain damage after cardiac pulmonary resuscitation (CPR). In the present study, we aimed to investigate the influence of extracorporeal circuit cooling using CRRT on renal and intestinal damage after CPR based on a porcine model.Methods32 pigs were subjected to ventricular fibrillation for 8 min, followed by CPR for 5 min before defibrillation. All were randomized to receive extracorporeal circuit cooling using CRRT (CRRT, n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (n = 5) at 5 min post resuscitation. Pigs in the CRRT group were cooled by 8-h CRRT cooling with the infusion line initially submerged in 4 °C of ice water and 16-h SC, while in the SC group by a 24-h SC. Temperatures were maintained at a normal range in the other two groups. Biomarkers in serum were measured at baseline and 1, 3, 6, 12, 24 and 30 h post resuscitation to assess organ functions. Additionally, tissues of kidney and intestine were harvested, from which the degree of tissue inflammation, oxidative stress, and apoptosis levels were analyzed.ResultsThe blood temperature decreased faster by extracorporeal circuit cooling using CRRT than SC (9.8 ± 1.6 vs. 1.5 ± 0.4 °C/h, P < 0.01). Post-resuscitation renal and intestinal injury were significantly improved in the 2 hypothermic groups compared to the NT group. And the improvement was significantly greater in animals received extracorporeal circuit cooling than those received surface cooling, from both the results of biomarkers in serum and pathological evidence.ConclusionFast hypothermia induced by extracorporeal circuit cooling was superior to.surface cooling in mitigating renal and intestinal injury post resuscitation.     

A rapid, safe, and low-cost technique for the induction of mild therapeutic hypothermia in post-cardiac arrest patients

Aim of study

The benefits of inducing mild therapeutic hypothermia (MTH) in cardiac arrest patients are well established. Timing and speed of induction have been related to improved outcomes in several animal trials and one human study. We report the results of an easily implemented, rapid, safe, and low-cost protocol for the induction of MTH.

Methods

All in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA) patients admitted to an intensive care unit meeting inclusion criteria were cooled using a combination modality of rapid, cold saline infusion (CSI), evaporative surface cooling, and ice water gastric lavage. Cooling tasks were performed with a primary emphasis on speed. The main endpoints were the time intervals between return of spontaneous circulation (ROSC), initiation of hypothermia (IH), and achievement of target temperature (TT).

Results

65 patients underwent MTH during a 3-year period. All patients reached target temperature. Median ROSC-TT was 134 min. Median ROSC-IH was 68 min. Median IH-TT was 60 min. IH-TT cooling rate was 2.6 °C/h. Complications were similar to that of other large trials. 31% of this mixed population of IHCA and OHCA patients recovered to a Pittsburgh cerebral performance score (CPC) of 1 or 2.

Conclusion

A protocol using a combination of core and surface cooling modalities was rapid, safe, and low cost in achieving MTH. The cooling rate of 2.6 °C/h was superior to most published protocols. This method uses readily available equipment and reduces the need for costly commercial devices.     

Normal saline versus colloid solutions for induction of hypothermia: the effect of specific heat capacity on cooling

The prevention of ischemic injury to preserve both end-organ function and improve neurological recovery by the implementation of therapeutic hypothermia has been well established in the literature. However, not only the means by which body temperature is cooled but also the rate by which target temperature is attained remains an area of continued interest and research. The induction of therapeutic hypothermia to begin the process of body temperature lowering through the infusion of a cold solution intravenously into the body may be one variable that influences not only rapidity of cooling but also subsequent clinical outcome. In a recent issue of Critical Care, Skulec and colleagues compared the induction of therapeutic hypothermia by cold normal saline versus cold colloid solution containing hydroxyethyl starch in a porcine animal model of cardiac arrest, assessing both the rate of temperature change and target temperature achieved, in addition to changes in intracranial pressure.The use of therapeutic hypothermia (TH) in clinical medicine is no longer a rarity. A variety of methods have been implemented in an attempt to cool patients faster [1]. In a recent issue of Critical Care, Skulec and colleagues [2] evaluated the efficacy of cold normal saline as compared with a colloid solution containing hydroxyethyl starch in the induction of TH in survivors of cardiac arrest by using a porcine animal model of ventricular fibrillation (VF). A 20-minute infusion of either 45 mg/mL of 1°C cold normal saline or 45 mg/mL of 1°C cold colloid solution (Voluven, 6% hydroxyethyl starch 130/0.4 in normal saline; Fresenius Kabi AG, Bad Homburg, Germany) was administered following 5 minutes of VF and subsequent resuscitation. Comparison of pulmonary blood temperature and cerebral blood temperature demonstrated a statistically significant decrease in temperature in animals given normal saline (-2.1 ± 0.3 versus -1.6 ± 0.2°C, and -1.7 ± 0.4 versus -1.1 ± 0.3°C, P <0.05, respectively). Moreover, initiation of TH with normal saline resulted in accelerated cooling when compared with colloid solution (-91 ± 22 versus -68 ± 23°C/min, P = 0.046). The authors also performed a mechanical substudy evaluating the specific heat capacities of each fluid and demonstrated that normal saline resulted in statistically more significant cooling than the studied colloid solution (-7,155 ± 647 versus -5,733 ± 636°C/min, P = 0.008), and this is consistent with the above clinical in vivo findings.These results demonstrating the differential cooling of normal saline compared with a colloid solution containing hydroxyethyl starch both in vivo and experimentally by Skulec and colleagues are both novel academically and consistent with the understanding of specific heat capacity of solutions following the addition of solutes from thermodynamics. Briefly, the addition of a solute to a solution results in an increase in the number of particles that can absorb energy and release it as heat, in turn resulting in an increase in the temperature of the solute-solution combination relative to the solution alone when a constant amount of energy is applied [3]. As the authors demonstrated, the thermodynamic effect of adding solute to a solution resulted in statistically significant differences clinically with respect to hypothermia induction and temperatures attained, as well as rapidity of cooling [2].Interestingly, the intracranial pressure (ICP) was increased in animals treated with cold colloid solution containing hydroxyethyl starch as compared with normal saline solution (end infusion ICPs of 25 ± 5 and 16 ± 6 mm Hg, respectively), which persisted for up to 90 minutes following infusion. The association of increased ICP with hydroxyethyl starch was also demonstrated by Khan and colleagues, who evaluated the combined incidence of delayed cerebral ischemia, hydrocephalous requiring cerebrospinal fluid shunting, and rebleeding in patients following subarachnoid hemorrhage, and demonstrated a statistically significant increase in both the combined endpoint (odds ratio 3.1, 95% confidence interval 1.30 to 7.36, P = 0.01) and the incidence of hydrocephalous requiring cerebrospinal fluid shunting (odds ratio 6.1, 95% confidence interval 1.63 to 22.95, P = 0.004) [4]. The increases in both ICP and hydrocephalous requiring cerebrospinal fluid shunting in these two studies are most likely due to changes in cerebrospinal fluid absorption by the arachnoid microvilli related to hydroxyethyl starch.The use of colloid solutions containing hydroxyethyl starch for volume resuscitation of critically ill patients has been controversial, and the literature suggests both increased mortality and increased need for renal replacement therapy when compared with normal saline, and subsequently the US Food and Drug Administration issued a boxed recommendation to health-care professionals not to use hydroxyethyl starch-containing solutions in patients admitted to the intensive care unit or in patients with pre-existing renal dysfunction [5-7]. The ICP increase seen by Skulec and colleagues in animals treated with colloid solution may be, in part, the mechanism associated with increased mortality in patients treated with hydroxyethyl starch solutions. This study not only elucidates the decreased efficacy of colloid solutions containing hydroxyethyl starch compared with normal saline in the induction of TH in vivo but also provides insight into complications associated with hydroxyethyl starch and re-emphasizes the importance of specific heat capacity of the solution with respect to rapidity of cooling during TH induction.