Role of perfusion medium in rewarming machine perfusion from hypo- to normothermia.

BACKGROUND: Gradual warming up of cold stored organ grafts using a controlled machine perfusion protocol facilitates restitution of cellular homeostasis and mitigates rewarming injury by adapted increase of temperature and metabolism. The aim of the present study was to compare intra- and extracellular type perfusion media for the use in machine perfusion-assisted rewarming from hypo- to normothermia. METHODS: Rat livers were retrieved 20 min after cardiac arrest. After 18 h of cold storage (CS) with or without additional 2 h of rewarming machine perfusion from 8°C up to 35°C with either diluted Steen solution or with Belzer MPS, liver functional parameters were evaluated by an established ex vivo reperfusion system. RESULTS: Rewarming machine perfusion with either solution significantly improved graft performance upon reperfusion in terms of increased bile production, less enzyme release, and reduced lipid peroxidation compared to CS alone. Cellular apoptosis (release of caspase-cleaved keratin 18) and release of tumor necrosis factor were only reduced significantly after machine perfusion with Belzer MPS. Histological evaluation did not disclose any major morphological damage in any of the groups. CONCLUSION: Within the limitation of our model, the use of Belzer MPS seems to be an at least adequate alternative to a normothermic medium like Steen solution for rewarming machine perfusion of cold liver grafts.

ß-adrenergic stimulation after rewarming does not mitigate hypothermia-induced contractile dysfunction in rat cardiomyocytes.

Victims of severe accidental hypothermia are frequently treated with catecholamines to counteract the hemodynamic instability associated with hypothermia-induced cardiac contractile dysfunction. However, we previously reported that the inotropic effects of epinephrine are diminished after hypothermia and rewarming (H/R) in an intact animal model. Thus, the goal of this study was to investigate the effects of Epi treatment on excitation-contraction coupling in isolated rat cardiomyocytes after H/R. In adult male rats, cardiomyocytes isolated from the left ventricle were electrically stimulated at 0.5 Hz and evoked cytosolic [Ca2+] and contractile responses (sarcomere length shortening) were measured. In initial experiments, the effects of varying concentrations of epinephrine on evoked cytosolic [Ca2+] and contractile responses at 37 °C were measured. In a second series of experiments, cardiomyocytes were cooled from 37 °C to 15 °C, maintained at 15 °C for 2 h, then rewarmed to 37 °C (H/R protocol). Immediately after rewarming, the effects of epinephrine treatment on evoked cytosolic [Ca2+] and contractile responses of cardiomyocytes were determined. At 37 °C, epinephrine treatment increased both cytosolic [Ca2+] and contractile responses of cardiomyocytes in a concentration-dependent manner peaking at 25-50 nM. The evoked contractile response of cardiomyocytes after H/R was reduced while the cytosolic [Ca2+] response was slightly elevated. The diminished contractile response of cardiomyocytes after H/R was not mitigated by epinephrine (25 nM) and epinephrine treatment reduced the exponential time decay constant (Tau), but did not increase the cytosolic [Ca2+] response. We conclude that epinephrine treatment does not mitigate H/R-induced contractile dysfunction in cardiomyocytes.

Effects of rewarming therapies on outcomes in accidental hypothermia: A secondary analysis of a multicenter prospective study.

BACKGROUND: Rewarming therapies for accidental hypothermia (AH) include extracorporeal membrane oxygenation (ECMO) and non-ECMO related (conventional) therapies. However, there are limited data available to inform the selection of conventional rewarming therapy. The aim of the present study was to explore what patients' factors and which rewarming therapy predicted favorable prognosis. METHODS: This study is a secondary analysis of the Intensive Care with Extra Corporeal membrane oxygenation Rewarming in Accidentally Severe Hypothermia (ICE-CRASH) study, a multicenter prospective, observational study conducted in Japan. Enrolled in the ICE-CRASH study were patients aged ≥18 years with a core temperature of ≤32 °C who were transported to the emergency departments of 36 tertiary care hospitals in Japan between 1 December 2019 and 31 March 2022, among whom those who were rewarmed with conventional rewarming therapy were included in the present study. Logistic regression analysis was performed with 28-day survival as the objective variable; and seven factors including age, activities of daily living (ADL) independence, sequential organ failure assessment (SOFA) score, and each rewarming technique as explanatory variables. We performed linear regression analysis to identify whether each rewarming technique was associated with rewarming rate. RESULTS: Of the 499 patients enrolled in the ICE-CRASH study, 371 were eligible for this secondary analysis. The median age was 81 years, 50.9% were male, and the median initial body temperature was 28.8 °C. Age (odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.94-1.00) and SOFA score (OR: 0.73, 95% CI: 0.67-0.81) were associated with lower survival, whereas ADL independence (OR: 2.31, 95% CI: 1.15-4.63) was associated with higher survival. No conventional rewarming therapy was associated with 28-day survival. Hot bath was associated with a high rewarming rate (regression coefficient: 1.14, 95% CI: 0.75-1.53). CONCLUSION: No conventional rewarming therapy was associated with improved 28-day survival, which suggests that background factors such as age, ADL, and severity of condition contribute more to prognosis than does the selection of rewarming technique.

Predictors of cardiac arrest in severe accidental hypothermia.

STUDY OBJECTIVE: To indicate predictors of witnessed hypothermic cardiac arrest. METHODS: We conducted a retrospective analysis of 182 patients with severe accidental hypothermia (i.e., with core body temperature of ≤28 °C) who presented with preserved spontaneous circulation at first contact with medical services. We divided the study population into two groups: patients who suffered hypothermic cardiac arrest (HCA) at any time between encounter with medical service and restoration of normothermia, and those who did not sustain HCA. The analyzed outcome was the occurrence of cardiac arrest prior to achieving normothermia. Hemodynamic and biochemical parameters were analyzed with regard to their association with the outcome. RESULTS: Fifty-two (29%) patients suffered HCA. In a univariable analysis, four variables were significantly associated with the outcome, namely heart rate (p < 0.001), systolic blood pressure (p = 0.03), ventricular arrhythmia (p = 0.001), and arterial oxygen partial pressure (p = 0.002). In the multivariable logistic regression the best model predicting HCA included heart rate, PaO2, and Base Excess (AUROC = 0.78). In prehospital settings, when blood gas analysis is not available, other multivariable model including heart rate and occurrence of ventricular arrhythmia (AUROC = 0.74) can be used. In this study population, threshold values of heart rate of 43/min, temperature-corrected PaO2 of 72 mmHg, and uncorrected PaO2 of 109 mmHg, presented satisfactory sensitivity and specificity for HCA prediction. CONCLUSIONS: In patients with severe accidental hypothermia, the occurrence of HCA is associated with a lower heart rate, hypoxemia, ventricular arrhythmia, lower BE, and lower blood pressure. These parameters can be helpful in the early selection of high-risk patients and their allocation to extracorporeal rewarming facilities.

Cold-induced vasodilation during sequential immersions of the hand.

A common practice for those operating in cold environments includes repetitive glove doffing and donning to perform specific tasks, which creates a repetitive cycle of hand cooling and rewarming. This study aimed to determine the influence of intraday repeated hand cooling on cold-induced vasodilation (CIVD), sympathetic activation, and finger/hand temperature recovery. Eight males and two females (mean ± SD age: 28 ± 5 year; height: 181 ± 9 cm; weight: 79.9 ± 10.4 kg) performed two 30-min hand immersions in cold (4.3 ± 0.92 °C) water in an indoor environment (18 °C). Both immersions (Imm1; Imm2) were performed on the same day and both allowed for a 10-min recovery. CIVD components were calculated for each finger (index, middle, ring) during each immersion. CIVD onset time (index, p = 0.546; middle, p = 0.727; ring, p = 0.873), minimum finger temperature (index, p = 0.634; middle, p = 0.493; ring, p = 0.575), and mean finger temperature (index, p = 0.986; middle, p = 0.953; ring, p = 0.637) were all similar between immersions. Recovery rates generally demonstrated similar responses as well. Findings suggest that two sequential CIVD tests analyzing the effect of prior cold exposure of the hand does not impair the CIVD response or recovery. Such findings appear promising for those venturing into cold environments where hands are likely to be repeatedly exposed to cold temperatures.

Effect of wet clothing removal on skin temperature in subjects exposed to cold and wrapped in a vapor barrier: a human, randomized, crossover field study.

BACKGROUND: Prehospital care for cold-stressed and hypothermic patients focuses on effective insulation and rewarming. When encountering patients wearing wet clothing, rescuers can either remove the wet clothing before isolating the patient or isolate the patient using a vapor barrier. Wet clothing removal increases skin exposure but avoids the need to heat the wet clothing during rewarming. Leaving wet clothing on will avoid skin exposure but is likely to increase heat loss during rewarming. This study aimed to evaluate the effect of wet clothing removal compared to containing the moisture using a vapor barrier on skin temperature in a prehospital setting. METHODS: This randomized crossover experimental field study was conducted in a snow cave in Hemsedal, Norway. After an initial cooling phase of 30 min while wearing wet clothes, the participants were subjected to one of two rewarming scenarios: (1) wet clothing removal and wrapping in a vapor barrier, insulating blankets, and windproof outer shell (dry group) or (2) wrapping in a vapor barrier, insulating blankets, and windproof outer shell (wet group). The mean skin temperature was the primary outcome whereas subjective scores for both thermal comfort and degree of shivering were secondary outcomes. Primary outcome data were analyzed using the analysis of covariance (ANCOVA). RESULTS: After an initial decrease in temperature during the exposure phase, the dry group had a higher mean skin temperature compared to the wet group after only 2 min. The skin-rewarming rate was highest in the initial rewarming stages for both groups, but increased in the dry group as compared to the wet group in the first 10 min. Return to baseline temperature occurred significantly faster in the dry group (mean 12.5 min [dry] vs. 28.1 min [wet]). No intergroup differences in the subjective thermal comfort or shivering were observed. CONCLUSION: Removal of wet clothing in combination with a vapor barrier increases skin rewarming rate compared to encasing the wet clothing in a vapor barrier, in mild cold and environments without wind. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05996757, retrospectively registered 18/08/2023.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2024 Update.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2019.

Surviving 20 Hours of Critical Avalanche Burial and a Core Temperature of 22.5 °C.

A 24-year-old male snowboarder was buried in an avalanche for 20 h and rescued on the next day at a depth of 2.3 m below the snow surface. A large air pocket was noted in front of his mouth and nose. He was responsive but moved restlessly and uncoordinatedly. The epitympanic temperature was 22.5 °C. He was bradycardic (35/min), and a right bundle branch block with Osborn waves was noted. Rewarming (1 °C/h) was initiated with continuous hemodialysis; core temperature raised to 29.8 °C within 4 h. At 30 °C he became conscious. With rewarming, the heart rate increased to 90 beats per minute and the ECG changes disappeared; nonfreezing cold injuries were noted. On the next day, his pulmonary function deteriorated-fluid overload of 9 L since admission was diagnosed. With spontaneous diuresis, the situation improved. On Day 4, the neurologist reported subtle polyneuropathy in both legs secondary to hypothermia, without tendency to regress. This case occurred more than 20 years ago but has not been reported yet. To this day, this is the third-longest critical avalanche burial ever reported. We discuss the circumstances of this accident, the clinical course, and how treatment has changed since 2000.

The Effect of Warmed Serum on Shivering and Recovery Period of Patients Under General and Spinal Anesthesia: A Randomized Clinical Trial.

PURPOSE: Postoperative hypothermia followed by shivering is a common phenomenon in patients undergoing surgery under anesthesia, and should be prevented and treated in postoperative patient care units. This study was conducted to investigate the effect of warmed serum injection on postoperative shivering and recovery period of patients operated under general and spinal anesthesia. DESIGN: In this clinical trial, patients to be operated on under general and spinal anesthesia were randomly assigned into two groups of test and control. In the test group, patients received warmed intravenous fluids and blood products. All patients were monitored to record vital signs, incidences of hypothermia and shivering, and recovery period. METHODS: The collected data were analyzed with repeated measures analysis of variance to detect significant differences between groups and significant changes within groups over time. FINDINGS: The incidence of nausea, vomiting, and shivering in the intervention and control groups was (4.7%, 42%), (2.8%, 16.8%), and (6.6%, 43%), respectively. Patients in the intervention group had higher body temperature than the control group (<0.001). Also, patients under spinal anesthesia had higher body temperature than patients under general anesthesia (<0.001). Blood pressure reduction was also significantly higher in the control group than in the intervention group. The patients who received warm intravenous serum, and especially those who had received spinal anesthesia spent less time in the recovery room (<0.001). CONCLUSIONS: The use of warmed intravenous serum increased the patients' core temperature, reduced their postoperative shivering, and shortened their recovery period. Considering the potential risks associated with hypothermia, using such methods for hypothermia prevention can be highly effective in preventing shivering and prolongation of the recovery period and other potential complications. Anesthesia specialists and technicians are therefore encouraged to use this method as a preventive measure.

Physiological Impact of Hypothermia: The Good, the Bad, and the Ugly.

Hypothermia is defined as a core body temperature of <35°C, and as body temperature is reduced the impact on physiological processes can be beneficial or detrimental. The beneficial effect of hypothermia enables circulation of cooled experimental animals to be interrupted for 1-2 h without creating harmful effects, while tolerance of circulation arrest in normothermia is between 4 and 5 min. This striking difference has attracted so many investigators, experimental as well as clinical, to this field, and this discovery was fundamental for introducing therapeutic hypothermia in modern clinical medicine in the 1950s. Together with the introduction of cardiopulmonary bypass, therapeutic hypothermia has been the cornerstone in the development of modern cardiac surgery. Therapeutic hypothermia also has an undisputed role as a protective agent in organ transplantation and as a therapeutic adjuvant for cerebral protection in neonatal encephalopathy. However, the introduction of therapeutic hypothermia for organ protection during neurosurgical procedures or as a scavenger after brain and spinal trauma has been less successful. In general, the best neuroprotection seems to be obtained by avoiding hyperthermia in injured patients. Accidental hypothermia occurs when endogenous temperature control mechanisms are incapable of maintaining core body temperature within physiologic limits and core temperature becomes dependent on ambient temperature. During hypothermia spontaneous circulation is considerably reduced and with deep and/or prolonged cooling, circulatory failure may occur, which may limit safe survival of the cooled patient. Challenges that limit safe rewarming of accidental hypothermia patients include cardiac arrhythmias, uncontrolled bleeding, and "rewarming shock."

Microcirculatory effects of rewarming in experimental hemorrhagic shock.

BACKGROUND: Rewarming is a recommended therapy during the resuscitation of hypothermic patients with hemorrhagic shock. In experimental models, however, it increases inflammatory response and mortality. Although microcirculation is potential target of inflammation, the microvascular effects of rewarming during the resuscitation of hemorrhagic shock have not been studied. Our goal was to assess the systemic and microcirculatory effects of an increase in core temperature (T°) during the retransfusion of hemorrhagic shock in sheep. Our hypothesis was that rewarming could hamper microcirculation. METHODS: In anesthetized and mechanically ventilated sheep, we measured systemic, intestinal, and renal hemodynamics and oxygen transport. O2 consumption (VO2) and respiratory quotient were measured by indirect calorimetry. Cortical renal, intestinal villi and sublingual microcirculation were assessed by IDF-videomicroscopy. After basal measurements, hemorrhagic shock was induced and T° was reduced to ~33 °C. After 1 h of shock and hypothermia, blood was retransfused and Ringer lactate solution was administered to prevent arterial hypotension. In the control group (n = 12), T° was not modified, while in the intervention (rewarming) group, it was elevated ~3 °C. Measurements were repeated after 1 h. RESULTS: During shock, both groups showed similar systemic and microvascular derangements. After retransfusion, VO2 remained decreased compared to baseline in both groups, but was lower in the control compared to the rewarming group. Perfused vascular density has a similar behavior in both groups. Compared to baseline, it remained reduced in peritubular (control vs. rewarming group, 13.8 [8.7-17.5] vs. 15.7 [10.1-17.9] mm/mm2, PNS) and villi capillaries (14.7 [13.6-16.8] vs. 16.3 [14.2-16.9] mm/mm2, PNS), and normalized in sublingual mucosa (19.1 [16.0-20.3] vs. 16.6 [14.7-17.2] mm/mm2, PNS). CONCLUSIONS: This is the first experimental study assessing the effect of rewarming on systemic, regional, and microcirculatory perfusion in hypothermic hemorrhagic shock. We found that a 3 °C increase in T° neither improved nor impaired the microvascular alterations that persisted after retransfusion. In addition, sublingual mucosa was less susceptible to reperfusion injury than villi and renal microcirculation.

Influence of acute beetroot juice supplementation on cold-induced vasodilation and fingertip rewarming.

PURPOSE: Vasoactive ingredients in beetroot (BR) such as nitrate are known to induce vasodilation in temperate conditions. This study investigated the effect of BR ingestion on cold induced vasodilation (CIVD) and rewarming of finger skin temperature (Tfing) during and after hand immersion in cold water. METHODS: Twenty healthy males (mean ± SD; age 22.2 ± 0.7 years, height 172.6 ± 6.0 cm, body mass 61.3 ± 11.7 kg) repeated a hand cold water immersion test twice with prior BR or water beverage ingestion (randomised order). They rested for 2 h in thermoneutral conditions (27 °C, 40% relative humidity) after consuming the beverage, then immersed their non-dominant hand in 8 °C water for 30 min. They then rewarmed their hand in the ambient air for 20 min. Skin temperature at seven body sites, Tfing, finger skin blood flow (SkBFfing), and blood pressure were measured. RESULTS: During hand immersion parameters of CIVD (Tfing and SkBFfing) were not different between BR and water conditions although skin temperature gradient from proximal to distal body sites was significantly smaller with BR (P < 0.05). During rewarming, SkBFfing and cutaneous vascular conductance were significantly higher with BR than with water (P < 0.05). The rewarming speed in Tfing and SkBFfing was significantly faster with BR at 15- (BR 1.24 ± 0.22 vs water 1.11 ± 0.26 °C/min) and 20-min rewarming (P < 0.05). Additionally, individuals with slower rewarming speed with water demonstrated accelerated rewarming with BR supplementation. CONCLUSION: BR accelerated rewarming in Tfing and SkBFfing after local cold stimulus, whereas, CIVD response during hand cold immersion was not affected by BR ingestion.

Cerebral oxygenation and autoregulation during rewarming on cardiopulmonary bypass.

BACKGROUND: Rewarming on cardiopulmonary bypass (CPB) is associated with increased metabolic demands; however, it remains unclear whether cerebral autoregulation is affected during this phase. This RCT aims to describe the effects of 20% supranormal, compared to normal CPB flow, on monitoring signs of inadequate perfusion, oxygenation, and disturbed cerebral autoregulation, during the rewarming phase of CPB. METHOD: Thirty two patients scheduled for coronary artery bypass grafting were allocated to a Control group (n = 16) receiving a CPB pump flow corresponding to preoperatively measured cardiac output, and an Intervention group (n = 16) receiving the corresponding CPB pump flow increased by 20% during rewarming. Cerebral Oximetry Index (COx) was calculated with the aid of Near Infrared Spectroscopy. RESULTS: Twenty five patients were included in the data. Results show a median COx value of 0.0 (IQR -0.33-0.5) (Control) and 0.0 (IQR -0.15-0.25) (Intervention), respectively; p = .85 with individual variations within groups. The median cerebral perfusion pressure (CPP) was 55 (52-58) (Control) and 61 (54-66) mmHg (Intervention); p = .08. No significant difference in rSO2 values was observed between the groups (58.5% (50-61) versus 64% (58-68); p = .06). CONCLUSION: The present study showed no difference between increased and normal CPB pump flow with respect to cerebral autoregulation during rewarming. Large variations in cerebral autoregulation were seen at individual level.

Hypothermic rescue by veno-arterial extracorporeal membrane oxygenation: A case report.

INTRODUCTION: Severe hypothermia is a life-threatening condition that often causes hemodynamic instability or cardiac arrest and carries a high risk of mortality. The use of VA-ECMO in this indication has greatly improved the prognosis of patients. CASE REPORT: We describe an incredible case involving the complete recovery of a 47-year-old man placed on VA-ECMO for cardiogenic shock and protracted ventricular fibrillation caused by hypothermia. The patient was discharged home in 20 days with no neurologic sequelae. CLINICAL DISCUSSION: Extracorporeal life support (ECLS) with cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) has been recommended as the gold standard for the treatment of severe hypothermia due to its rapid availability and the possibility of prolonged support. Our case demonstrates the effectiveness of ECMO in treating patients with hypothermic cardiogenic shock. At the same time, nutritional support and rehabilitation therapy play an integral role in the whole treatment process. Therefore, it is recommended that such patients be managed by an experienced cardiac team that can evaluate the patient's condition in multiple aspects. CONCLUSION: ECMO may be an effective treatment for hypothermia-induced cardiogenic shock, but further research is needed on the effectiveness of this method of treatment.

Rewarming from unwitnessed hypothermic cardiac arrest with good neurological recovery using extracorporeal membrane oxygenation.

A 26-year-old man, who was training in bad weather for a mountain ultramarathon, became hypothermic after running for 4 h. He deteriorated and was unable to continue. His running partner went for help. The man suffered an unwitnessed hypothermic cardiac arrest. The on-site management and evacuation are described and included the use of intermittent cardiopulmonary resuscitation and a mechanical device during transport. The patient was successfully resuscitated and rewarmed by Extracorporeal Membrane Oxygenation (ECMO) after more than 2 h of cardiopulmonary resuscitation. After 14 h of ECMO support and five days of ventilation, the patient subsequently made a good neurological recovery. At hospital discharge, he had normal cerebral function, and an improving peripheral polyneuropathy affecting distal limbs, with paraesthesia in both feet and reduced coordination and fine motor skills in both hands.

Determining the different phases of torpor from skin- or body temperature data in heterotherms.

Technological innovations have made heat-sensitive data-loggers smaller, more efficient and less expensive, which has led to a growing body of literature that measures the skin- or body temperatures of small animals in their natural environments. Studies of this type on heterothermic endotherms have prompted much debate regarding how to best define 'torpor' expressions from skin- or body temperature data alone. We propose a new quantitative method for defining torpor 'entries', 'arousals' and 'stable torpor periods' whilst comparing the results to 'torpor bout' durations identified using only the torpor cut-off method. By decomposing a torpor bout into 'entries', 'stable torpor periods', and 'active arousals', we avoid biases introduced by using strict threshold temperature values for the onset of torpor, thereby allowing better insight into individual use of torpor. We present our method as an easy-to-use function written in R-code, offering an un-biased and consistent methodology to be applied on skin- or body temperature measurements across datasets and research groups. When testing the function on a large dataset of skin temperature data collected on three bat species in Norway (Plecotus auritus: Nind = 39; Eptesicus nilssonii: Nind = 11; Myotis brandtii: Nind = 10), we identified 461 complete torpor bouts across species. More than 40% of the torpor bouts (Nbouts = 192) did not contain stable torpor periods, because the bats aroused before they had reached a stable skin temperature level. Furthermore, only considering 'torpid' and 'euthermic' temperature values by applying strict cut-off thresholds led to potentially large underestimations of torpor bout durations compared to our quantitative determination of the onset and termination of each torpor bout. We highlight the importance of differentiating between torpor phases, especially for active arousals that can be very energetically expensive and may alter our evaluation of the actual energetic savings gained by an individual employing torpor.

One Cool Guy: Scientific Contributions of John Hayward, Cold Water Pioneer.

John Hayward, PhD (1937-2012), was an early and significant contributor to the understanding of cold water immersion physiology and survival. This article summarizes his work on the 50th anniversary of his first publication in this area. He described areas of high heat loss and emphasized the importance of protecting these areas during cold exposure using the Heat Escape Lessening Posture (HELP) and the potential for heat donation to these areas during rewarming. He described several factors that affect the rate of core cooling, including body composition, behavior (swimming increases cooling whereas the HELP position decreases cooling), wet and wind, and thermal protective garments (dry suits offered much more protection than wet suits). Hayward determined breath-hold duration in children as young as 4 y and had his own heart catheterized for 3 d to complete 3 hypothermia rewarming trials. His work provided early understanding of the cold shock response and ways to mitigate its threat to survival. Hayward provided valuable contributions to prediction models for heat production, heat loss, and core cooling rates in cold water. He also developed a human model for severe hypothermia and patented the UVic Thermofloat Jacket. Finally, as evidence of his stature in the cold physiology community, Hayward was a coauthor of the initial State of Alaska guidelines for the treatment of hypothermia. John Hayward was truly a cold water pioneer.

[Effect of Systematic Graded Rewarming Pattern on All-Cause Mortality of Hypothermic Trauma Patients in Different Time Periods].

Objective To investigate the effect of systematic graded rewarming pattern on all-cause mortality of hypothermic trauma patients in different time periods. Methods A prospective case-control study was carried out for 236 hypothermic trauma patients with modified trauma score<12 in the Emergency Department of the Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2021.The patients were randomly assigned into a systematic graded rewarming group (n=118) and a traditional rewarming group (n=118).The main outcome event was all-cause death within 15 days after trauma,and the secondary outcome event was all-cause death within 3,7,and 30 days after trauma. Results Overall,13.98%(33/236) and 14.83%(35/236) of the patients died within 15 and 30 days after trauma,respectively,and the median survival time of all dead patients was 6 (4,10) days.The systematic graded rewarming group had higher temperature after rewarming for 2 h (P=0.001) and larger temperature change after rewarming intervention (P=0.047) than the traditional rewarming group.The all-cause mortality within 15 days (27.3%vs.72.7%,P=0.005) and 30 days (25.7%vs.74.3%,P=0.002) in the systematic graded rewarming group was lower than that in the traditional rewarming group.Kaplan-Meier analysis showed that the survival time of the patients in the systematic graded rewarming group was longer than that in the traditional rewarming group (P=0.003).Multivariate cox regression analysis indicated that systematic graded rewarming was a strong protective factor for survival time after trauma (HR=0.450, P=0.042).Further Logistic regression analysis for the occurrence of all-cause death in each time period showed that the OR of systematic graded rewarming pattern to all-cause death within 15 days and 30 days after trauma were 0.289 and 0.286,respectively,after adjusting the covariates(P=0.008,P=0.005).The temperature after rewarming for 2 h had a negative correlation with all-cause mortality within 30 days after trauma (OR=0.670, P=0.049). Conclusions Systematic graded rewarming is a protective factor for the survival time of patients with traumatic hypothermia and an independent factor affecting the risk of all-cause death within 15 days and 30 days after trauma.The temperature after rewarming for 2 h is expected to be an independent predictor of all-cause mortality of 30 days after trauma in the patients with hypothermia.The systematic graded rewarming pattern could reduce the mortality of hypothermic trauma patients.

[Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study]. / æ–°ç”Ÿå„¿ç¼ºæ°§ç¼ºè¡€æ€§è„‘ç— ä¸åŒå¤æ¸©æ—¶é—´äºšä½Žæ¸©æ²»ç–—ä¸´åºŠæ•ˆæžœçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming. RESULTS: There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018). CONCLUSIONS: Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

Soluble thrombomodulin ameliorates aberrant hemostasis after rewarming in a rat accidental hypothermia model.

BACKGROUND: Accidental hypothermia (AH) sometimes leads to coagulation disorder, especially in severe AH. We previously demonstrated that intrasplenic platelet activation caused aberrant hemostasis and thrombus formation after rewarming in a murine AH model. However, no study has focused on the appropriate management of platelets causing coagulation activation after rewarming of AH. We investigated whether or not recombinant soluble thrombomodulin (rTM) can suppress thrombosis formation after rewarming using a rat AH model. METHODS: Wistar rats were exposed to an ambient temperature of -20 °C under general anesthesia until their rectal temperature decreased to 26 °C. The Hypo group rats (n = 5) were immediately euthanized, while the Hypo/Re group (n = 5) and rTM group rats (n = 5), which were administered rTM (1 mg/kg) via the tail vein, were rewarmed until the rectal temperature returned to 34 °C and then euthanized 6 h later. Tissue and blood samples were collected from all rats for histopathological and coagulation analyses at euthanasia. RESULTS: There was no significant change in the D-dimer level in the Hypo group rats, while the D-dimer level was significantly elevated at 6 h after rewarming in the Hypo/Re group rats (P = 0.015), and histopathology detected both fibrin and platelets in the renal glomerulus. However, the rTM group rats did not show any elevation of the D-dimer levels at 6 h after rewarming, and no fibrin was noted on histopathology. CONCLUSIONS: rTM may be useful as an appropriate anticoagulant in cases of aberrant hemostasis after rewarming of AH.