Prolonged critical avalanche burial for nearly 23 h with severe hypothermia and severe frostbite with good recovery: a case report.

BACKGROUND: Accidental hypothermia with severe frostbite is a rare combination of injuries with a high risk for long-term sequelae. There are widely accepted recommendations for the management of avalanche victims and for frostbite treatment, but no recommendation exists for the treatment of frostbite in severe hypothermic patients, specifically for the management of hypothermic avalanche victims presenting with frostbite. CASE PRESENTATION: We present a case of a previously healthy, 53-year-old male skier who was critically buried by an avalanche at 2300 m of altitude at an ambient temperature of - 8 °C for nearly 23 h. The victim was found with the right hand out of the snow and an air connection to outside. He was somnolent with Glasgow Coma Scale 11 (Eye 4, Verbal 2, Motor 5) and spontaneously breathing, in a severely hypothermic state with an initial core temperature of 23.1 °C and signs of cold injuries in all four extremities. After rescue and active external forced air rewarming in the intensive care unit, the clinical signs of first-degree frostbite on both feet and the left hand vanished, while third- to fourth-degree frostbite injuries became apparent on all fingers of the right hand. After reaching a core body temperature of approximately 36 °C, aggressive frostbite treatment was started with peripheral arterial catheter-directed thrombolysis with alteplase, intravenous iloprost, ibuprofen, dexamethasone and regional sympathicolysis with a right-sided continuous axillary block. After ten months, the patient had no tissue loss but needed neuropathic pain treatment with pregabalin. CONCLUSION: The combination of severe accidental hypothermia and severe frostbite is rare and challenging, as drug metabolism is unpredictable in a hypothermic patient and no recommendations for combined treatment exist. There is general agreement to give hypothermia treatment the priority and to begin frostbite treatment as early as possible after full rewarming of the patient. More evidence is needed to identify the optimal dosage and time point to initiate treatment of frostbite in severely hypothermic patients. This should be taken into consideration by future treatment recommendations.

[Reducing the Incidence of Postoperative Hypothermia in Patients Undergoing Robotic-Assisted Mitral Valve Surgery].

BACKGROUND & PROBLEMS: Post-operation hypothermia tends to induce complications. Sixty percent of robotic-assisted mitral valve surgery patients experienced hypothermia while admitted to our intensive care unit (ICU), resulting in prolonged ICU stays and 57% (eight) of those patients with hypothermia also experiencing cardiac arrhythmia. The causes of hypothermia in our ICU included low temperature in the operating room, delayed initiation of blanket coverage after surgery, and lack of postoperative thermal blankets, insufficient cardiopulmonary bypass rewarming time, cold ICU beds, lack of in-service training for hypothermia, and lack of procedure auditing. PURPOSE: This intervention was designed to reduce the incidence of hypothermia in ICU patients undergoing robotic-assisted mitral valve surgery upon ICU admission from 60% to 36% and the one-hour hypothermia rate from 43.3% to 26%. RESOLUTIONS: We implemented several measures including increasing the room temperature, pre-heating the ICU bed, achieving team consensus regarding prolonging the rewarming time after cardiopulmonary bypass, establishing a blanket warming area for postoperative patient use, and holding in-service training to enhance the awareness of the nurses were implemented. RESULTS: The incidence of hypothermia in ICU patients receiving robotic-assisted mitral valve surgery upon ICU admission decreased from 60% to 19.4%, while the one-hour hypothermia rate decreased from 43.3% to 19.4%. CONCLUSIONS: Using systemic interprofessional collaboration, combined thermal care can be achieved to significantly reduce the incidence of postoperative hypothermia in patients undergoing robotic-assisted mitral valve surgeries resulting in higher patient care quality and shorter ICU stays. We recommend applying this combined method to improve the quality of perioperative care for long-duration and major surgical procedures that involve large postoperative wounds and for patients who may require wider exposure during their operation.

Extracorporeal Rewarming Is Associated With Increased Survival Rate in Severely Hypothermic Patients With Preserved Spontaneous Circulation.

Treatment recommendations for rewarming patients in severe accidental hypothermia with preserved spontaneous circulation have a weak evidence due to the absence of randomized clinical trials. We aimed to compare the outcomes of extracorporeal versus less-invasive rewarming of severely hypothermic patients with preserved spontaneous circulation. We conducted a multicenter retrospective study. The patient population was compiled based on data from the HELP Registry, the International Hypothermia Registry, and a literature review. Adult patients with a core temperature <28°C and preserved spontaneous circulation were included. Patients who underwent extracorporeal rewarming were compared with patients rewarmed with less-invasive methods, using a matched-pair analysis. The study population consisted of 50 patients rewarmed extracorporeally and 85 patients rewarmed with other, less-invasive methods. Variables significantly associated with survival included: lower age; outdoor cooling circumstances; higher blood pressure; higher PaCO 2 ; higher BE; higher HCO 3 ; and the absence of comorbidities. The survival rate was higher in patients rewarmed extracorporeally ( p = 0.049). The relative risk of death was twice as high in patients rewarmed less invasively. Based on our data, we conclude that patients in severe accidental hypothermia with circulatory instability can benefit from extracorporeal rewarming without an increased risk of complications.

The effect of rewarming on hemodynamic parameters and arterial blood gases of patients after open-heart surgery: A randomized controlled trial.

INTRODUCTION: Hypothermia after open-heart surgery can have potential side effects for patients. AIM: This study aimed to examine the effects of rewarming on patients' hemodynamic and arterial blood gases parameters after open-heart surgery. METHODS: This randomized controlled trial was performed in 2019 on 80 patients undergoing open-heart surgery at Tehran Heart Center, Iran. The subjects were consecutively recruited and randomly assigned to an intervention group (n=40) and a control group (n=40). After the surgery, the intervention group was warmed with an electric warming mattress while the control group warmed using a simple hospital blanket. The hemodynamic parameters of the two groups were measured 6 times and arterial blood gas was measured 3 times. Data were analyzed by independent samples t and Chi-squared tests, and repeated measures analysis. RESULTS: Before the intervention, the two groups did not significantly differ in terms of hemodynamic and blood gas parameters. However, the two groups were significantly different in the mean heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, temperature, right and left lung drainage in the first half-hour, and the first to fourth hours after the intervention (p < 0.05). Furthermore, there was a significant difference between the mean arterial oxygen pressure of the two groups during and after rewarming (P <0.05). CONCLUSION: Rewarming of patients after open-heart surgery can significantly affect hemodynamic and arterial blood gas parameters. Therefore, rewarming methods can be used safely to improve the patients' hemodynamic parameters after open-heart surgery.

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.

Veno-Venous Extracorporeal Rewarming Using Dual-Lumen Cannula in Accidental Hypothermia.

Accidental hypothermia with a core temperature below 28°C is associated with an increased risk of hemodynamic instability. It is difficult to predict which patients will survive with a favorable neurologic outcome; therefore, decision-making regarding extracorporeal support is not straightforward. We report a case of rewarming using veno-venous dual-lumen cannula as an alternative to veno-arterial support with full recovery and normal neurologic examination. In centers where extracorporeal membrane oxygenation is available, rewarming using veno-venous dual-lumen extracorporeal support may be a useful strategy to mitigate the risks associated with veno-arterial extracorporeal support.

The cold receptor TRPM8 activation leads to attenuation of endothelium-dependent cerebral vascular functions during head cooling.

Using the cranial window technique, we investigated acute effects of head cooling on cerebral vascular functions in newborn pigs. Head cooling lowered the rectal and extradural brain temperatures to 34.3 ± 0.6°C and 26.1 ± 0.6°C, respectively. During the 3-h hypothermia period, responses of pial arterioles to endothelium-dependent dilators bradykinin and glutamate were reduced, whereas the responses to hypercapnia and an endothelium-independent dilator sodium nitroprusside (SNP) remained intact. All vasodilator responses were restored after rewarming, suggesting that head cooling did not produce endothelial injury. We tested the hypothesis that the cold-sensitive TRPM8 channel is involved in attenuation of cerebrovascular functions. TRPM8 is immunodetected in cerebral vessels and in the brain parenchyma. During normothermia, the TRPM8 agonist icilin produced constriction of pial arterioles that was antagonized by the channel blocker AMTB. Icilin reduced dilation of pial arterioles to bradykinin and glutamate but not to hypercapnia and SNP, thus mimicking the effects of head cooling on vascular functions. AMTB counteracted the impairment of endothelium-dependent vasodilation caused by hypothermia or icilin. Overall, mild hypothermia produced by head cooling leads to acute reversible reduction of selected endothelium-dependent cerebral vasodilator functions via TRPM8 activation, whereas cerebral arteriolar smooth muscle functions are largely preserved.

Effect of nurse-initiated forced-air warming blanket on the reduction of hypothermia complications following coronary artery bypass grafting: a randomized clinical trial.

AIMS: To evaluate the effect of postoperative forced-air warming (FAW) on the incidence of excessive bleeding (ExB), arrhythmia, acute myocardial infarction (AMI), and blood product transfusion in hypothermic patients following on-pump CABG and compare temperatures associated with the use of FAW and warming with a sheet and wool blanket. METHODS AND RESULTS: A randomized clinical trial conducted with 200 patients undergoing isolated on-pump CABG from January to November 2018. Patients were randomly assigned into an Intervention Group (IG, FAW, n = 100) and Control Group (CG, sheet and blanket, n = 100). The tympanic temperature of all patients was measured over a 24-h period. ExB was the primary outcome, while arrhythmia, AMI, and blood product transfusion were secondary outcomes. The effect of the interventions on the outcomes was investigated through using bivariate logistic regression, with a level of significance of 5%. The IG was 79% less likely to experience bleeding than the CG [odds ratio (OR) = 0.21, confidence interval (CI) 95% 0.12-0.39, P < 0.001]; the occurrence of AMI in the IG was 94% lower than that experienced by the CG (OR = 0.06, CI 95% 0.01-0.48, P < 0.001); and the IG was also 77% less likely to experience arrhythmia than the CG (OR = 0.23, CI 95% 0.12-0.47, P < 0.001); no difference was found between groups in terms of blood product transfusion (P < 0.279). CONCLUSIONS: These findings show that FAW can be used following CABG until patients reach normothermia to avoid undesirable clinical outcomes. TRIAL REGISTRATION: REBeC RBR-5t582g.

Is prehospital use of active external warming dangerous for patients with accidental hypothermia: a systematic review.

BACKGROUND: Optimal prehospital management and treatment of patients with accidental hypothermia is a matter of frequent debate, with controversies usually revolving around the subject of rewarming. The rule of thumb in primary emergency care and first aid for patients with accidental hypothermia has traditionally been to be refrain from prehospital active rewarming and to focus on preventing further heat loss. The potential danger of active external rewarming in a prehospital setting has previously been generally accepted among the emergency medicine community based on a fear of potential complications, such as "afterdrop", "rewarming syndrome", and "circum-rescue collapse". This has led to a reluctancy from health care providers to provide patients with active external rewarming outside the hospital. Different theories and hypotheses exist for these physiological phenomena, but the scientific evidence is limited. The research question is whether the prehospital use of active external rewarming is dangerous for patients with accidental hypothermia. This systematic review intends to describe the acute unfavourable adverse effects of active external rewarming on patients with accidental hypothermia. METHODS: A literature search of the Cochrane Library, MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL], and SveMed+ was carried out, and all articles were screened for eligibility. All article formats were included. RESULTS: Two thousand three hundred two articles were screened, and eight articles met our search criteria. Three articles were case reports or case series, one was a prospective study, two were retrospective studies, one article was a literature review, and one article was a war report from the Napoleonic Wars. CONCLUSIONS: One of the main findings in this article was the poor scientific quality and the low number of articles meeting our inclusion criteria. When conducting this review, we found no scientific evidence of acceptable quality to prove that the use of active external rewarming is dangerous for patients with accidental hypothermia in a prehospital setting. We found several articles claiming that active external rewarming is dangerous, but most of them do not cite references or provide evidence.

A novel ECG-biomarker for cardiac arrest during hypothermia.

BACKGROUND: Treatment of arrhythmias evoked by accidental or therapeutic hypothermia and rewarming remains challenging. We aim to find an ECG-biomarker that can predict ventricular arrhythmias at temperatures occurring in therapeutic and accidental hypothermia. MAIN BODY: Evaluation of ECG-data from accidental and therapeutic hypothermia patients and experimental data on ECG and ventricular fibrillation (VF) threshold in hypothermic New Zealand White Rabbits. VF threshold was measured in rabbit hearts cooled to moderate (31 °C) and severe (17 °C) hypothermia. QRS-interval divided by corrected QT-interval (QTc) was calculated at same temperatures. Clinical QRS/QTc data were obtained after a systematic literature review. Rabbit QRS/QTc values correlated with risk for VF (correlation coefficient: 0.97). Human QRS/QTc values from hypothermic patients, showed similar correlation with risk for ventricular fibrillation in the experimental data (correlation coefficient: 1.00). CONCLUSIONS: These calculations indicate that QRS/QTc has potential as novel biomarker for predicting risk of hypothermia-induced cardiac arrest. Our findings apply both to victims of accidental hypothermia and to patients undergoing therapeutic hypothermia during surgery or after e.g. cardiac arrest.

Association between rewarming duration and neurological outcome in out-of-hospital cardiac arrest patients receiving therapeutic hypothermia.

AIM: The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h-0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3-5. RESULTS: The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79-0.99; p =  0.032]. CONCLUSION: A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH.

Mechanisms Associated with the Adverse Vascular Consequences of Rapid Posthypothermic Rewarming and Their Therapeutic Modulation in Rats.

We previously demonstrated that rapid posthypothermic rewarming in noninjured animals was capable of damaging cerebral arterioles both at endothelial and smooth muscle levels. Such adverse consequences could be prevented with antioxidants, suggesting the involvement of free radicals. In this study, we further investigate the mechanisms associated with free radicals production by using two radical scavengers, superoxide dismutase (SOD) and catalase. Employing rats, the cerebral vascular response was evaluated at 2, 3, and 4 hours after onset of hypothermia. Before rapid rewarming, SOD treatment, but not catalase, preserved the NO-mediated dilation induced by acetylcholine (ACh). On the contrary, catalase preserved the hypercapnia-induced relaxation of the smooth muscle cells, whereas SOD offered only partial protection. Adding SOD to catalase treatment offered no additional benefit. These results suggest that rapid posthypothermic rewarming impairs ACh- and hypercapnia-induced vasodilation through different subcellular mechanisms. In the case of diminished vascular response to ACh, it appears to act on the endothelial front primarily by superoxide anions, as evidenced by its full preservation after SOD treatment. In terms of impaired dilation to hypercapnia, hydrogen peroxide and/or its derivatives are the likely candidates in targeting the smooth muscle cells. The partial protection of SOD to hypercapnia-induced dilation is believed to be the reduced amount of superoxide that would otherwise spontaneously dismutate to produce hydrogen peroxide. Although SOD exerts some indirect influence on the hydrogen peroxide production downstream, catalase apparently has no influence on upstream superoxide production.

Risk of Burns During Active External Rewarming for Accidental Hypothermia.

This article describes 3 incidents in which therapeutic or experimental warming of cold individuals caused first- to third-degree burns to the skin. Mechanisms for these injuries are considered. We conclude that active external rewarming of the trunk of a cold patient in the field can be administered safely and burn risk reduced if 1) manufacturer instructions are followed; 2) insulation is placed between the skin the and heat source; and 3) caregivers make regular efforts to observe heated skin for possible pending burn injury. Direct inspection is mandatory for the skin of areas that are on top of a heat source when the patient is lying on the heat source.

Hypothermia-rewarming: A Double-edged sword?

Hypothermia is a condition in which the body's core temperature drops below 35.0 °C. Hypothermia is the opposite of hyperthermia, which the metabolism and body functions are abnormal. Severe hypothermia is a life-threatening problem that may cause atrial and ventricular dysrhythmias, coagulopathy, cardiac, and central nervous system depression. What is worse, it is fatal when untreated or treated improperly. Accidental deaths due to hypothermia resulting from immersion in cold water, especially involving naval fighters and maritime victims have occurred continually in the past years. Currently, the treatment of hypothermia has become a research focus. Rewarming is the only approach that should be considered for hypothermia treatment. However, the treatment is of low efficiency, and few active rewarming cases have been reported. It is well known that timely reperfusion is the best way to save the lives of patients with ischemia. Similarly, reoxygenation is effective for hypoxia. However, several studies have identified that improper reperfusion of ischemic tissues and reoxygenation of hypoxic tissues give rise to further injury. Analogically, this study attempts to propose the hypothesis that hypothermia-rewarming injury may also exist. When suffered from hypothermia, both the blood circulation and the oxygen supply in the body will be affected in a deficient state, an injury may also appear in the improper rewarming process. In a word, hypothermia-rewarming may be a double-edged sword.

Slow as Compared to Rapid Rewarming After Mild Hypothermia Improves Survival in Experimental Shock.

BACKGROUND: Accidental hypothermia following trauma is an independent risk factor for mortality. However, in most experimental studies, hypothermia clearly improves outcome. We hypothesized that slow rewarming is beneficial over rapid rewarming following mild hypothermia in a rodent model of hemorrhagic shock. MATERIALS AND METHODS: We subjected 32 male Wistar rats to severe hemorrhagic shock (25-30 mmHg for 30 min). Rats were assigned to four experimental groups (normothermia, hypothermia, rapid rewarming [RW], and slow RW). During induction of severe shock, all but the normothermia group were cooled to 34°C. After 60 min of shock, rats were resuscitated with Ringer's solution. The two RW groups were rewarmed at differing rates (6°C/h versus 2°C/h). RESULTS: Slow RW animals exhibit a significantly prolonged survival compared with the rapid RW animals (P < 0.05). Nevertheless, hypothermic animals show a significant survival benefit as compared to all other experimental groups. Whereas seven animals of the hypothermia group survived to the end of the experiment, none of the other animals did (P < 0.001). No significant differences were found regarding acid base status, metabolism, parameters of organ injury, and coagulation. CONCLUSIONS: The results indicate that even slow RW with 2°C/h may be still too fast in the setting of experimental hemorrhage. Too rapid rewarming may result in a loss of the protective effects of hypothermia. As rewarming is ultimately inevitable in patients with trauma, potential effects of rewarming on patient outcome should be further investigated in clinical studies.

The effects of a forced-air warming system plus electric blanket for elderly patients undergoing transurethral resection of the prostate: A randomized controlled trial.

BACKGROUND: Perioperative inadvertent hypothermia in elderly urology patients undergoing transurethral resection of the prostate (TURP) is a well-known serious complication, as it increases the risk of myocardial ischemia, blood loss, and surgical wound infection. We conducted this prospective randomized controlled trial to evaluate the combined effect of a forced-air warming system and electric blanket in elderly TURP patients. METHODS: Between January 2015 and October 2017, we recruited 443 elderly male patients undergoing elective TURP with subarachnoid blockade (SAB). These were randomly divided into 3 groups: group E (intraoperative warming using electric blankets set to 38°C; n = 128); group F (intraoperative warming using a forced-air warmer set to 38°C; n = 155) and group FE (intraoperative warming using a forced-air warmer plus electric blankets, both set to 38°C; n = 160). The primary outcome was shivering and their grades. Hemodynamic changes, esophageal temperature, recovery time, incidences of adverse effects, and patient and surgeon satisfaction were also recorded. RESULTS: Baseline characteristics showed no significant differences when compared across the 3 groups (P >.05). Compared with groups E and F, both HR and mean arterial pressure (MAP) in group FE were significantly decreased from T6 to T10 (P <.05). Compared with groups E and F, esophageal temperature in group FE increased significantly from T5 to T10 (P <.05). Compared with group E, esophageal temperature in group F was significantly increased from T5 to T10 (P <.05). Compared with groups F and FE, post-anesthesia care unit (PACU) recovery time was longer in group E, while compared with group F, PACU recovery time was shorter in group FE (P <.05). Compared to patients in groups E and F, those in group FE had a significantly lower incidence of arrhythmia and shivering (P <.05). The number of patients with shivering grades 0 to 3 was higher in group E than in other groups, while the number of patients with shivering grade 2 was significantly higher in group F than in group FE (P <.05). Patient and surgeon satisfaction scores were higher in group FE than in groups E and F (P <.05). CONCLUSIONS: Use of a forced-air warming system combined with an electric blanket was an effective method with which to retain warmth among elderly TURP patients.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Methods: Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. Results: H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. Conclusions: The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols limit DNA damage, but only SUL-109 also prevented protein nitrosylation in tubular cells. Therefore SUL-109 offers a promising therapeutic strategy to preserve kidney mitochondrial function.

Role of superoxide ion formation in hypothermia/rewarming induced contractile dysfunction in cardiomyocytes.

Rewarming following accidental hypothermia is associated with circulatory collapse due primarily to impaired cardiac contractile (systolic) function. Previously, we found that reduced myofilament Ca2+ sensitivity underlies hypothermia/rewarming (H/R)-induced cardiac contractile dysfunction. This reduced Ca2+ sensitivity is associated with troponin I (cTnI) phosphorylation. We hypothesize that H/R induces reactive oxygen species (ROS) formation in cardiomyocytes, which leads to cTnI phosphorylation and reduced myofilament Ca2+ sensitivity. To test this hypothesis, we exposed isolated rat cardiomyocytes to a 2-h period of severe hypothermia (15 °C) followed by rewarming (35 °C) with and without antioxidant (TEMPOL) treatment. Simultaneous measurements of cytosolic Ca2+ ([Ca2+]cyto) and contractile (sarcomere shortening) responses indicated that H/R-induced contractile dysfunction and reduced Ca2+ sensitivity was prevented in cardiomyocytes treated with TEMPOL. In addition, TEMPOL treatment blunted H/R-induced cTnI phosphorylation. These results support our overall hypothesis and suggest that H/R disrupts excitation-contraction coupling of the myocardium through a cascade of event triggered by excessive ROS formation during hypothermia. Antioxidant treatment may improve successful rescue of accidental hypothermia victims.

Effects of hypothermia and rewarming on cardiovascular autonomic control in vivo.

Rewarming from accidental hypothermia is associated with cardiovascular dysfunction that complicates rewarming and contributes to a high mortality rate. We investigated autonomic cardiovascular control, as well as the separate effects of cooling, hypothermia, and rewarming on hemodynamic function, aiming to provide knowledge of the pathophysiology causing such complications in these patients. A rat model designed for circulatory studies during cooling, hypothermia (15°C), and rewarming was used. Spectral analysis of diastolic arterial pressure and heart rate allowed assessment of the autonomic nervous system. Hemodynamic variables were monitored using a conductance catheter in the left ventricle and a pressure transducer connected to the left femoral artery. Sympathetic cardiovascular control was reduced after rewarming. Stroke volume increased during cooling but decreased during stable hypothermia and did not normalize during rewarming. Despite autonomic dysfunction, total peripheral resistance increased during cooling and did not normalize after rewarming. The present data show that sympathetic cardiovascular control is reduced by hypothermia and rewarming. A simultaneous systolic dysfunction is seen in rewarmed animals, caused by reduced filling of the left ventricle and impaired contractile function, in the presence of normal diastolic function. These findings show that dysfunction of the efferent sympathetic nervous system could be instrumental in development of rewarming shock. NEW & NOTEWORTHY The present study shows impaired autonomic control of cardiovascular function after rewarming from severe hypothermia. In victims of accidental hypothermia, rewarming shock is a much feared and lethal complication. The pathophysiology causing such cardiovascular collapse appears complex. Our findings indicate that dysfunction of the autonomic nervous system is an important part of the pathophysiology. Thus the present study gives novel information, important for further development of treatment strategies in this patient group.

Efficacy of different cooling technologies for therapeutic temperature management: A prospective intervention study.

BACKGROUND: Mild therapeutic hypothermia (32-36 °C) is associated with improved outcomes in patients with brain injury after cardiac arrest (CA). Various devices are available to induce and maintain hypothermia, but few studies have compared the performance of these devices. We performed a prospective study to compare four frequently used cooling systems in inducing and maintaining hypothermia followed by controlled rewarming. METHODS: We performed a prospective multi-centered study in ten ICU's in three hospitals within the UPMC health system. Four different cooling technologies (seven cooling methods in total) were studied: two external water-circulating cooling blankets (Meditherm® and Blanketrol®), gel-coated adhesive cooling pads (Arctic Sun®), and endovascular cooling catheters with balloons circulating ice-cold saline (Thermogard®). For the latter system we studied three different types of catheter with two, three or four water-circulating balloons, respectively. In contrast to previous studies, we not only studied the cooling rate (i.e., time to target temperature) in the induction phase, but also the percentage of the time during the maintenance phase that temperature was on target ±0.5 °C, and the efficacy of devices to control rewarming. We believe that these are more important indicators of device performance than induction speed alone. RESULTS: 129 consecutive patients admitted after CA and treated with hypothermia were screened, and 120 were enrolled in the study. Two researchers dedicated fulltime to this study monitored TH treatment in all patients, including antishivering measures, additional cooling measures used (e.g. icepacks and cold fluid infusion), and all other issues related to temperature management. Baseline characteristics were similar for all groups. Cooling rates were 2.06 ±â€¯1.12 °C/h for endovascular cooling, 1.49 ±â€¯0.82 for Arctic sun, 0.61 ±â€¯0.36 for Meditherm and 1.22 ±â€¯1.12 for Blanketrol. Time within target range ±0.5 °C was 97.3 ±â€¯6.0% for Thermogard, 81.8 ±â€¯25.2% for Arctic Sun, 57.4 ±â€¯29.3% for Meditherm, and 64.5 ±â€¯20.1% for Blanketrol. The following differences were significant: Thermogard vs. Meditherm (p < 0.01), Thermogard vs. Blanketrol (p < 0.01), and Arctic Sun vs. Meditherm (p < 0.02). No major complications occurred with any device. CONCLUSIONS: Endovascular cooling and gel-adhesive pads provide more rapid hypothermia induction and more effective temperature maintenance compared to water-circulating cooling blankets. This applied to induction speed, but (more importantly) also to time within target range during maintenance.