End-ischemic pharmacological cocktail treatment to mitigate rewarming/reperfusion injury.

Increasing shortage of donor organs leads to the acceptance of less than optimal grafts for transplantation, up to and including organs donated after circulatory standstill of the donor. Therefore, protective strategies and pharmacological interventions destined to reduce ischemia induced tissue injury are considered a worthwhile focus of research. The present study evaluates the potential of a multidrug pharmacological approach as single flush at the end of static preservation to protect the liver from reperfusion injury. Livers were retrieved from male Wistar rats 20 min after cardiac standstill. The organs were cold stored for 18 h, flushed with 20 ml of saline, kept at room temperature for 20 min, and reperfused at 37 °C with oxygenated Williams E solution. In half of the cases, the flush solution was supplemented with a cocktail containing metformin, bucladesine and cyclosporin A. Upon reperfusion, treated livers disclosed a massive mitigation of hepatic release of alanine aminotransferase and aspartate aminotransferase, along with a significant approximately 50 % reduction of radical mediated lipid peroxidation, caspase activation and release of TNF-alpha. Even after preceding cold preservation, a pharmacological cocktail given as single flush is capable to mitigate manifestations of reperfusion injury in the present model.

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.

[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.

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.

Reduction of amputations of frostbitten limbs by treatment using microwave rewarming.

Drug treatment of limb frostbite injuries is complicated due to the poor delivery of medications to affected tissues. External rewarming of the frostbitten area is risky and does not always result in positive outcomes because the dilatation of superficial vessels with constricted deep vessels can lead to irreversible damage, necrosis, and amputation. One of the techniques to restore perfusion of deep vessels in an affected extremity is rewarming with low-power microwave radiation in a specially designed metal chamber. Below are findings following treatment of 14 volunteers with this technique in 2 Tomsk hospitals during winters of 2018-2021. It is demonstrated that timely, i.e. in the early reactive period, application of microwave radiation and appropriate supportive drug treatment results in positive amputation-free outcomes. The key requirement is prompt thermal insulation of the trauma and no prior exposure to external heat sources.

Successful recovery of severe hypothermia with minimally invasive central catheter.

BACKGROUND: Severe hypothermia can result in malignant arrhythmias or cardiac arrest and require invasive central rewarming modalities due to a core body temperature < 28 °C. Difficult rescue missions can make continuous CPR challenging, but the decrease in oxygen consumption at these low temperatures allows for successful recovery despite the delay. Although other active warming techniques, such as peritoneal lavage, intravascular warming catheter, and renal replacement therapy can be beneficial, the consensus statements recommend extracorporeal life support as the preferred rewarming method. CASE PRESENTATION: A 42-year-old female was found in a pond after presumed exposure for 30-40 min with an outside temperature of 17 °F (-8 °C) and was found to be in ventricular fibrillation. ACLS protocol was then initiated. At the hospital, she was intubated and sedated with continuous CPR during multimodal rewarming, including active internal via the ZOLL Icy catheter. One hour after rewarming, with core temperature above 29 °C, she was defibrillated and achieved ROSC. As she continued to warm, she made purposeful movement and was warmed and maintained at euthermia. She was initiated on antibiotics due to aspiration concerns and titrated off vasopressors with extubation on day 2 of hospitalization. She had mild complaints of extremity numbness and chest pain from compressions prior to discharge on hospitalization day 4. CONCLUSIONS: This case has a successful resuscitation of severe hypothermia associated with cardiac arrest. The patient was warmed at greater than 4 °C/h with a less invasive, quicker and potentially more available approach to warming. With equipment improvements, the ability to provide prolonged CPR while rewarming may suggest that transferring to an extracorporeal life support center is not necessary.

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."

Controlled Oxygenated Rewarming Compensates for Cold Storage-induced Dysfunction in Kidney Grafts.

BACKGROUND: Normothermic machine perfusion (NMP) provides a promising strategy for preservation and conditioning of marginal organ grafts. However, at present, high logistic effort limits normothermic renal perfusion to a short, postponed machine perfusion at site of the recipient transplant center. Thus, organ preservation during transportation still takes place under hypothermic conditions, leading to significantly reduced efficacy of NMP. Recently, it was shown that gentle and controlled warming up of cold stored kidneys compensates for hypothermic induced damage in comparison to end ischemic NMP. This study aims to compare controlled oxygenated rewarming (COR) with continuous upfront normothermic perfusion in a porcine model of transplantation. METHODS: Following exposure to 30 min of warm ischemia, kidneys (n = 6/group) were removed and either cold stored for 8 h (cold storage [CS]), cold stored for 6 h with subsequent controlled rewarming up to 35 °C for 2 h (COR), or directly subjected to 8 h of continuous NMP. Kidney function was evaluated using a preclinical autotransplant model with follow-up for 7 d. RESULTS: NMP and COR both improved renal function in comparison to CS and displayed similar serum creatinine and urea levels during follow-up. COR resulted in less tenascin C expression in the tissue compared with CS, indicating reduced proinflammatory upregulation in the graft by gentle rewarming. CONCLUSIONS: COR seems to be a potential alternative in clinical application of NMP, thereby providing logistic ease and usability.

Heated Humidified Breathing Circuit Rewarming in Hypothermic Patients Post-Cardiopulmonary Bypass-Pilot Study.

OBJECTIVES: Hypothermia on intensive care unit (ICU) admission after cardiac surgery and cardiopulmonary bypass is common. It contributes to postoperative complications including shivering, coagulopathy, increased blood loss and transfusion requirements, morbid cardiac events, metabolic acidosis, increased wound infections, and prolonged hospital length of stay. The current standard of care for rewarming ICU patients is forced air warming blankets. However, high-quality evidence on additional benefit rendered by other warming methods, such as heated humidified breathing circuits (HHBC), is lacking. Therefore, the authors conducted a pilot study to examine whether the addition of HHBC to standard forced air warming blankets in hypothermic patients (≤35°C) admitted to the ICU after cardiac surgery using cardiopulmonary bypass reduced time to normothermia. DESIGN: Prospective study conducted at a single large academic medical center. PARTICIPANTS: The study group was composed of 14 patients who were enrolled prospectively between April 1 and June 14, 2019. The study group was compared with a 2:1 matched retrospective control group. The matched group consisted of 28 patients from a 12-month period from July 1, 2018 June 30, 2019. INTERVENTIONS: Study patients received warming via forced air warming blankets and HHBC and were compared with patients in a control group who received only warming blankets. Time to normothermia, time to extubation, time to normal pH, blood loss, blood transfusions, and coagulation profile laboratory values were compared between the study and control groups. MEASUREMENTS AND MAIN RESULTS: The present study found no statistical difference in time to normothermia, for which the standard-of-care retrospective group achieved normothermia after a median (Q1-Q3) 4.8 (4.0-6.0) hours compared with 4.4 (3.5-5.5) hours in the prospective group receiving HHBC. All secondary outcomes, including time to extubation, time to normal pH, ICU blood product transfusion, chest tube output, and coagulation profile, were similar. CONCLUSIONS: The present pilot study detected a similar time to normothermia, extubation, and normal pH when HHBC were added to standard forced air warming blankets in hypothermic patients (≤35°C) admitted to the ICU after cardiac surgery using cardiopulmonary bypass. A future larger prospective study designed to detect smaller, but clinically meaningful, reductions in the time to key clinical events for patients treated with HHBC is feasible and warranted.

Health Technology Assessment for the Prevention of Peri-Operative Hypothermia: Evaluation of the Correct Use of Forced-Air Warming Systems in an Italian Hospital.

This study investigates the implications of using a system for the maintenance of normothermia in the treatment of patients undergoing surgery, determining whether the FAW (Forced-Air Warming) systems are more effective and efficient than the non-application of appropriate protocols (No Technology). We conducted Health Technology Assessment (HTA) analysis, using both real-world data and the data derived from literature, assuming the point of view of a medium-large hospital. The literature demonstrated that Inadvertent Perioperative Hypothermia (IPH) determines adverse events, such as surgical site infection (FAW: 3% vs. No Technology: 12%), cardiac events (FAW: 3.5% vs. No Technology: 7.6%) or the need for blood transfusions (FAW: 6.2% vs. No Technology: 7.4%). The correct use of FAW allows a medium saving of 16% per patient to be achieved, compared to the non-use of devices. The Cost Effectiveness Value (CEV) is lower in the hypothesis of FAW: it enables a higher efficacy level with a contextual optimization of patients' path costs. The social cost is reduced by around 30% and the overall hospital days are reduced by between 15% and 26%. The qualitative analyses confirmed the results. In conclusion, the evidence-based information underlines the advantages of the proper use of FAW systems in the prevention of accidental peri-operative hypothermia for patients undergoing surgery.

Effect of prewarming on body temperature in short-term bladder or prostatic transurethral resection under general anesthesia: A randomized, double-blind, controlled trial.

Perioperative hypothermia causes postoperative complications. Prewarming reduces body temperature decrease in long-term surgeries. We aimed to assess the effect of different time-periods of prewarming on perioperative temperature in short-term transurethral resection under general anesthesia. Randomized, double-blind, controlled trial in patients scheduled for bladder or prostatic transurethral resection under general anesthesia. Eligible patients were randomly assigned to receive no-prewarming or prewarming during 15, 30, or 45 min using a forced-air blanket in the pre-anesthesia period. Tympanic temperature was used prior to induction of anesthesia and esophageal temperature intraoperatively. Primary outcome was the difference in core temperature among groups from the induction of general anesthesia until the end of surgery. Repeated measures multivariate analysis of covariance modeled the temperature response at each observation time according to prewarming. We examined modeled contrasts between temperature variables in subjects according to prophylaxis. We enrolled 297 patients and randomly assigned 76 patients to control group, 74 patients to 15-min group, 73 patients to 30-min group, and 74 patients to the 45-min group. Temperature in the control group before induction was 36.5 ± 0.5 °C. After prewarming, core temperature was significantly higher in 15- and 30-min groups (36.8 ± 0.5 °C, p = 0.004; 36.7 ± 0.5 °C, p = 0.041, respectively). Body temperature at the end of surgery was significantly lower in the control group (35.8 ± 0.6 °C) than in the three prewarmed groups (36.3 ± 0.6 °C in 15-min, 36.3 ± 0.5 °C in 30-min, and 36.3 ± 0.6 °C in 45-min group) (p < 0.001). Prewarming prior to short-term transurethral resection under general anesthesia reduced the body temperature drop during the perioperative period. These time-periods of prewarming also reduced the rate of postoperative complications.Study Registration Registered at ClinicalTrials.gov (Identifier: NCT03630887).

Vitrification and Nanowarming of Kidneys.

Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled "nanowarming" addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica-coated iron oxide nanoparticles (sIONPs). After cooling at -40 °C min-1 in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min-1 . Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation.

The efficiency of continuous renal replacement therapy for rewarming of patients in accidental hypothermia--An experimental study.

Severe accidental hypothermia carries high mortality and morbidity and is often treated with invasive extracorporeal methods. Continuous veno-venous hemodiafiltration (CVVHDF) is widely available in intensive care units. We sought to provide theoretical basis for CVVHDF use in rewarming of hypothermic patients. CVVHDF system was used in the laboratory setting. Heat balance and transferred heat units were evaluated for the system without using blood. We used 5L of crystalloid solution at the temperature of approximately 25°C, placed in a thermally insulated tank (representing the "central compartment" of a hypothermic patient). Time of warming the central compartment from 24.9 to 30.0°C was assessed with different flow combinations: "blood" (central compartment fluid) 50 or 100 or 150 mL/min, dialysate solution 100 or 1500 mL/h, and substitution fluid 0 or 500 mL/h. The total circulation time was 1535 minutes. There were no differences between heat gain values on the filter depending on blood flow (P = .53) or dialysate flow (P = .2). The mean heating time for "blood" flow rates 50, 100, and 150 mL/min was 113.7 minutes (95% CI, 104.9-122.6 minutes), 83.3 minutes (95% CI, 76.2-90.3 minutes), and 74.7 minutes (95% CI, 62.6-86.9 minutes), respectively (P < .01). The respective median rewarming rate for different "blood" flows was 3.6°C/h (IQR, 3.0-4.2°C/h), 4.8 (IQR, 4.2-5.4°C/h), and 5.4 (IQR, 4.8-6.0°C/h), respectively (P < .01). The dialysate flow did not affect the warming rate. Based on our experimental model, CVVHDF may be used for extracorporeal rewarming, with the rewarming rates increasing achieved with higher blood flow rates.

Maintaining intravenous volume mitigates hypothermia-induced myocardial dysfunction and accumulation of intracellular Ca2.

NEW FINDINGS: What is the central question of this study? Detailed guidelines for volume replacement to counteract hypothermia-induced intravascular fluid loss are lacking. Evidence suggests colloids might have beneficial effects compared to crystalloids. Are central haemodynamic function and level of hypothermia-induced calcium overload, as a marker of cardiac injury, restored by fluid substitution during rewarming, and are colloids favourable to crystalloids? What is the main finding and its importance? Infusion with crystalloid or dextran during rewarming abolished post-hypothermic cardiac dysfunction, and partially mitigated myocardial calcium overload. The effects of volume replacement to support haemodynamic function are comparable to those using potent cardio-active drugs. These findings underline the importance of applying intravascular volume replacement to maintain euvolaemia during rewarming. ABSTRACT: Previous research exploring pathophysiological mechanisms underlying circulatory collapse after rewarming victims of severe accidental hypothermia has documented post-hypothermic cardiac dysfunction and hypothermia-induced elevation of intracellular Ca2+ concentration ([Ca2+ ]i ) in myocardial cells. The aim of the present study was to examine if maintaining euvolaemia during rewarming mitigates cardiac dysfunction and/or normalizes elevated myocardial [Ca2+ ]i . A total of 21 male Wistar rats (300 g) were surface cooled to 15°C, then maintained at 15°C for 4 h, and subsequently rewarmed to 37°C. The rats were randomly assigned to one of three groups: (1) non-intervention control (n = 7), (2) dextran treated (i.v. 12 ml/kg dextran 70; n = 7), or (3) crystalloid treated (24 ml/kg 0.9% i.v. saline; n = 7). Infusions occurred during the first 30 min of rewarming. Arterial blood pressure, stroke volume (SV), cardiac output (CO), contractility (dP/dtmax ) and blood gas changes were measured. Post-hypothermic changes in [Ca2+ ]i were measured using the method of radiolabelled Ca2+ (45 Ca2+ ). Untreated controls displayed post-hypothermic cardiac dysfunction with significantly reduced CO, SV and dP/dtmax . In contrast, rats receiving crystalloid or dextran treatment showed a return to pre-hypothermic control levels of CO and SV after rewarming, with the dextran group displaying significantly better amelioration of post-hypothermic cardiac dysfunction than the crystalloid group. Compared to the post-hypothermic increase in myocardial [Ca2+ ]i in non-treated controls, [Ca2+ ]i values with crystalloid and dextran did not increase to the same extent after rewarming. Volume replacement with crystalloid or dextran during rewarming abolishes post-hypothermic cardiac dysfunction, and partially mitigates the hypothermia-induced elevation of [Ca2+ ]i .

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.

Reduction of Renal Preservation/Reperfusion Injury by Controlled Hyperthermia During Ex Vivo Machine Perfusion.

The possible reno-protective effect of a controlled brief heat-shock treatment during isolated ex vivo machine perfusion of donor grafts prior to reperfusion should be investigated in a primary in vitro study. Porcine kidneys (n = 14) were retrieved after 20 minutes of cardiac standstill of the donor and subjected to 20 hours of static cold storage in University of Wisconsin solution. Prior to reperfusion, kidneys were subjected to 2 hours of reconditioning machine perfusion with gradual increase in perfusion temperature up to 35°C. In half of the kidneys (n = 7), a brief hyperthermic impulse (10 minutes perfusion at 42°C) was implemented in the machine perfusion period. Functional recovery of the grafts was observed upon normothermic reperfusion in vitro. Hyperthermic treatment resulted in a 50% increase of heat shock protein (HSP) 70 and HSP 27 mRNA and was accompanied by ~ 50% improvement of tubular re-absorption of sodium and glucose upon reperfusion, compared with the controls. Furthermore, renal loss of aspartate aminotransferase was significantly reduced to one-third of the controls as was urinary protein loss, evaluated by the albumin to creatinine ratio. It is concluded that ex vivo heat-shock treatment seems to be an easily implementable and promising option to enhance renal self-defense machinery against reperfusion injury after preservation that merits further investigation in preclinical models.

Hibernator-Derived Cells Show Superior Protection and Survival in Hypothermia Compared to Non-Hibernator Cells.

Mitochondrial failure is recognized to play an important role in a variety of diseases. We previously showed hibernating species to have cell-autonomous protective mechanisms to resist cellular stress and sustain mitochondrial function. Here, we set out to detail these mitochondrial features of hibernators. We compared two hibernator-derived cell lines (HaK and DDT1MF2) with two non-hibernating cell lines (HEK293 and NRK) during hypothermia (4 °C) and rewarming (37 °C). Although all cell lines showed a strong decrease in oxygen consumption upon cooling, hibernator cells maintained functional mitochondria during hypothermia, without mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential decline or decreased adenosine triphosphate (ATP) levels, which were all observed in both non-hibernator cell lines. In addition, hibernator cells survived hypothermia in the absence of extracellular energy sources, suggesting their use of an endogenous substrate to maintain ATP levels. Moreover, hibernator-derived cells did not accumulate reactive oxygen species (ROS) damage and showed normal cell viability even after 48 h of cold-exposure. In contrast, non-hibernator cells accumulated ROS and showed extensive cell death through ferroptosis. Understanding the mechanisms that hibernators use to sustain mitochondrial activity and counteract damage in hypothermic circumstances may help to define novel preservation techniques with relevance to a variety of fields, such as organ transplantation and cardiac arrest.

An open-label, randomised controlled trial on the effectiveness of the Orve + wrap® versus Forced Air Warming in restoring normothermia in the postanaesthetic care unit.

AIMS AND OBJECTIVES: To determine the clinical effectiveness and safety of the Orve + wrap® thermal blanket. BACKGROUND: Inadvertent perioperative hypothermia is a common problem in postanaesthetic care units and can have significant effects on patients' postoperative morbidity. Despite its commercial availability, there is no clinical evidence on the effectiveness of Orve + wrap®. DESIGN: A single centre prospective, open-label, noninferiority randomised controlled trial. METHODS: Postoperative hypothermic (35.0-35.9°C) patients who had undergone elective surgery were randomised to receive either Orve + wrap® or Forced Air Warming during their PACU stay. Patient temperatures were recorded every 10 min using zero-heat-flux thermometry. This study is reported using CONSORT Extension checklist for noninferiority and equivalence trials. RESULTS: Between December 2016-October 2018, 129 patients were randomised to receive either Orve + wrap® blanket (n = 65, 50.3%) or Forced Air Warming (n = 64, 49.7%). The mean 60-min postoperative temperature of patients receiving Orve + wrap® blanket was 36.2 and 36.3°C for the patients receiving Forced Air Warming. The predefined noninferiority margin of a mean difference in temperature of 0.3°C was not reached between the groups at 60 min. Additionally, there were no statistical differences between adverse event rates across these groups. CONCLUSIONS: In the context of this study, warming patients with the Orve + wrap® was noninferior to Forced Air Warming. There were comparable rates of associated postoperative consequences of warming (shivering, hypotension, arrhythmias or surgical site infections), between the groups. RELEVANCE TO CLINICAL PRACTICE: The Orve + wrap® potentially provides an alternative warming method to Forced Air Warming for patients requiring short-term postoperative warming. However, there are still a number of unknowns regarding the Orve + wrap® performance and further exploration is required.

The efficacy of HBOC-201 in ex situ gradual rewarming kidney perfusion in a rat model.

Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome to sudden rewarming to normothermic. However, the identification of an oxygen carrier that could function at a temperature range from 4 to 7°C or whether it is necessary to use oxygen carrier during kidney rewarming, remains unresolved. This study was designed to test the use of a hemoglobin-based oxygen carrier (HBOC) during gradual kidney rewarming as an alternative to simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into the control and the HBOC group. In the control group, no oxygen carrier was used during rewarming perfusion and the perfusion solution was oxygenated only by applying diffused carbogen flow. The protocol mimicked a donor after circulatory death (DCD) kidney transplantation, where after 30 minutes warm ischemia and 120 minutes cold storage in University of Wisconsin solution, the DCD kidneys underwent gradual rewarming from 10 to 37°C during 90 minutes with or without HBOC. This was followed by 30 minutes of warm ischemia in room temperature to mimic the anastomosis time and 120 minutes of reperfusion at 37°C to mimic the early post-transplant state of the graft. The HBOC group demonstrated superior kidney function which was highlighted by higher ultrafiltrate production, better glomerular filtration rate and improved sodium reabsorption. There was no significant difference between the 2 groups regarding the hemodynamics, tissue injury, and adenosine triphosphate levels. In conclusion, this study suggests better renal function recovery in DCD kidneys after rewarming with HBOC compared to rewarming without an oxygen carrier.

Preventing hypothermia in outpatient plastic surgery by self-warming or forced-air-warming blanket: A randomised controlled trial.

BACKGROUND: In our outpatient post anaesthesia unit patients reported that they were feeling cold with or without shivering. Anaesthetic agents cause reduced thermoregulation, initially by redistribution of blood flow from core to periphery, later by negative balance between thermogenesis and heat loss. Even mild peri-operative hypothermia increases the risk of surgical wound infections, bleeding, impaired cardiac function, shivering, and decreases comfort. OBJECTIVE(S): We aimed to evaluate which of our current active warming measures, self-warming blanket or forced-air-warming blanket, were most effective in preventing inadvertent intraoperative heat loss. Secondarily, we assessed whether they prevented inadvertent peri-operative hypothermia when defined as core body temperature below 36 °C. DESIGN: Randomised controlled trial, parallel group design. SETTING: Aleris Solsiden hospital for outpatient surgery, Trondheim, Norway, from March to June 2016. PATIENTS: A total of 112 consecutive patients planned for outpatient plastic surgery. Reasons for noninclusion: failing to meet the criteria for outpatient surgery according to the standard of the national society of anaesthesiology. INTERVENTION(S): Patients were randomised to active warming by a self-warming blanket or a forced-air-warming blanket. All patients received routine measures to prevent hypothermia with a high temperature in the operation theatres, prewarmed fluids, cotton blankets and surgical draping outside the surgical field. MAIN OUTCOMES: Temperature, measured pre-operatively, every 10 min during general anaesthesia and postoperatively with a zero-heat-flux temperature sensor. RESULTS: Core temperature was significantly lower in the self-warming blanket compared with the forced-air-warming blanket group during anaesthesia, P less than 0.0001. Hypothermia (<36 °C) was recorded in 47%, n = 22, patients in the self-warming blanket group and 25%, n = 16, in the forced-air-warming blanket group during the registration period, P = 0.02. CONCLUSION: An underbody forced-air-warming blanket reduced heat loss to a greater extent than a self-warming blanket. But none of the interventions were sufficient to prevent inadvertent peri-operative hypothermia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03163563.