Reverse Therapy: Impact of Hyperthermia and Rewarming on Newborn Outcomes.

Therapeutic hypothermia is now well established to improve neurodevelopmental outcomes after hypoxic-ischemic encephalopathy (HIE). Although the overall principles of treatment are now well established, many smaller questions are unclear. The potential impact of reversal of hypothermia therapy and the effect of high temperatures on recovery of the neurovascular unit after therapeutic hypothermia for HIE has received relatively little attention. This article will address the effects of hypoxia-ischemia and rewarming and increased temperatures on the neurovascular unit in preclinical and clinical models.

Intermittent hemodialysis as a rewarming strategy for severe hypothermia in patients without renal failure: a case report.

This case report highlights the effective use of intermittent hemodialysis (IHD) in warming a 71-year-old female patient with severe hypothermia who presented with a rectal temperature of 25 °C and signs of hemodynamic instability. The patient, found unconscious after prolonged exposure to cold exacerbated by alcohol consumption, initially showed some improvement in core temperature through active external rewarming methods. However, soon, her temperature plateaued at 27 °C. Patient was deemed unsuitable for extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) due to her age, and urgent IHD was initiated. This approach resulted in a stable increase in core temperature at approximately 2.0 °C/hr, along with normalization of lactic acidosis, creatinine phosphokinase, and correction of electrolyte imbalances, culminating in her full recovery and discharge after seven days in the hospital.After reviewing this case alongside similar ones from before, this case report highlights the efficacy and safety of IHD as an efficient, readily available, and less invasive method for rewarming moderate to severe hypothermic patients who are hemodynamically unstable patients but do not have cardiac arrest or renal dysfunction. IHD is especially useful when less invasive cooling devices (Artic Sun/ CoolGard) are not available or more invasive extracorporeal life support options (ECMO/ CPB) are either not indicated or unavailable. IHD can also help improve concurrent electrolyte imbalances and/or toxin buildup. The report further emphasizes the necessity of monitoring for potential complications, such as post-dialysis hypophosphatemia and rebound hyperkalemia, following successful rewarming.

The Outcome of Walking Cold Patients with Potential Mild Hypothermia to Safety-A Mountain Rescue Case Series.

INTRODUCTION: Some experts recommend that ambulant hypothermic patients should be rewarmed, fed, and not permitted to exercise for 30 min because of concerns that afterdrop can cause cardiac instability. We investigated the outcome of ambulant hypothermic patients in a case series from mountain rescue teams in Great Britain. METHODS: A questionnaire was used to collect information on a series of adult patients with a clinical diagnosis of mild hypothermia. All patients were alert on the AVPU scale and evacuated by walking from the mountain. The outcome measures were survival or a change in management because of medical deterioration during evacuation. RESULTS: A series of 108 eligible cases were reported over a 5-year period. When rescuers arrived on the scene, 98 (91%) patients were stationary, and 10 (9%) were still mobile. Thirty-eight (39%) of the stationary cases were walked immediately off the mountain without any on-scene delay. In the remaining 60 (61%) stationary cases, the decision was taken to delay evacuation to provide food, drinks, and additional clothing. In 3 cases, the use of heat packs indicated an intention to actively rewarm. In cases where the on-scene time was reported, 27 (79%) were known to be mobile again within 20 min. All patients survived, and no adverse medical events occurred in all 108 cases. CONCLUSIONS: In this study, no adverse events occurred because of immediate mobilization, suggesting that in these cases, there appears to be minimal risk of early activity.

Cold Injury.

Cold injury has been documented for centuries and remains a concern for military personnel, winter recreationalists, and urban homeless populations. Treatment advances in the last decades have included thrombolytic and prostaglandin therapies however the mainstay remains early recognition and rapid rewarming. This chapter focuses on frostbite, with a brief overview of other cold related conditions.

Environmental Hypothermia.

Although a rare diagnosis in the Emergency Department, hypothermia affects patients in all environments, from urban to mountainous settings. Classic signs of death cannot be interpreted in the hypothermic patient, thus resulting in the mantra, "No one is dead until they're warm and dead." This comprehensive review of environmental hypothermia covers the clinical significance and pathophysiology of hypothermia, pearls and pitfalls in the prehospital management of hypothermia (including temperature measurement techniques and advanced cardiac life support deviations), necessary Emergency Department diagnostics, available rewarming modalities including extracorporeal life support, and criteria for termination of resuscitation.

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.

Effect of a vapor barrier in combination with active external rewarming for cold-stressed patients in a prehospital setting: a randomized, crossover field study.

BACKGROUND: Use of a vapor barrier in the prehospital care of cold-stressed or hypothermic patients aims to reduce evaporative heat loss and accelerate rewarming. The application of a vapor barrier is recommended in various guidelines, along with both insulating and wind/waterproof layers and an active external rewarming device; however, evidence of its effect is limited. This study aimed to investigate the effect of using a vapor barrier as the inner layer in the recommended "burrito" model for wrapping hypothermic patients in the field. METHODS: In this, randomized, crossover field study, 16 healthy volunteers wearing wet clothing were subjected to a 30-minute cooling period in a snow chamber before being wrapped in a model including an active heating source either with (intervention) or without (control) a vapor barrier. The mean skin temperature, core temperature, and humidity in the model were measured, and the shivering intensity and thermal comfort were assessed using a subjective questionnaire. The mean skin temperature was the primary outcome, whereas humidity and thermal comfort were the secondary outcomes. Primary outcome data were analyzed using analysis of covariance (ANCOVA). RESULTS: We found a higher mean skin temperature in the intervention group than in the control group after approximately 25 min (p < 0.05), and this difference persisted for the rest of the 60-minute study period. The largest difference in mean skin temperature was 0.93 °C after 60 min. Humidity levels outside the vapor barrier were significantly higher in the control group than in the intervention group after 5 min. There were no significant differences in subjective comfort. However, there was a consistent trend toward increased comfort in the intervention group compared with the control group. CONCLUSIONS: The use of a vapor barrier as the innermost layer in combination with an active external heat source leads to higher mean skin rewarming rates in patients wearing wet clothing who are at risk of accidental hypothermia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05779722.

Frostbite in the Pediatric Population: A Comprehensive Review and a Prospective Canadian Survey.

INTRODUCTION: Frostbite in the pediatric population, where skeletal maturity has not been achieved, can have important repercussions on subsequent growth. Yet, the optimal management of frostbite injuries in children remains vague. This review aims to summarize the current evidence for frostbite management in children and understand Canadian practice trends on this topic. METHODS: A review using Medline, Scopus, Web of Science, and gray literature was performed to identify relevant literature on the clinical manifestations, diagnostic methods, and treatment options in pediatric frostbite. An online survey was sent to plastic surgeons through the Canadian Society of Plastic Surgeons (CSPS) mailing list to further identify national practices and trends for pediatric frostbite management. RESULTS: A total of 109 articles were reviewed. No article provided a specific algorithm for pediatric frostbite, with existing recommendations suggesting the use of adult guidelines for treating children. Our survey yielded 9 responses and highlighted the rarity of pediatric frostbite cases, with no responder treating more than 10 cases per year. Most (55.6%) do not use a pediatric-specific treatment algorithm, whereas 30% apply adult guidelines. A conservative approach focusing on rewarming (55.6%), limb elevation (50%), and tetanus status verification (66.7%) was predominant. Imaging and surgical interventions seem to be reserved for severe cases. CONCLUSIONS: The current literature for pediatric frostbite management lacks specificity. Canadian practices vary, with a trend toward a conservative approach. The limited evidence and rarity of experience highlight the need for further research, ideally in a collaborative multicentric manner, to create a consensus for pediatric frostbite care.

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.

Analysis of rebound intracranial pressure occurring during rewarming after therapeutic hypothermia in traumatic brain injury patients.

OBJECTIVE: To investigate the risk factors associated with rebound intracranial pressure (ICP), a phenomenon that occurs when brain swelling reprogresses rapidly during rewarming in patients who have undergone therapeutic hypothermia for traumatic brain injury (TBI). METHODS: This study analyzed 42 patients who underwent therapeutic hypothermia among 172 patients with severe TBI admitted to a single regional trauma center between January 2017 and December 2020. Forty-two patients were classified into 34.5 °C (mild) and 33 °C (moderate) hypothermia groups according to the therapeutic hypothermia protocol for TBI. Rewarming was initiated post-hypothermia, wherein ICP was maintained at ≤ 20 mmHg and cerebral perfusion pressure was maintained at ≥ 50 mmHg for ≥ 24 h. In the rewarming protocol, the target core temperature was increased to 36.5 °C at 0.1 °C/h. RESULTS: Of the 42 patients who underwent therapeutic hypothermia, 27 did not survive: 9 in the mild and 18 in the moderate hypothermia groups. The moderate hypothermia group had a significantly higher mortality rate than the mild hypothermia group (p = 0.013). Rebound ICP occurred in 9 of 25 patients: 2 in the mild and 7 in the moderate hypothermia groups. In the risk factor analysis of rebound ICP, only the degree of hypothermia was statistically significant, and rebound ICP was observed more frequently in the moderate than in the mild hypothermia group (p = 0.025). CONCLUSIONS: In patients who underwent rewarming after therapeutic hypothermia, rebound ICP presented a higher risk at 33 °C than at 34.5 °C. Therefore, more careful rewarming is needed in patients receiving therapeutic hypothermia at 33 °C.

Rewarming Young Children After Drowning-Associated Hypothermia and Out-of-Hospital Cardiac Arrest: Analysis Using the CAse REport Guideline.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is recommended in adults with drowning-associated hypothermia and out-of-hospital cardiac arrest (OHCA). Our experience of managing a drowned 2-year-old girl with hypothermia (23°C) and cardiac arrest (58 min) prompted this summary using the CAse REport (CARE) guideline to address the question of optimal rewarming procedure in such patients. DESIGN/PATIENTS: Following the CARE guideline, we identified 24 reports in the "PubMed database" describing children less than or equal to 6 years old with a temperature less than or equal to 28°C who had been rewarmed using conventional intensive care ± ECMO. Adding our patient, we were able to analyze a total of 57 cases. MAIN RESULTS: The two groups (ECMO vs non-ECMO) differed with respect to submersion time, pH and potassium but not age, temperature or duration of cardiac arrest. However, 44 of 44 in the ECMO group were pulseless on arrival versus eight of 13 in the non-ECMO group. Regarding survival, 12 of 13 children (92%) undergoing conventional rewarming survived compared with 18 of 44 children (41%) undergoing ECMO. Among survivors, 11 of 12 children (91%) in the conventional group and 14 of 18 (77%) in the ECMO group had favorable outcome. We failed to identify any correlation between "rewarming rate" and "outcome." CONCLUSIONS: In this summary analysis, we conclude that conventional therapy should be initiated for drowned children with OHCA. However, if this therapy does not result in return of spontaneous circulation, a discussion of withdrawal of intensive care might be prudent when core temperature has reached 34°C. We suggest further work is needed using an international registry.

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.

Temperature Control After Cardiac Arrest: A Narrative Review.

Cardiac arrest (CA) is a critical public health issue affecting more than half a million Americans annually. The main determinant of outcome post-CA is hypoxic-ischemic brain injury (HIBI), and temperature control is currently the only evidence-based, guideline-recommended intervention targeting secondary brain injury. Temperature control is a key component of a post-CA care bundle; however, conflicting evidence challenges its wide implementation across the vastly heterogeneous population of CA survivors. Here, we critically appraise the available literature on temperature control in HIBI, detail how the evidence has been integrated into clinical practice, and highlight the complications associated with its use and the timing of neuroprognostication after CA. Future clinical trials evaluating different temperature targets, rates of rewarming, duration of cooling, and identifying which patient phenotype benefits from different temperature control methods are needed to address these prevailing knowledge gaps.

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.

Extracorporeal membrane oxygenation versus conventional rewarming for severe hypothermia in an urban emergency department.

BACKGROUND: Severe hypothermia (core body temperature < 28°C) is life-threatening and predisposes to cardiac arrest. The comparative effectiveness of different active internal rewarming methods in an urban U.S. population is unknown. We aim to compare outcomes between hypothermic emergency department (ED) patients rewarmed conventionally using an intravascular rewarming catheter or warm fluid lavage versus those rewarmed using extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective cohort analysis of adults with severe hypothermia due to outdoor exposure presenting to an urban ED in Minnesota, 2007-2021. The primary outcome was hospital survival. We also calculated the rewarming rate in the 4 h after ED arrival and compared these data between patients rewarmed with ECMO (the extracorporeal rewarming group) versus without ECMO (the conventional rewarming group). We repeated these analyses in the subgroup of patients with cardiac arrest. RESULTS: We analyzed 44 hypothermic ED patients: 25 patients in the extracorporeal rewarming group (median temperature 24.1°C, 84% with cardiac arrest) and 19 patients in the conventional rewarming group (median temperature 26.3°C, 37% with cardiac arrest; 89% received an intravascular rewarming catheter). The median rewarming rate was greater in the extracorporeal versus conventional group (2.3°C/h vs. 1.5°C/h, absolute difference 0.8°C/h, 95% confidence interval [CI] 0.3-1.2°C/h) yet hospital survival was similar (68% vs. 74%). Among patients with cardiac arrest, hospital survival was greater in the extracorporeal versus conventional group (71% vs. 29%, absolute difference 42%, 95% CI 4%-82%). CONCLUSIONS: Among ED patients with severe hypothermia and cardiac arrest, survival was significantly higher with ECMO versus conventional rewarming. Among all hypothermic patients, ECMO use was associated with faster rewarming than conventional methods.

Water Rewarming After Seawater Hypothermia Mitigates IL-1ß in Both Intestinal Tissue and Blood.

In this study, the rat models of severe hypothermia induced by seawater immersion were established in artificial seawater immersion at 15°C for 5 hours. With the rewarming measurement of 37°C water bath, the rewarming effects were evaluated by monitoring basic vital signs and dynamically detecting intestinal inflammation cytokines. Fifty Sprague-Dawley rats were randomly divided into five groups including the control group (group C), hypothermia group (group H), 2-hour rewarming group (group R2), 6-hour rewarming group (group R6), and 12-hour rewarming group (group R12), with 10 in each group. The basic vital signs of rats (i.e., core temperature, respiration, heart rate, and muscle tremor) were constantly recorded. The inflammatory factors were detected in the intestinal tissue via a protein chip GSR-CAA-67 of Innopsys, and the verification by reverse transcription-quantitative polymerase chain reaction. The levels of cytokines (interleukin IL-1ß, IL-6, and IL-10) were detected from blood samples collected at the end of the observation period via enzyme-linked immunosorbent assay. The expression landscape of IL-1ß in the intestinal tissue was validated by immunohistochemistry. Five hours of immersion in artificial seawater at 15°C successfully induced severe hypothermia of rats. After 2 hours of constant water bath rewarming at 37°C, the basic vital signs recovered to the normal level and maintained stably as well as the acute inflammatory reaction alleviated effectively, which indicated that 37°C of water immersion rewarming had the potential to be a suitable method for early treatment of water immersion hypothermia. After the process of hypothermia, several inflammatory cytokines of rats in rewarming groups changed distinctly with IL-1ß, showing the most significant variations compared with group C, which confirmed IL-1ß as a potential monitoring biomarker referring to the therapeutic effect of rewarming for severe hypothermia caused by seawater immersion.

Prolonged Controlled Oxygenated Rewarming Improves Immediate Tubular Function and Energetic Recovery of Porcine Kidneys During Normothermic Machine Perfusion.

BACKGROUND: Normothermic machine perfusion (NMP) is typically performed after a period of hypothermic preservation, which exposes the kidney to an abrupt increase in temperature and intravascular pressure. The resultant rewarming injury could be alleviated by gradual rewarming using controlled oxygenated rewarming (COR). This study aimed to establish which rewarming rate during COR results in the best protective effect on renal rewarming injury during subsequent NMP. METHODS: Twenty-eight viable porcine kidneys (n = 7/group) were obtained from a slaughterhouse. After these kidneys had sustained 30 min of warm ischemia and 24 h of oxygenated HMP, they were either rewarmed abruptly from 4-8 °C to 37 °C by directly initiating NMP or gradually throughout 30, 60, or 120 min of COR (rate of increase in kidney temperature of 4.46%/min, 2.20%/min, or 1.10%/min) before NMP. RESULTS: Kidneys that were rewarmed during the course of 120 min (COR-120) had significantly lower fractional excretion of sodium and glucose at the start of NMP compared with rewarming durations of 30 min (COR-30) and 60 min (COR-60). Although COR-120 kidneys showed superior immediate tubular function at the start of normothermic perfusion, this difference disappeared during NMP. Furthermore, energetic recovery was significantly improved in COR-30 and COR-120 kidneys compared with abruptly rewarmed and COR-60 kidneys. CONCLUSIONS: This study suggests that a rewarming rate of 1.10%/min during COR-120 could result in superior immediate tubular function and energetic recovery during NMP. Therefore, it may provide the best protective effect against rewarming injury.