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.

Decreasing incidence of admission neonatal hypothermia in Gandhi Memorial Hospital, Addis Ababa, Ethiopia: quality improvement project.

BACKGROUND: WHO reported that neonatal hypothermia accounts for about 27% of newborn deaths worldwide. It is a serious concern in Ethiopia and other parts of sub-Saharan Africa; it poses a serious threat to global health, increasing morbidity and mortality. Hypothermic neonates are more likely to experience respiratory distress, infections and other issues that could result in longer hospital stays and delayed development. The objective of this quality improvement project was to minimise intensive medical treatments, maximise resource usage and enhance overall health outcomes for newborns at Gandhi Memorial Hospital by reducing neonatal hypothermia. METHODS: Over 10 months (from 1 March 2021 to 30 January 2022), neonatal hypothermia incidence was assessed using Quality Supervision Mentoring Team and Health Management Information System data. Root cause analysis and literature review led to evidence-based interventions in a change bundle. After team training and neonatal intensive care unit (NICU) relocation, Plan-Do-Study-Act cycles tested the bundle. Close temperature monitoring and data collection occurred. Run charts evaluated intervention success against baseline data, informing conclusions about effectiveness. RESULT: The quality improvement project reduced neonatal hypothermia in NICU admissions from a baseline median of 80.6% to a performance median of 30%. CONCLUSION AND RECOMMENDATION: The quality improvement project at Gandhi Memorial Hospital effectively reduced neonatal hypothermia through interventions such as the temperature management bundle and NICU relocation, leading to improved patient care, fewer hypothermic neonates and enhanced body temperature management. Continuous monitoring, adherence to best practices, sharing success and outcome assessment are crucial for enhancing the project's effectiveness and sustaining positive impacts on neonatal hypothermia reduction and patient outcomes.

Changes in temperature in preheated crystalloids at ambient temperatures relevant to a prehospital setting: an experimental simulation study with the application of prehospital treatment of trauma patients suffering from accidental hypothermia.

BACKGROUND: Accidental hypothermia is common in all trauma patients and contributes to the lethal diamond, increasing both morbidity and mortality. In hypotensive shock, fluid resuscitation is recommended using fluids with a temperature of 37-42°, as fluid temperature can decrease the patient's body temperature. In Sweden, virtually all prehospital services use preheated fluids. The aim of the present study was to investigate how the temperature of preheated infusion fluids is affected by the ambient temperatures and flow rates relevant for prehospital emergency care. METHODS: In this experimental simulation study, temperature changes in crystalloids preheated to 39 °C were evaluated. The fluid temperature changes were measured both in the infusion bag and at the patient end of the infusion system. Measurements were conducted in conditions relevant to prehospital emergency care, with ambient temperatures varying between - 4 and 28 °C and flow rates of 1000 ml/h and 6000 ml/h, through an uninsulated infusion set at a length of 175 cm. RESULTS: The flow rate and ambient temperature affected the temperature in the infusion fluid both in the infusion bag and at the patient end of the system. A lower ambient temperature and lower flow rate were both associated with a greater temperature loss in the infusion fluid. CONCLUSION: This study shows that both a high infusion rate and a high ambient temperature are needed if an infusion fluid preheated to 39 °C is to remain above 37 °C when it reaches the patient using a 175-cm-long uninsulated infusion set. It is apparent that the lower the ambient temperature, the higher the flow rate needs to be to limit temperature loss of the fluid.

Inequalities in birth before arrival at hospital in South West England: a multimethods study of neonatal hypothermia and emergency medical services call-handler advice.

OBJECTIVES: To examine inequalities in birth before arrival (BBA) at hospitals in South West England, understand which groups are most likely to experience BBA and how this relates to hypothermia and outcomes (phase A). To investigate opportunities to improve temperature management advice given by emergency medical services (EMS) call-handlers during emergency calls regarding BBA in the UK (phase B). DESIGN: A two-phase multimethod study. Phase A analysed anonymised data from hospital neonatal records between January 2018 and January 2021. Phase B analysed anonymised EMS call transcripts, followed by focus groups with National Health Service (NHS) staff and patients. SETTING: Six Hospital Trusts in South West England and two EMS providers (ambulance services) in South West and North East England. PARTICIPANTS: 18 multidisciplinary NHS staff and 22 members of the public who had experienced BBA in the UK. RESULTS: 35% (64/184) of babies conveyed to hospital were hypothermic on arrival. When compared with national data on all births in the South West, we found higher percentages of women with documented safeguarding concerns at booking, previous live births and 'late bookers' (booking their pregnancy >13 weeks gestation). These women may, therefore, be more likely to experience BBA. Preterm babies, babies to first-time mothers and babies born to mothers with disability or safeguarding concerns at booking were more likely to be hypothermic following BBA. Five main themes emerged from qualitative data on call-handler advice: (1) importance placed on neonatal temperature; (2) advice on where the baby should be placed following birth; (3) advice on how to keep the baby warm; (4) timing of temperature management advice and (5) clarity and priority of instructions. CONCLUSIONS: Findings identified factors associated with BBA and neonatal hypothermia following BBA. Improvements to EMS call-handler advice could reduce the number of babies arriving at hospital hypothermic.

Delayed Rewarming Thrombocytopenia: A Suggested Preventable and Treatable Cause of Rewarming Deaths.

The lack of a consensus of accepted prognostic factors in hypothermia suggests an additional factor has been overlooked. Delayed rewarming thrombocytopenia (DRT) is a novel candidate for such a role. At body temperature, platelets undergoing a first stage of aggregation are capable of progression to a second irreversible stage of aggregation. However, we have shown that the second stage of aggregation does not occur below 32°C and that this causes the first stage to become augmented (first-stage platelet hyperaggregation). In aggregometer studies performed below 32°C, the use of quantities of ADP that cause a marked first-stage hyperaggregation can cause an augmented second-stage activation of the platelets during rewarming (second-stage platelet hyperaggregation). In vivo, after 24 hours of hypothermia, platelets on rewarming seem to undergo second-stage hyperaggregation, from ADP released from erythrocytes, leading to life-threatening thrombocytopenia. This hyperaggregation is avoidable if heparin is given before the hypothermia or if aspirin, alcohol or platelet transfusion is given during the hypothermia before reaching 32°C on rewarming. Many of the open questions existing in this field are explained by DRT. Prevention and treatment of DRT could be of significant value in preventing rewarming deaths and some cases of rescue collapse. Performing platelet counts during rewarming will demonstrate potentially fatal thrombocytopenia and enable treatment with platelet infusions aspirin or alcohol.

Hypothermic Cardiac Arrest: A Case Report of an Unexpected Survivor Using Air Medical Transportation in Nepal.

This is a case of a 34-year-old man surviving hypothermic cardiac arrest with excellent neurologic recovery in Nepal. After 3 days without communication at an altitude of approximately 6,000 m, the patient was located in a crevasse and retrieved by a helicopter-supported search and rescue team. At first contact, he was reported to be breathing and shivering with appropriate pupillary response. The patient was then flown to a local teaching hospital where he was assessed on arrival and found to be in cardiac arrest with absence of spontaneous breathing and a central pulse and bilaterally fixed and dilated pupils. An electrocardiogram demonstrated asystole, and his core temperature was unrecordably low on the available device. After resuscitation and return of spontaneous circulation, the patient received a secondary helicopter transfer to a major hospital in the capital, Kathmandu, where his recovery continued. The report discusses the physiological basis of the relatively favorable outcomes observed in hypothermic cardiac arrest and highlights the operations and capability of helicopter emergency medical services in a country on the United Nations list of least developed nations.

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

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

Predictors of cardiac arrest in severe accidental hypothermia.

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

Therapeutic hypothermia modulates the neurogenic response of the newborn piglet subventricular zone after hypoxia-ischemia.

BACKGROUND: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. To investigate the neurogenic response to hypoxia-ischemia (HI) followed by normothermia (38.5 °C) or three different hypothermic temperatures (35, 33.5, or 30 °C) in the subventricular zone (SVZ) of the neonatal piglet. METHODS: Following transient cerebral HI and resuscitation, 28 newborn piglets were randomized to: normothermia or whole-body cooling to 35 °C, 33.5 °C, or 30 °C during 2-26 h (all n = 7). At 48 h, piglets were euthanized and SVZ obtained to evaluate its cellularity, pattern of cell death, radial glia length, doublecortin (DCX, neuroblasts) expression, and Ki67 (cell proliferation) and Ki67/Sox2 (neural stem/progenitor dividing) cell counts. RESULTS: Normothermic piglets showed lower total (Ki67+) and neural stem/progenitor dividing (Ki67+Sox2+) cell counts when compared to hypothermic groups. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and DCX immunohistochemistry. Cooling to 30 °C, however, revealed decreased cellularity in the lateral SVZ and shorter radial glia processes when compared with 33.5 °C. CONCLUSIONS: In a neonatal piglet model, hypothermia to 33.5 °C modulates the neurogenic response of the SVZ after HI, highlighting the potential beneficial effect of hypothermia to 33.5 °C on endogenous neurogenesis and the detrimental effect of overcooling beyond this threshold. IMPACT: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. Hypothermia may modulate neurogenesis in the subventricular zone (SVZ) of the neonatal hypoxic-ischemic piglet. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and doublecortin immunohistochemistry; cooling to 30 °C, however, revealed decreased cellularity and shorter radial glia processes. In a neonatal piglet model, therapeutic hypothermia (33.5 °C) modulates the neurogenic response of the SVZ after hypoxia-ischemia, highlighting also the detrimental effect of overcooling beyond this threshold.

Metabolic Manipulation and Therapeutic Hypothermia.

Hypothermia has multiple physiological effects, including decreasing metabolic rate and oxygen consumption (VO2). There are few human data about the magnitude of change in VO2 with decreases in core temperature. We aimed to quantify to magnitude of reduction in resting VO2 as we reduced core temperature in lightly sedated healthy individuals. After informed consent and physical screening, we cooled participants by rapidly infusing 20 mL/kg of cold (4°C) saline intravenously and placing surface cooling pads on the torso. We attempted to suppress shivering using a 1 mcg/kg intravenous bolus of dexmedetomidine followed by titrated infusion at 1.0 to 1.5 µg/(kg·h). We measured resting metabolic rate VO2 through indirect calorimetry at baseline (37°C) and at 36°C, 35°C, 34°C, and 33°C. Nine participants had mean age 30 (standard deviation 10) years and 7 (78%) were male. Baseline VO2 was 3.36 mL/(kg·min) (interquartile range 2.98-3.76) mL/(kg·min). VO2 was associated with core temperature and declined with each degree decrease in core temperature, unless shivering occurred. Over the entire range from 37°C to 33°C, median VO2 declined 0.7 mL/(kg·min) (20.8%) in the absence of shivering. The largest average decrease in VO2 per degree Celsius was by 0.46 mL/(kg·min) (13.7%) and occurred between 37°C and 36°C in the absence of shivering. After a participant developed shivering, core body temperature did not decrease further, and VO2 increased. In lightly sedated humans, metabolic rate decreases around 5.2% for each 1°C decrease in core temperature from 37°C to 33°C. Because the largest decrease in metabolic rate occurs between 37°C and 36°C, subclinical shivering or other homeostatic reflexes may be present at lower temperatures.

Impact of accidental hypothermia in trauma patients: A retrospective cohort study.

BACKGROUND: Trauma patients with hypothermia have substantial increases in mortality and morbidity. In severely injured patients, hypothermia is common with a rate up to 50% in various geographic areas. This study aims to elucidate the incidence, predictors, and impact of hypothermia on outcomes in severely injured patients. METHODS: This was a retrospective cohort study which included trauma patients with an Injury Severity Score (ISS) ≥ 16 admitted to a level 1 trauma center in the Netherlands between January 1, 2015 and December 31, 2021. Primary outcome was incidence of hypothermia on arrival at the emergency department. Factors associated with hypothermia were identified. Secondary outcomes were transfusion requirement, mortality, and intensive care unit (ICU) admission. Logistic regression analysis was used to identify associations. RESULTS: A total of 2032 severely injured patients were included of which 257 (12.6%) were hypothermic on hospital arrival. Predictors for hypothermia on hospital arrival included higher ISS, prehospital intubation, cervical spine immobilization, winter months, systolic blood pressure (SBP) < 90 mmHg and Glasgow Coma Scale (GCS) ≤ 8. Hypothermia was independently associated with transfusion requirement (OR, 2.68; 95% CI, 1.94 - 3.73; p < 0.001), mortality (OR, 2.12; 95% CI, 1.40 - 3.19; p < 0.001) and more often ICU admission (OR, 1.81; 95% CI, 1.10 - 2.97, p = 0.019). CONCLUSIONS: In this study, hypothermia was present in 12.6% of severely injured patients. Hypothermia was associated with increased transfusion requirement, mortality, and ICU admission. Identified predictors for hypothermia included the severity of injury, intubation, and immobilization, as well as winter season, SBP < 90 mmHg, and GCS ≤ 8.

Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis. METHODS: The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects. RESULTS: Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14-38.83; however, the overall evidence quality was low for the small sample size. CONCLUSIONS: Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.

Therapeutic Hypothermia in Treating Glioblastoma: A Review.

Glioblastoma (GBM) is the most commonly occurring of all malignant central nervous system (CNS) tumors in adults. Considering the low median survival of only ∼15 months and poor prognosis in GBM patients, despite surgical resection with adjuvant radiation and chemotherapy, it is vital to seek brand new and innovative treatment in combination with already existing methods. Hypothermia participates in many metabolic pathways, inflammatory responses, and apoptotic processes, while also promoting the integrity of neurons. Following the successful application of therapeutic hypothermia across a spectrum of disorders such as traumatic CNS injury, cardiac arrest, and epilepsy, several clinical trials have set to evaluate the potency of hypothermia in treating a variety of cancers, including breast and ovaries cancer. In regard to primary neoplasms and more specifically, GBM, hypothermia has recently shown promising results as an auxiliary treatment, reinforcing chemotherapy's efficacy. In this review, we discuss the recent advances in utilizing hypothermia as treatment for GBM and other cancers.

Rectal temperature after hypoxia-ischemia predicts white matter and cortical pathology in the near-term ferret.

BACKGROUND: Neonatal encephalopathy (NE) remains a common cause of infant morbidity and mortality. Neuropathological corollaries of NE associated with acute hypoxia-ischemia include a central injury pattern involving the basal ganglia and thalamus, which may interfere with thermoregulatory circuits. Spontaneous hypothermia (SH) occurs in both preclinical models and clinical hypoxic-ischemic NE and may provide an early biomarker of injury severity. To determine whether SH predicts the degree of injury in a ferret model of hypoxic-ischemic NE, we investigated whether rectal temperature (RT) 1 h after insult correlated with long-term outcomes. METHODS: Postnatal day (P)17 ferrets were presensitized with Escherichia coli lipopolysaccharide before undergoing hypoxia-ischemia/hyperoxia (HIH): bilateral carotid artery ligation, hypoxia-hyperoxia-hypoxia, and right ligation reversal. One hour later, nesting RTs were measured. RESULTS: Animals exposed to HIH were separated into normothermic (NT; ≥34.4 °C) or spontaneously hypothermic (SH; <34.4 °C) groups. At P42, cortical development, ex vivo MRI, and neuropathology were quantitated. Whole-brain volume and fractional anisotropy in SH brains were significantly decreased compared to control and NT animals. SH brains also had significantly altered gyrification, greater cortical pathology, and increased corpus callosum GFAP staining relative to NT and control brains. CONCLUSION: In near-term-equivalent ferrets, nesting RT 1 h after HIH may predict long-term neuropathological outcomes. IMPACT: High-throughput methods to determine injury severity prior to treatment in animal studies of neonatal brain injury are lacking. In a gyrified animal model of neonatal inflammation-sensitized hypoxic-ischemic brain injury in the ferret, rectal temperature 1 h after hypoxia predicts animals who will have increased cortical pathology and white matter changes on MRI. These changes parallel similar responses in rodents and humans but have not previously been correlated with long-term neuropathological outcomes in gyrified animal models. Endogenous thermoregulatory responses to injury may provide a translational marker of injury severity to help stratify animals to treatment groups or predict outcome in preclinical studies.