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Background: The prognostic value of body temperature in sepsis-induced coagulopathy (SIC) remains unclear. In this study we aimed to investigate the association between temperature and mortality among SIC patients.Methods: We analyzed data for 9,860 SIC patients from an intensive care database. Patients were categorized by maximum temperature in the first 24 hours into the following: ≤36.0°C; 36.0–37.0°C; 37.0–38.0°C; 38.0–39.0°C; and ≥39.0°C. The primary outcome was 28-day mortality. We used multivariate regression to analyze the temperature-mortality association.Results: The 37.0–38.0°C, 38.0–39.0°C and ≥39.0°C groups correlated with lower 28-day mortality (adjusted HR 0.70, 0.76 and 0.72, respectively), while the

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Acute limb ischaemia (ALI) is an emergent clinical condition that strains pre-hospital resources and impacts healthcare costs and patient quality of life. Hypothermia has long been used in clinical and research settings to mitigate ischaemic damage in tissues, but prompt reperfusion is needed to prevent loss of limb or function from ALI. To address the unmet need for pre-hospital intervention of threatened limbs awaiting definitive specialty care, we have focused on controlled application of hypothermia. Over years of animal experiments, phantom limb creation, and materials selection, we conceptualised and created a portable limb-cooling device that can be used alone or combined with a traditional tourniquet or resuscitative endovascular balloon occlusion of the aorta. Here, we describe our process of building and testing the device, from computer simulation through animal-limb metabolic studies, to prototype testing.

OBJECTIVE: To study the association between the Sarnat exam (SE) performed before and after therapeutic hypothermia (TH) and outcomes at 2 years in infants with moderate or severe hypoxic-ischaemic encephalopathy (HIE). DESIGN: Secondary analysis of the High-dose Erythropoietin for Asphyxia and EncephaLopathy Trial. Adjusted ORs (aORs) for death or neurodevelopmental impairment (NDI) based on SE severity category and change in category were constructed, adjusting for sedation at time of exam. Absolute SE Score and its change were compared for association with risk for death or NDI using locally estimated scatterplot smoothing curves. SETTING: Randomised, double-blinded, placebo-controlled multicentre trial including 17 centres across the USA. PATIENTS: 479/500 enrolled neonates who had both a qualifying SE (qSE) before TH and a SE after rewarming (rSE). INTERVENTIONS: Standardised SE was used across sites before and after TH. All providers underwent standardised SE training. MAIN OUTCOME MEASURES: Primary outcome was defined as the composite outcome of death or any NDI at 22-36 months. RESULTS: Both qSE and rSE were associated with the primary outcome. Notably, an aOR for primary outcome of 6.2 (95% CI 3.1 to 12.6) and 50.3 (95% CI 13.3 to 190) was seen in those with moderate and severe encephalopathy on rSE, respectively. Persistent or worsened severity on rSE was associated with higher odds for primary outcome compared with those who improved, even when qSE was severe. CONCLUSION: Both rSE and change between qSE and rSE were strongly associated with the odds of death/NDI at 22-36 months in infants with moderate or severe HIE.

BackgroundInfants with hypoxic-ischemic encephalopathy are often treated with therapeutic hypothermia and high-frequency ventilation. Fluctuations in PaCO2 during therapeutic hypothermia are associated with poor neurodevelopmental outcomes. Transcutaneous CO2 monitors offer a noninvasive estimate of PaCO2 represented by transcutaneously measured partial pressure of carbon dioxide (PtcCO2 ). We aimed to assess the precision between PtcCO2 and PaCO2 values in neonates undergoing therapeutic hypothermia.MethodsThis was a retrospective chart review of 10 neonates who underwent therapeutic hypothermia requiring respiratory support over 2 y. A range of 2-27 simultaneous PtcCO2 and PaCO2 pairs of measurements per neonate were analyzed via linear mixed models and a Bland-Altman plot for multiple observations per neonate.ResultsA linear mixed-effect model demonstrated that PtcCO2 and PaCO2 (controlling for sex) were similar. The 95% CI of the mean difference ranged from -2.3 to 5.7 mm Hg (P = .41). However, precision was poor as the PtcCO2 ranged from > 18 mm Hg to < 13 mm Hg than PaCO2 values for 95% of observations.ConclusionsThe neonates' PtcCO2 was as much as 18 mm Hg higher to 13 mm Hg lower than the PaCO2 95% of the time. Transcutaneous CO2 monitoring may not be a good trending tool, nor is it appropriate for estimating PaCO2 in patients undergoing therapeutic hypothermia.

No preclinical experimental approach enables the study of voluntary oral consumption of high-concentration Δ9-tetrahydrocannabinol (THC) and its intoxicating effects, mainly owing to the aversive response of rodents to THC that limits intake. Here, we developed a palatable THC formulation and an optimized access paradigm in mice to drive voluntary consumption. THC was formulated in chocolate gelatin (THC-E-gel). Adult male and female mice were allowed ad libitum access for 1 and 2 hr. Cannabimimetic responses (hypolocomotion, analgesia, and hypothermia) were measured following access. Levels of THC and its metabolites were measured in blood and brain tissue. Acute acoustic startle responses were measured to investigate THC-induced psychotomimetic behavior. When allowed access for 2 hr to THC-E-gel on the second day of a 3-day exposure paradigm, adult mice consumed up to ≈30 mg/kg over 2 hr, which resulted in robust cannabimimetic behavioral responses (hypolocomotion, analgesia, and hypothermia). Consumption of the same gelatin decreased on the following third day of exposure. Pharmacokinetic analysis shows that THC-E-gel consumption led to parallel accumulation of THC and its psychoactive metabolite, 11-OH-THC, in the brain, a profile that contrasts with the known rapid decline in brain 11-OH-THC levels following THC intraperitoneal (i.p.) injections. THC-E-gel consumption increased the acoustic startle response in males but not in females, demonstrating a sex-dependent effect of consumption. Thus, while voluntary consumption of THC-E-gel triggered equivalent cannabimimetic responses in male and female mice, it potentiated acoustic startle responses preferentially in males. We built a dose-prediction model that included cannabimimetic behavioral responses elicited by i.p. versus THC-E-gel to test the accuracy and generalizability of this experimental approach and found that it closely predicted the measured acoustic startle results in males and females. In summary, THC-E-gel offers a robust preclinical experimental approach to study cannabimimetic responses triggered by voluntary consumption in mice, including sex-dependent psychotomimetic responses.

Introduction The association between hypothermia, coagulopathy, and acidosis in trauma is well described. Hypothermia mitigation starts in the prehospital setting; however, it is often a secondary focus after other life-saving interventions. The deployed environment further compounds the problem due to prolonged evacuation times in rotary wing aircraft, resource limitations, and competing priorities. This analysis evaluates hypothermia in combat casualties and the relationship to resuscitation strategy with blood products. Methods Using the data from the Department of Defense Joint Trauma Registry from 2003 to 2021, a retrospective analysis was conducted on adult trauma patients. Inclusion criteria was arrival at the first military treatment facility (MTF) hypothermic (<95ºF). Study variables included: mortality, year, demographics, battle vs non-battle injury, mechanism, theater of operation, vitals, and labs. Subgroup analysis was performed on severely injured (15 < ISS < 75) hypothermic trauma patients resuscitated with whole blood (WB) vs only component therapy. Results Of the 69,364 patients included, 908 (1.3%) arrived hypothermic; the vast majority of whom (N  = 847, 93.3%) arrived mildly hypothermic (90–94.9°F). Overall mortality rate was 14.8%. Rates of hypothermia varied by year from 0.7% in 2003 to 3.9% in 2014 (P <0.005). On subgroup analysis, mortality rates were similar between patients resuscitated with WB vs only component therapy; though base deficit values were higher in the WB cohort (−10 vs −6, P  < 0.001). Conclusion Despite nearly 20 years of combat operations, hypothermia continues to be a challenge in military trauma and is associated with a high mortality rate. Mortality was similar between hypothermic trauma patients resuscitated with WB vs component therapy, despite greater physiologic derangements on arrival in patients who received WB. As the military has the potential to conduct missions in environments where the risk of hypothermia is high, further research into hypothermia mitigation techniques and resuscitation strategies in the deployed setting is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neonatal hypothermia is a common and preventable cause of neonatal morbidity and mortality. Although hypothermia prevention has been extensively studied in infants <32 weeks' gestation, the authors of few studies have targeted moderate- and late-preterm infants (MLPIs) in the delivery room. METHODS: This quality improvement initiative was conducted from June 2019 to June 2023 at the Massachusetts General Hospital NICU and Labor and Delivery Unit. All inborn MLPIs 32 1 0/7 to 36 1 6/7 weeks' gestation admitted to the NICU were included. We expanded thermoregulatory measures typically used in protocols for infants <32 weeks' gestation, including increasing delivery room ambient temperature to 74° F and thermal mattress use. The primary outcome was hypothermia (<36.5°C) after NICU admission. The balancing measure was hyperthermia (≥38 °C). RESULTS: During the study period, there were 566 inborn MLPIs with a mean gestational age of 34 1 3/7 weeks and a mean birth weight of 2269 g. Special cause variation in neonatal hypothermia incidence was observed with a decrease from a mean baseline of 27% to 7.8% postintervention. Special cause variation was observed in hyperthermia incidence, with an increase from 1.4% to 6.2% postintervention largely initially associated with noncompliance with the protocol for thermal mattress removal. CONCLUSIONS: The expansion of several thermoregulation techniques commonly used in infants <32 weeks' gestation, particularly thermal mattress use, was associated with a decreased incidence of NICU admission hypothermia in MLPIs, with an increase in mild hyperthermia predominantly associated with concomitant polyethylene wrap use. [ABSTRACT FROM AUTHOR]

Introduction Hypothermia increases mortality in trauma populations and frequently occurs in military casualties due to the nature of combat environments. The association between hypothermia and the time of year when injured remains unclear. We sought to determine the association between seasonal changes in temperature and hypothermia among combat casualties. Materials and Methods This observational study was a secondary analysis of a previously described Department of Defense Trauma Registry dataset which included U.S. military and Coalition casualties who received prehospital care from January 2007 to March 2020 in Afghanistan and Iraq. We tested for associations between hypothermia (<36.2°C) and seasonal ambient temperatures by constructing multivariable logistic regression models. Summer was defined as June through August and winter as December through February. We assumed that the combat operations occurred in the area near the point of first contact with the deployed military treatment facilities. This study was determined to be exempt from Institutional Review Board oversight. Results There were 5,821 that met inclusion for this study. Within the multivariable logistic regression model, we adjusted for injury severity score, mechanism of injury, and imputed transport time, finding that combat casualties were 2.28 (odds ratio, 95% confidence interval 1.93-2.69) times more likely to develop hypothermia in the winter versus summer. When using temperature as a continuous outcome, casualties had a lower emergency department temperature during the winter (parameter estimate −0.133°C, P  < 0.001) after adjusting for confounders. In casualties experiencing hypothermia, mortality was higher (4% versus 1%, P  < 0.001), and composite median injury severity score values were higher (10 versus 5, P  < 0.001). Among hypothermic casualties, serious injuries were significantly more common (all P  < 0.001) to the head (15% versus 7%), thorax (15% versus 7%), abdomen (9% versus 6%), extremities (35% versus 22%), and skin (4% versus 2%). Conclusions We found a seasonal variation in the occurrence of hypothermia in a large cohort of trauma casualties. Despite adjustment for multiple known confounders, our findings substantiate probable ambient temperature variations to trauma-induced hypothermia. Furthermore, our findings, when taken in the context of other studies on the efficacy of current hypothermia prevention and treatment strategies, support the need for better methods to mitigate hypothermia in future cold-weather operations. [ABSTRACT FROM AUTHOR]

This trial was carried out to investigate the effect of forced air warming in various body areas of women on hypothermia during cesarean delivery. The patients in the study groups (n = 76) were assigned to the full-body warming group, upper-extremity warming group, lower-extremity warming group, and control groups. The intervention groups received forced-air warming 30 min before the surgery and continued until 30 min after surgery. The incidence of hypothermia was significantly higher in the control group than in the other groups at the 60th minute of the operation (p < 0.01). The intervention and control groups showed significant differences in the frequency of shivering at the entrance to the PACU (p = 0.001). Thermal comfort scores have significant difference between the control group and all of the intervention groups (p<.001). It is said that the full-body forced-air warming technique prevents hypothermia, shivering, and thermal discomfort in women Cesarean Section (CS). [ABSTRACT FROM AUTHOR]

Intravenous alpha-2-adrenergic receptor agonists reduce energy expenditure and lower the temperature when shivering begins in humans, allowing a decrease in core body temperature. Because there are few data about similar effects from oral drugs, we tested whether single oral doses of the sedative dexmedetomidine (1 µg/kg sublingual or 4 µg/kg swallowed) or the muscle relaxant tizanidine (8 mg or 16 mg), combined with surface cooling, reduce energy expenditure and core body temperature in humans. A total of 26 healthy participants completed 41 one-day laboratory studies measuring core body temperature using an ingested telemetry capsule and measuring energy expenditure using indirect calorimetry for up to 6 hours after drug ingestion. Dexmedetomidine induced a median 13% – 19% peak reduction and tizanidine induced a median 15% – 22% peak reduction in energy expenditure relative to baseline. Core body temperature decreased a median of 0.5°C – 0.6°C and 0.5°C – 0.7°C respectively. Decreases in temperature occurred after peak reductions in energy expenditure. Energy expenditure increased with a decrease in core temperature in control participants but did not occur after 4 µg/kg dexmedetomidine or 16 mg tizanidine. Plasma levels of dexmedetomidine but not tizanidine were related to mean temperature change. Decreases in heart rate, blood pressure, respiratory rate, cardiac stroke volume index, and cardiac index were associated with the change in metabolic rate after higher drug doses. We conclude that both oral dexmedetomidine and oral tizanidine reduce energy expenditure and allow decrease in core temperature in humans. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) remains a significant challenge in critical care, with high mortality rates despite advancements in treatment. Venovenous extracorporeal membrane oxygenation (VV-ECMO) is employed as salvage therapy for refractory cases. However, some patients may continue to experience persistent severe hypoxemia despite being treated with VV-ECMO. To achieve this, moderate hypothermia and short-acting selective β1-blockers have been proposed. Methods: Using a swine model of severe ARDS treated with VV-ECMO, this study investigated the efficacy of moderate hypothermia or β-blockade in improving arterial oxygen saturation (SaO2) three hours after VV-ECMO initiation. Primary endpoints included the ratio of VV-ECMO flow to cardiac output and arterial oxygen saturation before VV-ECMO start (H0) and three hours after ECMO start (H3). Secondary safety criteria encompassed hemodynamics and oxygenation parameters. Results: Twenty-two male pigs were randomized into three groups: control (n = 6), hypothermia (n = 9) and β-blockade (n = 7). At H0, all groups demonstrated similar hemodynamic and respiratory parameters. Both moderate hypothermia and β-blockade groups exhibited a significant increase in the ratio of VV-ECMO flow to cardiac output at H3, resulting in improved SaO2. At H3, despite a decrease in oxygen delivery and consumption in the intervention groups compared to the control group, oxygen extraction ratios across groups remained unchanged and lactate levels were normal. Conclusions: In a swine model of severe ARDS treated with VV-ECMO, both moderate hypothermia and β-blockade led to an increase in the ratio of VV-ECMO flow to cardiac output resulting in improved arterial oxygen saturation without any impact on tissue perfusion. [ABSTRACT FROM AUTHOR]