Explore the vast range of titles available.

In this trial involving patients after out-of-hospital cardiac arrest, fever prevention for 36 or 72 hours did not result in different percentages of patients dying or having severe disability or coma.

In this study of three strategies — hypothermia, machine perfusion, or both — for pretransplantation preservation of kidneys from brain-dead donors, hypothermia was found to be inferior to machine perfusion.

Background Impaired oxygen delivery or blood flow to the brain around the time of birth can cause injury. Hypoxic ischaemic encephalopathy (HIE) is a leading cause of death and disability in term and near-term infants. Therapeutic hypothermia (TH) (reducing body temperature to 33–34 °C for 72 h after birth) is the only intervention available for infants with moderate-to-severe encephalopathy. TH should be initiated within 6 h of birth for maximum benefit. Many infants worldwide are not born in a centre where TH is possible, and transport is required for active TH. In Australia, the current method of active TH during transport involves ice-gel packs. There have been no prospective studies comparing active methods of TH in neonatal transport reporting short- and long-term outcomes. We aim to compare two active TH modalities: a battery servo-controlled cooling device and infant wrap (Criticool Mini and Cruewrap (Belmont Medical Technologies, MA, USA)) and standard care (ice-gel packs) for TH during the transport of newborns with HIE. Methods The CoolCot study will be conducted in the Newborn Emergency Transport Service of Western Australia (NETS WA), a single state-wide transport service. Eligible infants with confirmed or suspected HIE will be referred to NETS WA from healthcare facilities without tertiary health (TH) capacity in Western Australia. Following the arrival of the transport team, infants with informed consent will be randomly assigned to battery-enabled servo-controlled TH or standard care (ice-gel packs). The primary outcome will be the proportion of patients with a temperature in the range of 33.0–34.0 °C on arrival at the receiving unit. The secondary outcomes include the time to achieve the therapeutic temperature, the time spent out of the temperature range, the degree of temperature fluctuation and safety. Long-term measures: MRI brain findings (days 5–10 of life) and Bayley Scales of Infant Development assessment at 2 years. Discussion The CoolCot study is the first RCT to prospectively compare the effectiveness of active cooling methods in neonatal emergency transport. Reducing the time needed to achieve the target temperature is crucial in optimising neurodevelopmental outcomes. A key feature of this study is the neurodevelopmental assessment conducted at age two. Trial registration WHO ICTRP Registry/Australian New Zealand Clinical Trials Registry: ACTRN12623001298606p. The CoolCot trial was prospectively registered on 13th December 2023.

Moderate intraoperative hypothermia promotes myocardial injury, surgical site infections, and blood loss. Whether aggressive warming to a truly normothermic temperature near 37°C improves outcomes remains unknown. We aimed to test the hypothesis that aggressive intraoperative warming reduces major perioperative complications. In this multicentre, parallel group, superiority trial, patients at 12 sites in China and at the Cleveland Clinic in the USA were randomly assigned (1:1) to receive either aggressive warming to a target core temperature of 37°C (aggressively warmed group) or routine thermal management to a target of 35·5°C (routine thermal management group) during non-cardiac surgery. Randomisation was stratified by site, with computer-generated, randomly sized blocks. Eligible patients (aged ≥45 years) had at least one cardiovascular risk factor, were scheduled for inpatient non-cardiac surgery expected to last 2–6 h with general anaesthesia, and were expected to have at least half of the anterior skin surface available for warming. Patients requiring dialysis and those with a body-mass index exceeding 30 kg/m2 were excluded. The primary outcome was a composite of myocardial injury (troponin elevation, apparently of ischaemic origin), non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery, as assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03111875. Between March 27, 2017, and March 16, 2021, 5056 participants were enrolled, of whom 5013 were included in the intention-to-treat population (2507 in the aggressively warmed group and 2506 in the routine thermal management group). Patients assigned to aggressive warming had a mean final intraoperative core temperature of 37·1°C (SD 0·3) whereas the routine thermal management group averaged 35·6°C (SD 0·3). At least one of the primary outcome components (myocardial injury after non-cardiac surgery, cardiac arrest, or mortality) occurred in 246 (9·9%) of 2497 patients in the aggressively warmed group and in 239 (9·6%) of 2490 patients in the routine thermal management group. The common effect relative risk of aggressive versus routine thermal management was an estimated 1·04 (95% CI 0·87–1·24, p=0·69). There were 39 adverse events in patients assigned to aggressive warming (17 of which were serious) and 54 in those assigned to routine thermal management (30 of which were serious). One serious adverse event, in an aggressively warmed patient, was deemed to be possibly related to thermal management. The incidence of a 30-day composite of major cardiovascular outcomes did not differ significantly in patients randomised to 35·5°C and to 37°C. At least over a 1·5°C range from very mild hypothermia to full normothermia, there was no evidence that any substantive outcome varied. Keeping core temperature at least 35·5°C in surgical patients appears sufficient. 3M and the Health and Medical Research Fund, Food and Health Bureau, Hong Kong. For the Chinese translation of the abstract see Supplementary Materials section.

Background To elucidate the incidence of acute kidney injury (AKI) after out-of-hospital cardiac arrest (OHCA) and to examine the impact of target temperature management (TTM) and early coronary angiography on renal function. Methods Post hoc analysis of the TTM trial, a multinational randomised controlled trial comparing target temperature of 33 °C versus 36 °C in patients with return of spontaneous circulation after OHCA. The impact of TTM and early angiography (within 6 h of OHCA) versus late or no angiography on the development of AKI during the 7-day period after OHCA was analysed. AKI was defined according to modified KDIGO criteria in patients surviving beyond day 2 after OHCA. Results Following exclusions, 853 of 939 patients enrolled in the main trial were analysed. Unadjusted analysis showed that significantly more patients in the 33 °C group had AKI compared to the 36 °C group [211/431 (49%) versus 170/422 (40%) p  = 0.01], with a worse severity ( p  = 0.018). After multivariable adjustment, the difference was not significant (odds ratio 0.75, 95% confidence interval 0.54–1.06, p  = 0.10]. Five hundred seventeen patients underwent early coronary angiography. Although the unadjusted analysis showed less AKI and less severe AKI in patients who underwent early angiography compared to patients with late or no angiography, in adjusted analyses, early angiography was not an independent risk factor for AKI (odds ratio 0.73, 95% confidence interval 0.50–1.05, p  = 0.09). Conclusions In OHCA survivors, TTM at 33 °C compared to management at 36 °C did not show different rates of AKI and early angiography was not associated with an increased risk of AKI. Trial registration NCT01020916 . Registered on www.ClinicalTrials.gov 26 November 2009 (main trial).

Study designProspective multi-center trial.ObjectivesTo characterize the complication profile associated with modest systemic hypothermia after acute cervical SCI in a prospective multi-center study.SettingFive trauma centers in the United States.MethodsWe analyzed data from a prospective, multi-center trial on the use of modest systemic hypothermia for acute cervical SCI. Patients with acute cervical SCI were assigned to receive modest systemic hypothermia (33 C) or standard of care medical treatment. Patients in the hypothermia group were cooled to 33 C and maintained at the target temperature for 48 h. Complication profile and the rate of complications within the first 6 weeks after injury were compared between the two groups. Multiple regression analysis was performed to determine risk factors for complications after injury.ResultsFifty patients (hypothermia: 27, control: 23) were analyzed for this study. Median age was significantly lower in the hypothermia arm (39 vs 59 years, p = 0.02). Respiratory complications were the most common (hypothermia: 55.6% vs control: 52.2%, p = 0.81). The rate of deep vein thrombosis was not significantly different between the two groups (hypothermia: 14.8% vs control 17.4%, p = 0.71). The rate of complications was not statistically different between the two groups.ConclusionIn this prospective multi-center controlled trial, preliminary data show that modest systemic hypothermia was not associated with increased risk of complications within the first 6 weeks after acute cervical SCI.Trial informationThe study is registered on clinicaltrials.gov NCT02991690. University of Miami IRB (Central IRB) approval No.: 20160758. Emory University IRB #IRB00093786.

Background An ancillary study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia examined the hypothesis that neonates randomized to receive erythropoietin (Epo) would have a lower seizure risk and burden compared with neonates who received placebo. Methods Electroencephalograms (EEGs) from 7/17 HEAL trial centers were reviewed. Seizure presence was compared across treatment groups using a logistic regression model adjusting for treatment, HIE severity, center, and seizure burden prior to the first dose. Among neonates with seizures, differences across treatment groups in median maximal hourly seizure burden were assessed using adjusted quantile regression models. Results Forty-six of 150 (31%) neonates had EEG seizures (31% in Epo vs 30% in placebo, p  = 0.96). Maximal hourly seizure burden after the study drug was not significantly different between groups (median 11.4 for Epo, IQR: 5.6, 18.1 vs median 9.7, IQR: 4.9, 21.0 min/h for placebo). Conclusion In neonates with HIE treated with hypothermia who were randomized to Epo or placebo, we found no meaningful between-group difference in seizure risk or burden. These findings are consistent with overall trial results, which do not support Epo use for neonates with HIE undergoing therapeutic hypothermia. Impact In the HEAL trial of erythropoietin (Epo) vs placebo for neonates with encephalopathy presumed due to hypoxic-ischemic encephalopathy (HIE) who were also treated with therapeutic hypothermia, electrographic seizures were detected in 31%, which is lower than most prior studies. Epo did not reduce the proportion of neonates with acute provoked seizures (31% in Epo vs 30% in placebo) or maximal hourly seizure burden after the study drug (median 11.4, IQR 5.6, 18.1 for Epo vs median 9.7, IQR 4.9, 21.0 min/h for placebo). There was no anti- or pro-convulsant effect of Epo when combined with therapeutic hypothermia for HIE.

On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48–72 h with slow rewarming improved mortality in children after brain injury. In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6–15 years, 16–17 years]) to either hypothermia (rapidly cooled to 32–33°C for 48–72 h, then rewarmed by 0·5–1·0°C every 12–24 h) or normothermia (maintained at 36·5–37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742. The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events. Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury. National Institute of Neurological Disorders and Stroke and National Institutes of Health.

[This corrects the article DOI: 10.1371/journal.pone.0281977.].

Aim The aim of this study was to determine the population pharmacokinetics of darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy treated with hypothermia. Methods Neonates ≥36 weeks gestation and <12 h postpartum with moderate to severe hypoxic-ischemic encephalopathy who were undergoing hypothermia treatment were recruited in this randomized, multicenter, investigational, new drug pharmacokinetic study. Two intravenous darbepoetin alfa treatment groups were evaluated: 2 and 10 µg/kg. Serum erythropoietin concentrations were measured using an enzyme-linked immunosorbent assay. Monolix 4.3.1 was used to estimate darbepoetin alfa clearance and volume of distribution. Covariates tested included: birthweight, gestational age, postnatal age, postmenstrual age, sex, Sarnat score, and study site. Results Darbepoetin alfa pharmacokinetics were well described by a one-compartment model with exponential error. Clearance and the volume of distribution were scaled by birthweight (centered on the mean) a priori. Additionally, gestational age (also centered on the mean) significantly affected darbepoetin alfa clearance. Clearance and volume of distribution were estimated as 0.0465 L/h (95 % confidence interval 0.0392–0.0537) and 1.58 L (95 % confidence interval 1.29–1.87), respectively. Conclusions A one-compartment model successfully described the pharmacokinetics of darbepoetin alfa among hypothermic neonates treated for hypoxic-ischemic encephalopathy. Clearance decreased with increasing gestational age.