Therapeutic hypothermia and temperature management最新文献

We aimed to compare serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels in neonates with different hypoxic-ischemic encephalopathy (HIE) stages undergoing therapeutic hypothermia (TH), and to evaluate the TSH and fT4 levels in neonates with HIE/TH in comparison with a control group. This was a retrospective study conducted between January 2020 and December 2022. The neonates with HIE/TH constituted the study group and the neonates with transient tachypnea of the newborn (TTN) constituted the control group. The study group consisted of neonates with stage 2 and stage 3 HIE. Serum TSH and fT4 levels measured at postnatal fifth day were compared between the groups. Of the 202 (47.1%) neonates included in the study group, 144 (71.3%) had stage 2 HIE and 58 (28.7%) had stage 3 HIE. In the control group, there were 227 (52.9%) newborns. Serum TSH and fT4 levels were found to be lower in the newborns with stage 3 HIE compared with those with stage 2 HIE (p = 0.015, 0.002, respectively). Although the serum TSH level was higher in the newborns with HIE compared with the newborns with TTN, serum fT4 levels did not change between the groups (p = < 0.001, 0.14, respectively). When we made the analysis according to the reference intervals, HIE/TH was associated with higher rates of TSH elevation compared with TTN, and the difference was more pronounced in stage 2 HIE/TH (p < 0.001). Although stage 3 HIE/TH was significantly associated with higher rates of low fT4 compared with TTN (p = 0.006), this relationship was not significant between stage 2 HIE/TH and TTN. It would be reasonable to interpret thyroid function tests performed on the fifth day with caution in newborns with HIE/TH, because higher TSH and lower fT4 levels on the fifth day in this patient group may result in unnecessary repetition of tests.

This study aimed to explore the antipyretic and anti-inflammatory effects of rectal administration of Reduning injection in feverish rats induced by lipopolysaccharide (LPS), and observe the temperature changes and inflammatory indexes. The selected rats were randomly divided into 6 groups, with 10 rats in each group, named as normal empty group, model group, intravenous group (2 mL/kg), low-dose enema group (1 mL/kg), middle-dose enema group (2 mL/kg), and high-dose enema group (4 mL/kg). The hourly temperature variations in rats injected with LPS in the abdomen were recorded. Five hours later, blood samples from the abdominal aorta were collected to monitor immunoglobulin M (IgM), immunoglobulin A (IgA), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. At 5 hours, the fever peak induced by LPS appeared, and obvious antipyretic effects were observed; the effect was optimal in the medium dose enema group at 4 hours (p < 0.05); the IgM value in the enema groups, the intravenous group, and normal empty group was significantly lower than that in the model group; the IgA value in each group was higher than that in the model group, but there was no statistical significance (p > 0.05); values of IL-6 and TNF-α in each group were lower than those in the model group, and the difference was statistically significant except for the high-dose enema group (p > 0.05). Low-dose and medium-dose rectal administration of Reduning injection have inhibitory effects on IL-6, TNF-α, and IgM in feverish rats induced by LPS, but there is no obvious difference compared to intravenous administration and it could achieve an anti-inflammatory effect. There is a possibility of enhancing IgA immunity with rectal administration, but there is no obvious difference compared to intravenous administration, and rectal administration has no significant effect on mucosal immunity.

To assess the effectiveness and molecular mechanisms of mild hypothermia and remote ischemic postconditioning (RIPC) in patients with acute ischemic stroke (AIS) who have undergone thrombolysis therapy. A total of 58 AIS patients who received recombinant tissue plasmin activator (rt-PA) intravenous thrombolysis were included in this prospective study. Participants were randomly allocated to the experimental group (rt-PA intravenous thrombolysis plus mild hypothermic ice cap plus remote ischemic brain protection, n = 30) and the control group (rt-PA intravenous thrombolysis plus 0.9% saline, n = 28). The RIPC was performed for 14 consecutive days on both upper limb arteries spaced 2 minutes apart. Five cycles of ischemia-reperfusion were performed sequentially (2-2, 3-3, 4-4, 5-5, 5-0 minutes, respectively). The outcome measures of the National Institute of Health stroke scale (NIHSS) score, volume of cerebral infarction, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β, tumor necrosis factor α, nuclear factors kappa B (NF-κB), and NOD-1ike receptor pyrin 3 (NLRP3) were evaluated at different time points after treatment. Similarly, the 90-day modified Rankin Scale (mRS) scores were compared between the two groups. After treatment, the NIHSS score, MDA, NF-κB, and NLRP3 levels in the experimental group were significantly lower than those in the control group (p < 0.05). While the SOD in the experimental group was significantly higher than in the control group (p < 0.05), the NIHSS scores decreased within groups (all p < 0.05) in both experimental and control groups. The 90-day mRS score (0-2 points) in the experimental group was significantly higher than that in the control group (73.33% vs. 53.57%, p < 0.05) and no significant differences were observed in the safety indices between the two groups (all p > 0.05). Our study shows that combining mild hypothermia and RIPC has a positive effect on brain protection and can significantly reduce the oxidative stress and associated outburst of inflammatory response. The Clinical Trial Registration number is ChiCTR2300073136.

There is a paucity of evidence regarding the utility of targeted temperature management (TTM) in COVID-19 patients who suffer cardiac arrest. This systematic review and meta-analysis aimed to use the available data of how temperature predicts outcomes in COVID-19 patients and the association between active cooling and outcomes in non-COVID-19 cardiac arrest patients to give recommendations for the utility of TTM in COVID-19 survivors of cardiac arrest. The PubMed, Embase, and Web of Science databases were queried in August 2022 for two separate searches: (1) temperature as a predictor of clinical outcomes in COVID-19 and (2) active cooling after return of spontaneous circulation (ROSC) in non-COVID-19. Forest plots were generated to summarize the results. Of the 4209 abstracts screened, none assessed the target population of TTM in COVID-19 victims of cardiac arrest. One retrospective cohort study evaluated hyperthermia in critically ill COVID-19 patients, two retrospective cohort studies evaluated hypothermia in septic COVID-19 patients, and 20 randomized controlled trials evaluated active cooling in non-COVID-19 patients after ROSC. Risk of death was higher in COVID-19 patients who presented with hyperthermia (risk ratio [RR] = 1.87) or hypothermia (RR = 1.77; p < 0.001). In non-COVID-19 victims of cardiac arrest, there was no significant difference in mortality (RR = 0.94; p = 0.098) or favorable neurological outcome (RR = 1.05; p = 0.41) with active cooling after ROSC. Further studies are needed to evaluate TTM in COVID-19 victims of cardiac arrest. However, given the available evidence that hyperthermia or hypothermia in COVID-19 patients is associated with increased mortality as well as our findings suggesting limited utility for active cooling in non-COVID-19 cardiac arrest patients, we posit that TTM to normothermia (core body temperature ∼37°C) would most likely be optimal for the best outcomes in COVID-19 survivors of cardiac arrest.

Current guidelines strongly recommend providing targeted temperature management (TTM) after cardiac arrest, but hypothalamic dysregulation may confound TTM's impact on a patient's ultimate outcome. Although time to reach target temperature has largely been viewed as a process measure for TTM protocols, the difference between initial presenting temperature and target temperature (Δ-temperature) may be a potential surrogate marker of hypothalamic dysregulation. We performed a retrospective observational study to explore whether Δ-temperature was associated with neurologic outcomes and mortality. We included 86 patients (53 with out-of-hospital cardiac arrest [OHCA] and 33 with in-hospital cardiac arrest [IHCA]) in our analysis; more than half of the patients were cooled to 33°C (56.9% in OHCA and 57.6% in IHCA). In univariate logistic regression analysis, Δ-temperature alone did not appear to be statistically associated with mortality or neurologic outcomes regardless of target temperature. In exploratory analysis, longer time from TTM initiation-to-target was associated with worse neurological outcomes in the 33°C target (odds ratio = 0.996, 95% confidence interval = 0.992-1.000). Further research investigating the impact of hypothalamic dysregulation and Δ-temperature as well as the rate of cooling may be warranted to elucidate additional factors contributing to outcomes after cardiac arrest. In addition, our study population was noted to have a higher proportion of Asians and Native Hawaiians/Pacific Islanders, with a potential disparity in outcomes. Future studies may be warranted to ensure generalizability of TTM protocols and findings across populations.

Therapeutic hypothermia (TH) is the only currently approved treatment for neonatal hypoxic-ischemic encephalopathy (HIE) and must be started within 6 hours to optimize effectiveness. This narrow therapeutic window often requires initiation of TH before or during transport. The goal of this study was to assess the effects of servo-controlled TH versus passive hypothermia during transport on short-term outcomes in newborns with HIE. This was a single-center retrospective case-control study of neonates with HIE treated with active or passive TH during transport. Primary outcomes included brain injury on magnetic resonance imaging (MRI) and presence of seizures. Seventy-six neonates were included-13 active and 63 passive. The active TH group was more likely to arrive within goal temperature. No difference was noted between groups in seizures or TH complications. Active TH was associated with increased injury on MRI. Active TH resulted in tighter temperature control, but no improvement in short-term outcomes in our cohort. The MRI findings may be due to differences in overall disease severity, which could not be adjusted for, given the modest sample size.

Decades of animal research show therapeutic hypothermia (TH) to be potently neuroprotective after cerebral ischemic injuries. While there have been some translational successes, clinical efficacy after ischemic stroke is unclear. One potential reason for translational failures could be insufficient optimization of dosing parameters. In this study, we conducted a systematic review of the PubMed database to identify all preclinical controlled studies that compared multiple TH durations following focal ischemia, with treatment beginning at least 1 hour after ischemic onset. Six studies met our inclusion criteria. In these six studies, six of seven experiments demonstrated an increase in cerebroprotection at the longest duration tested. The average effect size (mean Cohen's d ± 95% confidence interval) at the shortest and longest durations was 0.4 ± 0.3 and 1.9 ± 1.1, respectively. At the longest durations, this corresponded to percent infarct volume reductions between 31.2% and 83.9%. Our analysis counters previous meta-analytic findings that there is no relationship, or an inverse relationship between TH duration and effect size. However, underreporting often led to high or unclear risks of bias for each study as gauged by the SYRCLE Risk of Bias tool. We also found a lack of investigations of the interactions between duration and other treatment considerations (e.g., method, delay, and ischemic severity). With consideration of methodological limitations, an understanding of the relationships between treatment parameters is necessary to determine proper "dosage" of TH, and should be further studied, considering clinical failures that contrast with strong cerebroprotective results in most animal studies.

Targeted temperature management (TTM) has been proposed to reduce mortality and improve neurological outcomes in postcardiac arrest and other critically ill patients. TTM implementation may vary considerably among hospitals, and "high-quality TTM" definitions are inconsistent. This systematic literature review in relevant critical care conditions evaluated the approaches to and definitions of TTM quality with respect to fever prevention and the maintenance of precise temperature control. Current evidence on the quality of fever management associated with TTM in cardiac arrest, traumatic brain injury, stroke, sepsis, and critical care more generally was examined. Searches were conducted in Embase and PubMed (2016 to 2021) following PRISMA guidelines. In total, 37 studies were identified and included, with 35 focusing on postarrest care. Frequently-reported TTM quality outcomes included the number of patients with rebound hyperthermia, deviation from target temperature, post-TTM body temperatures, and number of patients achieving target temperature. Surface and intravascular cooling were used in 13 studies, while one study used surface and extracorporeal cooling and one study used surface cooling and antipyretics. Surface and intravascular methods had comparable rates of achieving target temperature and maintaining temperature. A single study showed that patients with surface cooling had a lower incidence of rebound hyperthermia. This systematic literature review largely identified cardiac arrest literature demonstrating fever prevention with multiple TTM approaches. There was substantial heterogeneity in the definitions and delivery of quality TTM. Further research is required to define quality TTM across multiple elements, including achieving target temperature, maintaining target temperature, and preventing rebound hyperthermia.

Fibroblast Growth Factor 21 (FGF21) is a neuroprotective hormone induced by cold exposure that targets the β-klotho co-receptor. β-klotho is abundant in the newborn brain but decreases rapidly with age. RNA-Binding Motif 3 (RBM3) is a potent neuroprotectant upregulated by FGF21 in hypothermic conditions. We characterized serum FGF21 and RBM3 levels in patients enrolled in a prospective multi-center study of pediatric cardiac arrest (CA) via a secondary analysis of samples collected to evaluate brain injury biomarkers. Patients (n = 111) with remnant serum samples available from at least two of three available timepoints (0-24, 24-48 or 48-72 hours post-resuscitation) were included. Serum samples from 20 healthy controls were used for comparison. FGF21 was measured by Luminex and internally validated enzyme-linked immunoassay (ELISA). RBM3 was measured by internally validated ELISA. Of postarrest patients, 98 were managed with normothermia, while 13 were treated with therapeutic hypothermia (TH). FGF21 increased >20-fold in the first 24 hours postarrest versus controls (681 pg/mL [200-1864] vs. 29 pg/mL [15-51], n = 99 vs. 19, respectively, p < 0.0001, median [interquartile range]) with no difference in RBM3. FGF21 did not differ by sex, while RBM3 was increased in females versus males at 48-72 hours postarrest (1866 pg/mL [873-5176] vs. 1045 pg/mL [535-2728], n = 40 vs. 54, respectively, p < 0.05). Patients requiring extracorporeal membrane oxygenation (ECMO) postresuscitation had increased FGF21 versus those who did not at 48-72 hours (6550 pg/mL [1455-66,781] vs. 1213 pg/mL [480-3117], n = 7 vs 74, respectively, p < 0.05). FGF21 and RBM3 did not correlate (Spearman's rho = 0.004, p = 0.97). We conclude that in a multi-center study of pediatric CA patients where normothermic targeted temperature management was largely used, FGF21 was markedly increased postarrest versus control and highest in patients requiring ECMO postresuscitation. RBM3 was sex-dependent. We provide a framework for future studies examining the effect of TH on FGF21 or use of FGF21 therapy after pediatric CA.

To explore the effect of the temperature chain management scheme on inadvertent perioperative hypothermia (IPH) during robot-assisted radical resection of urological tumors. Fifty male patients who underwent elective robot-assisted radical prostatectomy (RARP) or robot-assisted radical cystectomy (RARC) surgery from February 2022 to March 2023 in a teaching hospital were enrolled and randomized to receive either intraoperative warming, including forced-air warming blanket and prewarming fluid (group C) or the temperature chain management involving an active warming bunch covering the whole perioperative period (group T). Comparing the core temperature, IPH rates, the incidence of shivering, recovery from anesthesia, and thermal between the two groups. Perioperative core temperature of group T was higher compared with group C (p < 0.05); IPH rates and the incidence of shivering in postanesthesia care unit (PACU) of group T were lower compared with group C (p < 0.05); group T scored higher in thermal comfort compared with group C after PACU 15 minutes, after PACU 30 minutes, and when leaving the PACU (p < 0.05); group T took shorter time on recovering from anesthesia (p < 0.05). Temperature chain management could reduce IPH and postoperative complications during RARP and RARC.