Therapeutic hypothermia and temperature management最新文献

Temperature control is the only neuroprotective intervention suggested in current international guidelines for patients with return of spontaneous circulation after cardiac arrest, but the prevalence of temperature control therapy, temperature settings, and outcomes have not been clearly reported. We aimed to investigate changes over 7 years in provision of temperature control treatment among out-of-hospital cardiac arrest (OHCA) patients in Kanto region, Japan. Data of all adult OHCA patients who survived for more than 24 hours in the prospective cohort studies, SOS-KANTO 2012 (conducted from 2012 to 2013) and SOS-KANTO 2017 (conducted from 2019 to 2021), in Japan were included. We compared the prevalence of temperature control and the proportion of mild (≥35°C) and moderate (from 32°C to 34.9°C) hypothermia between the two study groups. We also performed a Cox regression analysis to evaluate 30-day mortality adjusted by temperature control therapy (none, moderate hypothermia, or mild hypothermia), age, sex, past medical history, witnessed status, bystander cardiopulmonary resuscitation, initial rhythm, location of arrest, and dataset (SOS-KANTO 2012 or 2017). We analyzed data from 2936 patients (n = 1710, SOS-KANTO 2012; n = 1226, SOS-KANTO 2017). Use of temperature control was lower (45.3% vs. 41.4%, p = 0.04), moderate hypothermia was lower (p < 0.01), and mild hypothermia was higher (p < 0.01) in SOS-KANTO 2017 compared with SOS-KANTO 2012. The survival rate was significantly higher for patients with mild (p < 0.01) and moderate (p < 0.01) hypothermia compared with those who did not receive temperature control therapy. Overall, the incidence of moderate hypothermia decreased and that of mild hypothermia increased and the use of temperature control decreased between the two studies conducted 7 years apart in the Kanto area, Japan. Temperature control management might improve survival of patients with OHCA.

The aim of this study was to describe whether whole-body hypothermia induced different respiratory changes in both invasively and noninvasively ventilated newborns and spontaneously breathing asphyxiated newborns during the course and after therapeutic hypothermia (TH). Data of 44 asphyxiated newborns undergoing TH at five different neonatal intensive care units in southern Italy were collected retrospectively between January 2018 and January 2021. For each type of ventilation, patient data on pH, partial pressure of Carbon Dioxide (pCO₂), base excess, lactate, and heart rate were recorded before cooling was started and at 24, 48, 72, and 96 hours from its initiation. Patients were later subgrouped into spontaneously breathing, noninvasively ventilated, and mechanically ventilated groups. The average trend of each parameter was reported, and a nonparametric statistical analysis of differences among groups before initiation and at 96 hours was performed using the Kruskal-Wallis test. Our results confirmed previous findings (supported by a small amount of literature) that no increase in requests for respiratory support is recorded in asphyxiated newborns undergoing TH during and after the rewarming phase. Furthermore, no statistically significant differences in the analyzed parameters were found among spontaneously breathing, noninvasively ventilated, and mechanically ventilated newborns, suggesting that changes in parameters might be attributable to TH itself rather than to an improvement in the respiratory condition over time; otherwise, a difference between spontaneously breathing patients, by definition "stable" from a respiratory point of view, and those requiring any type of respiratory support would have been expected.

This study investigates the clinical profile and predictors of gastrointestinal/hepatic morbidities and feeding outcomes among neonates with hypoxic-ischemic encephalopathy (HIE). A single-center retrospective chart review of consecutive neonates >35 weeks of gestation admitted with a diagnosis of HIE between January 1, 2015, and December 31, 2020, and treated with therapeutic hypothermia, if met the institutional eligibility criteria. Outcomes assessed included necrotizing enterocolitis (NEC), conjugated hyperbilirubinemia, hepatic dysfunction, assisted feeding at discharge, and time to reach full enteral and oral feeds. Among 240 eligible neonates (gestational age 38.7 [1.7] weeks, birth weight 3279 [551] g), 148 (62%) received hypothermia therapy, and 7 (3%) and 5 (2%) were diagnosed with stage 1 NEC and stage 2-3 NEC, respectively. Twenty-nine (12%) were discharged home with a gastrostomy/gavage tube, conjugated hyperbilirubinemia (first week 22 [9%], at discharge 19 [8%]), and hepatic dysfunction (74 [31%]). Time to reach full oral feeds was significantly longer in hypothermic neonates compared with neonates who did not receive hypothermia (9 [7-12] days vs. 4.5 [3-9] days, p < 0.0001). Factors significantly associated with NEC were renal failure (odds ratio [OR] 9.24, 95% confidence interval [CI] 2.7-33), hepatic dysfunction (OR 5.69, 95% CI 1.6-26), and thrombocytopenia (OR 3.6, 95% CI 1.1-12), but no significant association with hypothermia, severity of brain injury, or stage of encephalopathy. Transient conjugated hyperbilirubinemia, hepatic dysfunction within first week of life, and need for assistive feeding are more common than NEC in HIE. Risk of NEC was associated with the severity of end-organ dysfunction in the first week of life, rather than severity of brain injury and hypothermia therapy per se.

The Swiss National Asphyxia and Cooling Register was implemented in 2011. This study assessed quality indicators of the cooling process and (short-term) outcomes of neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) longitudinally over time in Switzerland. This is a multicenter national retrospective cohort study of prospectively collected register data. Quality indicators were defined for longitudinal comparison (2011-2014 vs. 2015-2018) of processes of TH and (short-term) outcomes of neonates with moderate-to-severe HIE. Five hundred seventy neonates receiving TH in 10 Swiss cooling centers were included (2011-2018). Four hundred forty-nine (449/570; 78.8%) neonates with moderate-to-severe HIE received TH according to the Swiss National Asphyxia and Cooling Register Protocol. Quality indicators of processes of TH improved in 2015-2018 (compared with 2011-2014): less passive cooling (p = 0.013), shorter time to reach target temperature (p = 0.002), and less over- or undercooling (p < 0.001). In 2015-2018, adherence to performing a cranial magnetic resonance imaging after rewarming improved (p < 0.001), whereas less cranial ultrasounds were performed on admission (p = 0.012). With regard to quality indicators of short-term outcomes, persistent pulmonary hypertension of the neonate was reduced (p = 0.003), and there was a trend toward less coagulopathy (p = 0.063) in 2015-2018. There was no statistically significant change in the remaining processes and outcomes. The Swiss National Asphyxia and Cooling Register is well implemented with good overall adherence to the treatment protocol. Management of TH improved longitudinally. Continuous reevaluation of register data is desirable for quality assessment, benchmarking, and maintaining international evidence-based quality standards.

Posthypoxic therapeutic hypothermia has been tested in newborn infants, with seven randomized trials showing consistent evidence of reduction in death, cerebral palsy, and cognitive impairment at school age. In contrast, randomized trials of hypothermia after cardiac arrest in adults have not shown consistent evidence of lasting neurological protection. The apparently greater effectiveness of therapeutic hypothermia in newborns may be due to important biological and clinical differences. One such difference is that adults are heavily colonized with microbes, and many have active inflammatory processes at the time of arrest, but few newborns are heavily colonized or infected at the time of birth. Inflammation can interfere with hypothermia's neuroprotection. A second difference is that apoptosis is more commonly the pathway of neuronal death in newborns than in adults. Hypothermia inhibits apoptosis but not necrosis. Newborns have a larger endogenous supply of stem cells (which reduce apoptosis) than adults and this may favor regeneration and protection from hypothermia and regeneration. A third difference is that immature oligodendroglia are more sensitive to free radical attack then mature oligodendroglia. Hypothermia reduces free radical release. In addition, immature brain has increased N-methyl-D-aspartate receptor subunits compared with adults and hypothermia reduces excitotoxic amino acids. Adults suffering cardiac arrest often have comorbidities such as diabetes, hypertension, and atherosclerosis, which complicate recovery, but newborn infants rarely have comorbidities before asphyxia. Adult hypothermia treatment may have been too short as no trial has cooled for longer than 48 hours, some only 24 or 12 hours, but neonatal therapeutic hypothermia has routinely lasted 72 hours. We hypothesize that this combination of differences favors the effectiveness of therapeutic hypothermia in newborn infants compared with adults.

Heatstroke (HS), a severe condition, can develop multiple organ dysfunction syndrome and death. However, at present, no early reliable index exists for risk stratification and prognosis. von Willebrand factor (vWF), a marker of vascular endothelial injury, is a key regulatory target of inflammation and coagulation, which is closely associated with the pathogenesis of HS. vWF was reported as a prognostic marker in several infectious and noninfectious severe illness such as COVID-19, sepsis, and trauma. Although early increased level of vWF is seen in HS, the relationship between vWF and mortality is to be elucidated. Clinical data of patients with HS in a tertiary hospital were recorded and analyzed. It was shown that plasma vWF concentrations at admission were significantly increased in the nonsurvivors (351% ± 105%) compared with survivors (278% ± 104%, p = 0.021). After multivariate logistic regression analysis it was shown that vWF (odds ratio [OR] = 1.010; 95% confidence interval [CI], 1.002-1.18; p = 0.017), hemoglobin (Hb) (OR = 0.954; 95% CI, 0.931-0.979; p < 0.001), and hematocrit (HCT) in blood (OR = 0.859; 95% CI, 0.790-0.934; p < 0.001) were independent factors of in-hospital mortality in HS. The nomogram based on vWF and Hb was constructed in patients with HS. The area under curve under the receiver operating characteristic of this prediction model was 0.860 (95% CI, 0.773-0.923) and cutoff was 0.15, with Youden index 0.5840, which were not significantly different to sequential organ failure assessment (p = 0.0644), Acute Physiology and Chronic Health Evaluation II (APACHE II) (p = 0.7976), and systemic inflammatory response syndrome (SIRS) scores (p = 0.3274). The prediction model that integrated vWF and Hb showed a better predicting efficiency than single variable, and a higher specificity (81.48%) than APACHE II (72.84%) and SIRS (72.84%) scores. In summary, vWF, as an independent risk factor for in-hospital mortality, combined with Hb, could effectively prognosis the mortality in HS patients at early stage.

In the setting of out-of-hospital cardiac arrest, therapeutic hypothermia (TH) has been shown to improve clinical outcomes. However, trials showing the advantage of TH did not include patients with cardiogenic shock (CS). We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared with the standard of care (SOC) in patients with CS. The primary outcome was the mortality rate (in-hospital, short-, and mid-term). The secondary outcomes were the TH-related complications, duration of Intensive Care Unit (ICU) stay, duration of mechanical ventilation (MV-days), and improvement in cardiac function. Relative risk (RR) or the standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A total of 7 clinical studies (3 RCTs included), and 712 patients (341 in the TH group and 371 in the SOC group) were included. As compared with the SOC, TH was not associated with a statistically significant improvement in the in-hospital (RR: 0.73%, 95% CI: 0.51-1.03; p = 0.08), short-term (RR: 0.90%, 95% CI: 0.75-1.06; p = 0.21), or mid-term (RR: 0.93%, 95% CI: 0.78-1.10; p = 0.38) mortality rates. Despite the improvement in the cardiac function in the TH group (SMD: 1.08, 95% CI: 0.02-2.1; p = 0.04), the TH strategy did not significantly shorten the MV days, or the ICU stay (p-values >0.05). Finally, there was a trend toward higher risks for infection, major bleeding, and the need for blood transfusion in the TH group. According to our meta-analysis of published clinical studies, TH is not beneficial in patients with CS and has a marginal safety profile. Larger-scale RCTs are needed to further clarify our results.

A 50-year-old man was admitted to our hospital with hypotension and bradycardia after receiving high doses of atenolol, amlodipine, and etizolam. He had a drug-induced J wave on electrocardiography and subsequently underwent cardiac arrest. The patient was successfully rescued by venoarterial extracorporeal membrane oxygenation (VA-ECMO) and a good neurological outcome was achieved with therapeutic hypothermia (TH). In patients with J waves, TH is thought to increase the J waves and cause fatal arrhythmias, but in this case, rapid cooling with VA-ECMO allowed the patient to successfully complete TH.

Targeted temperature management (TTM) may moderate the injury from out-of-hospital cardiac arrest. Slowing the metabolism has been a suggested effect. Nevertheless, studies have found higher lactate levels in patients cooled to 33°C compared with 36°C even days from TTM cessation. Larger studies have not been performed on the TTM's effect on the metabolome. Accordingly, to explore the effect of TTM, we used ultra-performance liquid-mass spectrometry in a substudy of 146 patients randomized in the TTM trial to either 33°C or 36°C for 24 hours and quantified 60 circulating metabolites at the time of hospital arrival (T₀) and 48 hours later (T₄₈). From T₀ to T_48, profound changes to the metabolome were observed: tricarboxylic acid (TCA) cycle metabolites, amino acids, uric acid, and carnitine species all decreased. TTM significantly modified these changes in nine metabolites (Benjamini-Hochberg corrected false discovery rate <0.05): branched amino acids valine and leucine levels dropped more in the 33°C arm (change [95% confidence interval]: -60.9 μM [-70.8 to -50.9] vs. -36.0 μM [-45.8 to -26.3] and -35.5 μM [-43.1 to -27.8] vs. -21.2 μM [-28.7 to -13.6], respectively), whereas the TCA metabolites including malic acid and 2-oxoglutaric acid remained higher for the first 48 hours (-7.7 μM [-9.7 to -5.7] vs. -10.4 μM [-12.4 to -8.4] and -3 μM [-4.3 to -1.7] vs. -3.7 μM [-5 to -2.3]). Prostaglandin E2 only dropped in the TTM 36°C group. The results show that TTM affects the metabolism hours after normothermia have been reached. Clinical Trial Number: NCT01020916.

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean body mass index 34.5 (±5.9) kg/m² with COVID-19 requiring mechanical ventilation were enrolled from September 2020 to February 2022. Patients were randomized 1:1 to standard of care or to receive core warming for 72 hours through an esophageal heat exchanger commonly utilized in critical care and surgical patients. The maximum target temperature was 39.8°C. A total of 10 patients received usual care and 9 patients received esophageal core warming. After 72 hours of warming, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratios were 197 (±32) and 134 (±13.4), cycle thresholds were 30.8 (±6.4) and 31.4 (±3.2), ICU mortalities were 40% and 44%, 30-day mortalities were 30% and 22%, and mean 30-day ventilator-free days were 11.9 (±12.6) and 6.8 (±10.2) for standard of care and warmed patients, respectively (p = NS). This pilot study suggests that core warming of patients with COVID-19 undergoing mechanical ventilation is feasible and appears safe. Optimizing time to achieve febrile-range temperature may require a multimodal temperature management strategy to further evaluate effects on outcome. ClinicalTrials.gov Identifier: NCT04494867.