Therapeutic hypothermia and temperature management最新文献

Although most commonly associated with infection, elevated temperature and fever also occur in a variety of critically ill populations. Prior studies have suggested that fever and elevated temperature may be detrimental to critically ill patients and can lead to poor outcomes, but the evidence surrounding the association of fever with outcomes is rapidly evolving. To broadly assess potential associations of elevated temperature and fever with outcomes in critically ill adult patients, we performed a systematic literature review focusing on traumatic brain injury, stroke (ischemic and hemorrhagic), cardiac arrest, sepsis, and general intensive care unit (ICU) patients. Searches were conducted in Embase^® and PubMed^® from 2016 to 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including dual-screening of abstracts, full texts, and extracted data. In total, 60 studies assessing traumatic brain injury and stroke (24), cardiac arrest (8), sepsis (22), and general ICU (6) patients were included. Mortality, functional, or neurological status and length of stay were the most frequently reported outcomes. Elevated temperature and fever were associated with poor clinical outcomes in patients with traumatic brain injury, stroke, and cardiac arrest but not in patients with sepsis. Although a causal relationship between elevated temperature and poor outcomes cannot be definitively established, the association observed in this systematic literature review supports the concept that management of elevated temperature may factor in avoidance of detrimental outcomes in multiple critically ill populations. The analysis also highlights gaps in our understanding of fever and elevated temperature in critically ill adult patients.

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.

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.

The study subject was a healthy, 47-year-old man, a low temperature Guinness World Record holder. He spent 50 days alone in Rovaniemi, Lapland, and functioned in the ambient temperature ranging from +2°C to -37°C. He did not use sources of heat, he did not eat warm meals or drink hot water, and did not dry his clothes. He slept in an igloo, on an ice cover of 20-30 cm. He spent 10 hours a day in a sleeping bag and for the remaining time he walked, skied, or rode a bicycle, and practiced swimming. The aim of the study was a laboratory assessment of renal capacity in a man exposed to long-term extremely low ambient temperatures. The study was approved by the Ethical Committee at the Regional Medical Chamber in Krakow, Poland (approval No.: 194/KBL/OIL/2019). Twice during the observation, urine and blood were collected and analyzed: before and after the prolonged exposure to extremely low ambient temperatures. Changes were seen in many blood and urine parameters, but in urine, they were more significant. In urine, decreased values of sodium (by 53.9%), potassium (by 22.6%), creatinine (by 65.5%), urea (by 61.3%), uric acid (by 58.4%), and protein (by 50%) were observed. Neutrophil gelatinase-associated lipocalin (NGAL) increased by 34%. Absence of calcium oxalate excretion was reported relative to the value before the exposure to cold. In blood, increased values of interleukin-6 (by 60%) and β-2-microglobulin (by 26.9%) were observed. Erythropoietin decreased by 22.4%. No changes were noted in estimated glomerular filtration rate. The study subject lost 10 kg in weight. On the basis of the results obtained during the observation, it can be determined that the probable cause of changes in the laboratory results of the subject was the diet used, and not a dysfunction of the excretory system. The body weight loss and activation of compensating mechanisms focused on saving vitally important diet components, caused by the insufficient diet, exclude the theory of a negative effect of exposure to extremely low temperatures on renal filtration function.

Continuous renal replacement therapy (CRRT) is a commonly used therapeutic modality in the pediatric intensive care unit (PICU) for the treatment of severe acute kidney injury, as well as for addressing metabolic abnormalities, fluid-electrolyte imbalances, and acid-base disorders. According to reports, therapeutic hypothermia treatment has demonstrated the ability to decrease cellular metabolism, oxygen consumption, formation of free radicals, cell death, and inflammatory signals. The study encompassed all individuals who underwent CRRT at both Manisa City Hospital and Manisa Celal Bayar University Hospital throughout the period from February 2021 to November 2022. A total of 14 patients who received CRRT were subjected to a warming procedure utilizing an external blanket and an external heater attached to the CRRT venous return line, resulting in the attainment of a body temperature exceeding 36°C. Therapeutic hypothermia was implemented on 12 patients to maintain their body temperature within the range of 32-35°C. The study population exhibited a median age of 24.5 months, with males comprising 61.5% of the sample. A therapeutic hypothermia treatment was administered to a cohort of 12 patients. The patients who had therapeutic hypothermia exhibited a significantly reduced vasoactive-inotropic score (p = 0.038). Patients who did not receive therapeutic hypothermia exhibited a prolonged need for mechanical ventilation (p = 0.020). The duration of stay in the PICU for patients who underwent therapeutic hypothermia was shown to be considerably shorter compared to those who did not receive therapeutic hypothermia (p = 0.047). The potential efficacy of moderate therapeutic hypothermia appears promising, particularly in the context of patients who are receiving CRRT for severe sepsis and acute respiratory distress syndrome. This is attributed to the anti-inflammatory properties and hypometabolic effects associated with this intervention. To the best of our current understanding, this study represents the initial investigation showcasing the effectiveness of combining therapeutic hypothermia with CRRT in the pediatric population.

Therapeutic hypothermia (TH) mitigates damage in ischemic stroke models. However, safer and easier TH methods (e.g., pharmacological) are needed to circumvent physical cooling complications. This study evaluated systemic and pharmacologically induced TH using the adenosine A₁ receptor agonist, N₆-cyclohexyladenosine (CHA), with control groups in male Sprague-Dawley rats. CHA was administered intraperitoneally 10 minutes following a 2-hour intraluminal middle cerebral artery occlusion. We used a 1.5 mg/kg induction dose, followed by three 1.0 mg/kg doses every 6 hours for a total of 4 doses, causing 20-24 hours of hypothermia. Animals assigned to physical hypothermia and CHA-hypothermia had similar induction rates and nadir temperatures, but forced cooling lasted ∼6 hours longer compared with CHA-treated animals. The divergence is likely attributable to individual differences in CHA metabolism, which led to varied durations at nadir, whereas physical hypothermia was better regulated. Physical hypothermia significantly reduced infarction (primary endpoint) on day 7 (mean reduction of 36.8 mm³ or 39% reduction; p = 0.021 vs. normothermic animals; Cohen's d = 0.75), whereas CHA-induced hypothermia did not (p = 0.33). Similarly, physical cooling improved neurological function (physical hypothermia median = 0, physical normothermia median = 2; p = 0.008) and CHA-induced cooling did not (p > 0.99). Our findings demonstrate that forced cooling was neuroprotective compared with controls, but prolonged CHA-induced cooling was not neuroprotective.

Prognostication studies of cardiac arrest patients have mainly focused on poor neurological outcomes. However, an optimistic prognosis for good outcome could provide both justification to maintain and escalate treatment and evidence-based support to persuade family members or legal surrogates after cardiac arrest. The aim of the study was to evaluate the utility of clinical examinations performed after return of spontaneous circulation (ROSC) in predicting good neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). This retrospective study included OHCA patients treated with TTM from 2009 to 2021. Initial clinical examination findings related to the Glasgow coma scale (GCS) motor score, pupillary light reflex, corneal reflex (CR) and breathing above the set ventilator rate were assessed immediately after ROSC and before the initiation of TTM. The primary outcome was good neurological outcome at 6 months after cardiac arrest. Of 350 patients included in the analysis, 119 (34%) experienced a good neurological outcome at 6 months after cardiac arrest. Among the parameters of the initial clinical examinations, specificity was the highest for the GCS motor score, and sensitivity was the highest for breathing above the set ventilator rate. A GCS motor score of >2 had a sensitivity of 42.0% (95% confidence interval [CI] = 33.0-51.4) and a specificity of 96.5% (95% CI = 93.3-98.5). Breathing above the set ventilator rate had a sensitivity of 84.0% (95% CI = 76.2-90.1) and a specificity of 69.7% (95% CI = 63.3-75.6). As the number of positive responses increased, the proportion of patients with good outcomes increased. Consequently, 87.0% of patients for whom all four examinations were positive experienced good outcomes. As a result, the initial clinical examinations predicted good neurological outcomes with a sensitivity of 42.0-84.0% and a specificity of 69.7-96.5%. When more examinations with positive results are achieved, a good neurological outcome can be expected.

Studies in infants with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia have generally focused on neurological outcomes. Although acute kidney injury (AKI) rate decreased in advent of therapeutic hypothermia (TH), it is still a common and important entity. In this retrospective study, we aimed to investigate the risk factors for AKI in HIE patients treated with hypothermia. Infants treated with TH due to HIE were reviewed retrospectively and infants who developed AKI and not were compared. Ninety-six patients were enrolled in the study. AKI developed in 27 (28%) patients and 4 (14.8%) of them were stage III AKI. In the AKI group, gestational age of the patients was significantly higher (p = 0.035), the 1st minute Apgar score was significantly lower (p = 0.042), and convulsions (p = 0.002), amplitude-integrated electroencephalography disorders (p = 0.025), sepsis (p = 0.017), need for inotropic therapy (p = 0.001), need of invasive mechanical ventilation (p = 0.03), and systolic dysfunction in echocardiography (p = 0.022) were significantly higher. In logistic regression tests, Apgar score at the 1st minute was found to be independent risk factor for developing AKI. AKI has the potential to worsen the neurological damage and correlates with morbidities of perinatal asphyxia. It is important to determine the incidence and risk factors for developing AKI in this delicate group of patients to prevent further renal damage.

The study aimed to investigate the relationship of perioperative inadvertent hypothermia with anxiety and thermal and general comfort in surgical patients. Inadvertent perioperative hypothermia occurs after surgery and affects many patient outcomes. However, the relationship between hypothermia and anxiety has been given little attention. The research is of descriptive type. A total of 117 surgical patients who met the inclusion criteria were sampled and divided into two groups: hypothermic (n = 54) and normothermic (n = 63). Patients undergoing surgery were monitored for body temperature, systolic and diastolic blood pressure, heart rate, pain intensity, anxiety (Numeric Rating Scale [NRS] and State Anxiety Scale [SAI]), and comfort (Perianesthesia Comfort Questionnaire) levels. The groups were similar in terms of descriptive characteristics (p > 0.05). Among the patients undergoing surgical intervention, 46.1% were hypothermic. Compared with the normothermic group, the hypothermic group had significantly lower body temperature until the second postoperative hour, lower thermal comfort score until the third postoperative hour, and higher heart rate and anxiety (NRS) score until the first postoperative day. Furthermore, there was a significant difference between the groups in terms of pain intensity up to the first 30 minutes after surgery (p < 0.05). Moreover, there was no significant difference between the groups in terms of pre and postoperative day one anxiety (SAI) and Periantesthesia Comfort Scale mean scores (p > 0.05). The study findings showed that hypothermia affected thermal comfort up to the first 3 hours after surgery, pain intensity up to the first 30 minutes, and heart rate and anxiety (NRS) levels up to the first day.