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    Early electroencephalogram does not reliably differentiate outcomes in post-hypoxic myoclonus. Dalic Linda J,Fennessy Gerard,Edmonds Mark,Carney Patrick,Opdam Helen,Archer John Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine OBJECTIVE:Prognostication in patients with post-hypoxic brain injury remains difficult; yet, clinicians are commonly asked to guide decisions regarding withdrawal of life support. We aimed to assess whether electroencephalogram (EEG) is a useful tool in predicting neurological outcome in patients with post-hypoxic myoclonus (PHM). DESIGN AND SETTING:This study was conducted as part of an internal hospital audit assessing therapeutic hypothermia in patients with hypoxic cardiac arrest. PARTICIPANTS:We identified 20 patients with PHM and evaluated their initial routine EEG. MAIN OUTCOME MEASURES:Three blinded neurologists independently assessed EEGs and scored them using the standardised critical care EEG terminology from the American Clinical Neurophysiology Society (2012 version) and the EEG patterns identified by the Target Temperature Management (TTM) trial group. Glasgow Outcome Scale (GOS) scores were used to assess neurological outcome at 30 and 90 days. Mortality rates at these time points were also documented. RESULTS:We found that the majority of patients (18/20) with PHM had an initial EEG that was "highly malignant" or "malignant", but outcomes at 30 and 90 days were not universally fatal. Six patients were alive at 30 days, and five at 90 days. Of the latter, two patients had moderate disability (GOS score 4) and one improved from a GOS score of 3 to 5, with only low disability. Two patients with "benign" EEGs had unchanged GOS scores of 3 at 30 and 90 days, indicating severe disability. CONCLUSION:This study shows that PHM is associated with a poor but not universally fatal prognosis. Early EEG does not reliably distinguish between good and poor outcomes.
    Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy? Davies Anthony,Wassink Guido,Bennet Laura,Gunn Alistair J,Davidson Joanne O Neural regeneration research Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability. Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy; however, many infants still experience lifelong disabilities to movement, sensation and cognition. Clinical guidelines, based on strong clinical and preclinical evidence, recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours, with a target brain temperature of 33.5 ± 0.5°C for infants with moderate to severe hypoxic-ischemic encephalopathy. The clinical guidelines also recommend that infants be rewarmed at a rate of 0.5°C per hour, but this is not based on strong evidence. There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy. Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia. In this review, we evaluate the evidence for the optimal start time, duration and depth of hypothermia, and whether the rate of rewarming after treatment affects brain injury and neurological outcomes. 10.4103/1673-5374.257512
    Is hypothermia useful in malignant ischemic stroke? Current status and future perspectives. Jaramillo Arturo,Illanes Sergio,Díaz Violeta Journal of the neurological sciences BACKGROUND AND AIMS:In acute stroke patients, mild and moderate hypothermia with a body temperature (T core) target of 32 degrees C to 34 degrees C is being tested and has shown some promising results. The feasibility of MH to control of ICP increases in patients with malignant ischemic stroke has been proven, but controversy as to its effectiveness and safety still continues. The most recent results of clinical trials and possible future applications of MH in acute stroke patients are analyzed in this review. DESIGN, METHODS AND MATERIAL: A search in MEDLINE/PubMed was performed. The references of selected articles were investigated and the Cochrane Library searched. Articles including severe, massive, malignant or hemispheric ischemic stroke, induced hypothermia, and animal studies with focal cerebral or brain ischemic models were considered. RESULTS:196 patients with ischemic stroke treated with hypothermia have been reported in eleven small clinical studies, with a mild benefit of MH over the mortality rate and final outcome. CONCLUSIONS:Moderate hypothermia ameliorates ischemic injury by multiple mechanisms. Treatment of acute ischemic stroke patients is feasible, and additional studies, including randomized clinical trials, are warranted. 10.1016/j.jns.2007.08.037
    [Effect and significance of mild hypothermia on cerebral blood flow velocity and cerebral extraction rate of oxygen in patients with severe subarachnoid hemorrhage]. Shui T,Guo Z Y,Zhang G Z,Chen Q,Li B Zhonghua yi xue za zhi Through studying the variations of cerebral blood flow velocity and cerebral extraction rate of oxygen to investigate the effect and mechanism of mild hypothermia therapy on early brain injury (EBI) and cerebral vasospasm (CVS) induced by sever subarachnoid hemorrhage (SAH). A total of 62 adult patients admitted in the Department of Neurosurgery of Tianjin TEDA Hospital from January 2014 to December 2016 with severe SAH without contraindications of hypothermia therapy were randomly divided into mild hypothermia (MH) group of 30 cases and routine treatment (RT) group of 32 cases.The general data were no significant difference.The routine treatment group got bloody cerebrospinal fluid drainage, spasmolysis, 3H treatment, etc.Besides conventional treatment, MH group got mild hypothermia therapy started on the day of admission within 2-8 hours, lower rectal temperature and maintained at (35±1) ℃, maintain 5-7 d. The mean velocity of middle cerebral artery blood flow (VmMCA) and Lindergaard index of two groups were detected by transcranial Doppler to indirectly evaluate the degree and evolution of CVS.Blood gas analysis was performed to obtain the blood oxygen content of the artery and jugular vein (CaO(2)/CjvO(2)) in the two groups at the same time, and the cerebral extraction rate of oxygen (CERO(2)) = (CaO(2)-CjvO(2))/CaO(2) was calculated. Within 5 times of admission d1, d2, d3, d7 and d14, mean results of VmMCA of RT group were significantly higher than those of the MH group at d2, d3, d7 and d14 on statistics.The changes of CERO(2) between MH group and RT group during the observation period were compared at the same time: there was no significant difference between d1 and d14 (>0.05); at d2, d3 and d7 showed marked differences, and that of the MH group was significantly lower than that of the RT group' (<0.01). The correlation analysis showed that it had a weak correlation between CERO(2) and VmMCA (>0.05) in the MH group, and CERO(2) was significantly positively correlated with VmMCA in the RT group (<0.01). MH therapy has a positive significance to reduce the incidence, degree and the duration of CVS.The relationship between CVS and the degree of hypoxia in brain was broken by the MH therapy to reduce the adverse effects of EBI through reducing metabolism, thereby alleviating hypoxia damage in brain tissue.Setting the appropriate target temperature and the course of treatment and then the gentle rewarming process can reduce the incidence of complications of hypothermia therapy. 10.3760/cma.j.issn.0376-2491.2018.19.007
    Successful use of prolonged mild hypothermia in a patient with severe head injury and diffuse brain swelling. Case report. Murakami Mamoru,Tsukahara Tetsuya,Ishikura Hiroyasu,Hatano Taketo,Nakakuki Takuya,Ogino Eiji,Aoyama Takako Neurologia medico-chirurgica A 19-year-old female was admitted to our hospital after severe head injury in a traffic accident. On admission, she had no spontaneous respiration, but did have heart beat with a blood pressure of 100/60 mmHg. Neurological examination demonstrated that the Glasgow Coma Scale score was 3 and her pupils were fixed and dilated. Computed tomography (CT) showed diffuse brain swelling with disappearance of the perimesencephalic cistern. Chest CT showed bilateral lung contusions. Mild hypothermia with a target temperature of 33 degrees C was immediately induced, and was continued for 28 days to control the persistent increase in intracranial pressure (ICP). Subsequently, she recovered, and 20 months after admission, could speak and walk with slight hemiparesis on the left. Prolonged mild hypothermia may be effective to control persistent increase in ICP due to diffuse brain swelling. 10.2176/nmc.47.116
    Optimization of brain metabolism using metabolic-targeted therapeutic hypothermia can reduce mortality from traumatic brain injury. Feng Jin-Zhou,Wang Wen-Yuan,Zeng Jun,Zhou Zhi-Yuan,Peng Jin,Yang Hao,Deng Peng-Chi,Li Shi-Jun,Lu Charles D,Jiang Hua The journal of trauma and acute care surgery BACKGROUND:Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target because optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof. METHODS:Severe TBI patients (Glasgow Coma Scale score, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group, hypothermia therapy target of 32°C to 35°C body temperature. Brain and circulatory metabolic pool blood samples were collected at baseline and on days 1, 3, and 7 during the hypothermia treatment, which were selected randomly from a subgroup of MTHT and BTHT groups. The primary outcome was mortality. Using H nuclear magnetic resonance technology, we tracked and located the disturbances of metabolic networks. RESULTS:Eighty-eight severe TBI patients were recruited and analyzed from December 2013 to December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42 years; 69.32% men; mean Glasgow Coma Scale score, 6.17 ± 1.02). The mortality was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%; p = 0.049). From these, eight cases of MTHT and six cases from BTHT group were enrolled for metabolomics analysis, which showed a significant difference between the brain and circulatory metabolic patterns in MTHT group on day 7 based on the model parameters and scores plots. Finally, metabolites representing potential neuroprotective monitoring parameters for hypothermia treatment were identified through H nuclear magnetic resonance metabolomics. CONCLUSION:MTHT can significantly reduce the mortality of severe TBI patients. Metabolomics research showed that this strategy could effectively improve brain metabolism, suggesting that reducing the metabolic rate to 50% to 60% should be set as the hypothermia therapy target. LEVEL OF EVIDENCE:Therapeutic study, Level I. 10.1097/TA.0000000000001522