Early enteral feeding guided by intestinal ultrasound during therapeutic hypothermia for hypoxic-ischemic encephalopathy in neonates / 中国新生儿科杂志

Objective:To study the safety and feasibility of early enteral feeding during therapeutic hypothermia guided by intestinal ultrasound in neonates with hypoxic-ischemic encephalopathy (HIE).Methods:From January 2019 to December 2021, neonates with HIE who received therapeutic hypothermia in the neonatology department of our hospital were retrospectively selected. They were assigned into the ultrasound-guided observation group (admitted from May 2020 to December 2021) and the control group (admitted from January 2019 to April 2020). In the ultrasound-guided observation group, intestinal ultrasound was performed during therapeutic hypothermia. Based on clinical manifestations and ultrasound results, a small amount of enteral feeding [20 ml/(kg·d)] was initiated and gradually increased to total enteral feeding after rewarming. In the control group, 5 ml (once every 3 h) of glucose and sodium chloride solution was given during 72 h of therapeutic hypothermia. After rewarming, enteral feeding was started and gradually increased to total enteral feeding without intestinal ultrasound. The time to start enteral feeding, the time to achieve total enteral feeding, the incidences of feeding intolerance, necrotizing enterocolitis (NEC) and late-onset sepsis were compared between the two groups.Results:A total of 17 cases were in the ultrasound-guided observation group and 18 cases in the control group. The median time to start enteral feeding and to achieve total enteral feeding in the ultrasound-guided observation group were earlier than the control group [36.0 (33.5, 39.0) h vs. 77.0 (74.0, 79.3) h, 6.0 (5.5, 6.5) d vs. 8.0 (7.0, 9.0) d, P<0.001]. No significant difference existed in the incidence of feeding intolerance between the two groups. Neither groups had NEC or late-onset sepsis. Conclusions:Early enteral feeding during therapeutic hypothermia in neonates with HIE is safe and feasible. Intestinal ultrasound helps implementing feeding plan and achieving early total enteral feeding.

Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming.@*RESULTS@#There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018).@*CONCLUSIONS@#Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

Unraveling quad fever: Severe hyperthermia after traumatic cervical spinal cord injury / 中华创伤杂志(英文版)

PURPOSE@#There are many infectious and inflammatory causes for elevated core-body temperatures, though they rarely pass 40 ℃ (104 ℉). The term "quad fever" is used for extreme hyperpyrexia in the setting of acute cervical spinal cord injuries (SCIs). The traditional methods of treating hyperpyrexia are often ineffective and reported morbidity and mortality rates approach 100%. This study aims to identify the incidence of elevated temperatures in SCIs at our institution and assess the effectiveness of using a non-invasive dry water temperature management system as a treatment modality with mortality.@*METHODS@#A retrospective analysis of acute SCI patients requiring surgical intensive care unit admission who experienced fevers ≥ 40 ℃ (104 ℉) were compared to patients with maximum temperatures < 40 ℃. Patients ≥18 years old who sustained an acute traumatic SCI were included in this study. Patients who expired in the emergency department; had a SCI without radiologic abnormality; had neuropraxia; were admitted to any location other than the surgical intensive care unit; or had positive blood cultures were excluded. SAS 9.4 was used to conduct statistical analysis.@*RESULTS@#Over the 9-year study period, 35 patients were admitted to the surgical intensive care unit with a verified SCI. Seven patients experienced maximum temperatures of ≥ 40 ℃. Six of those patients were treated with the dry water temperature management system with an overall mortality of 57.1% in this subgroup. The mortality rate for the 28 patients who experienced a maximum temperature of ≤ 40 ℃ was 21.4% (p = 0.16).@*CONCLUSION@#The diagnosis of quad fever should be considered in patients with cervical SCI in the presence of hyperthermia. In this study, there was no significant difference in mortality between quad fever patients treated with a dry water temperature management system versus SCI patients without quad fever. The early use of a dry water temperature management system appears to decrease the mortality rate of quad fever.

Clinical efficacy and influencing factors of mild therapeutic hypothermia for influenza-associated encephalopathy/encephalitis in children with different center temperatures / 中国热带医学

@#Abstract: Objective To investigate the clinical outcomes and influencing factors of mild therapeutic hypothermia for influenza-associated encephalopathy/encephalitis (IAE) in children with different center temperatures, and to provide ideas and references for new mild therapeutic hypothermia scheme. Methods　A total of 115 hospitalized children with IAE who were scheduled to receive mild therapeutic hypothermia in Zhongshan Hospital Affiliated to Xiamen University from January 2019 to February 2022 were collected as subjects. They were randomly divided into two groups, namely, the 33 ℃ group (n=60) and the 35 ℃ group (n=55). The clinical features and clinical outcomes of the two groups were analyzed. Univariate and multivariate logistic regression analysis was performed for 6-month to investigate the factors affecting neurological disability. Results　The baseline indicators after treatment, such as Glasgow Coma Scale (GCS) score, cerebrospinal fluid total protein (CSF-TP), CSF lactate dehydrogenase (CSF-LDH), lymphocyte (Lym), creatine kinase-MB (CK-MB), LDH, and neuron-specific enolase (NSE), revealed no significant differences between the two groups before treatment or after treatment (P>0.05). There was no significant difference between the two groups after treatment in the clinical outcomes including GCS score D-value, time of hospitalization, 6-month neurological disability rate and mRS score, CSF-TP D-value, CSF-LDH D-value, Lym D-value, CK-MB D-value, LDH D-value, NSE D-value, improvement rate of EEG and MRI (P>0.05). Univariate and multivariate logistic regression analyses [OR=1.185, 95%CI (1.026~1.369), P=0.021] indicated that the delay of the onset of mild therapeutic hypothermia treatment was an independent risk factor for neurological disability in children with IAE after mild therapeutic hypothermia treatment of 6 months. Conclusion　There was no significant difference in the clinical outcomes between 33 ℃ and 35 ℃ mild therapeutic hypothermia for children with IAE. Therefore, mild therapeutic hypothermia for children with IAE may not require a strict requirement. Timely receipt of mild therapeutic hypothermia is a key measrue to reduce the risk of neurological disability in children with IAE.

Newer Therapies In Management of Neonatal Birth Asphyxia

Asphyxia is an insult to the fetus or newborn due to lack 1 of oxygen or lack of perfusion to various organs.National Neonatology Forum of India has de?ned asphyxia as gasping or ineffective breathing or lack of 2breathing at 1 min of life.Birth asphyxia is one of the most important causes of neonatal brain injury whose incidence ranges from 3.7 to 9/1000 deliveries in the 3west.With the advent of therapeutic hypothermia (TH), improved outcomes are being reported in moderate HIE. TH, however, has not demonstrated improvement in outcomes related to severe HIE. . This has led clinicians and researchers to continue evaluating complementary and/or alternative therapies for infants with HIE. In this review, we will discuss current and emerging therapies in the management of HIE, other than hypothermia. With issues of access to health care and the burden of birth asphyxia shifting to developing and least developed nations, there is a need for alternative and supplementary neuroprotective agents. Low cost and easy availability along with ease of use would assist in ensuring that these therapies have global applicability. So global efforts must be taken to increase such studies as birth asphyxia is causing more morbidity & mortality globally

Research progress of neuroregeneration and multimodal neuromodulation in the treatment of spinal cord injury / 中国综合临床

Spinal cord injury has a high rate of disability in clinical practice, which can be divided into complete SCI and incomplete SCI according to different injury segments and severity.The main purpose of treatment is to protect the nerves.At present, acute spinal cord injury is mainly treated with surgical decompression, neurotrophic treatment, hormone therapy, hypothermia therapy, rehabilitation intervention and other clinical comprehensive treatment.In recent years, breakthroughs have been made in the field of endogenous and exogenous neural stem cell research, and important progress has been made in the basic research of stem cell transplantation.In the long run, nerve regeneration and nerve modulation may be the most promising therapy for the repair of spinal cord injury.

Targeted temperature management of severe traumatic brain injury in children / 中国小儿急救医学

Traumatic brain injury(TBI) is one of leading causes of death and disability in children.Targeted temperature management(TTM) may reduce unfavorable outcomes of TBI patients, and many studies have made much effort for developing a norm in managing temperature in TBI patients.TTM, including therapeutic hypothermia, has been recognized as one of candidate methods of neuroprotective treatment.However, the efficacy of hypothermia for patients with severe TBI is not clear.In this article, we will review studies on the potential effects of hypothermia, discuss the possible pathophysiology of neuroprotection with therapeutic hypothermia in PICU, and explore the role of TTM in pediatric severe TBI.

Effects of therapeutic hypothermia on myocardial Ca2+/calmodulin-dependent protein kinase Ⅱ and autophagy after cardiopulmonary resuscitation in swine / 中华急诊医学杂志

Objective To investigate the effects of therapeutic hypothermia (TH) on myocardial Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) and cell autophagy after cardiopulmonary resuscitation (CPR) in swine.Methods Twenty healthy male domestic swine weighing 33-40 kg were randomly (random number) divided into 3 groups:sham group (n=4),CPR group (n=8) and TH group (n=8).Sham animals only underwent general preparation without experiencing cardiac arrest and resuscitation.The animal model was established by 8 min of electrically induced ventricular fibrillation and then 5 min CPR in the CPR and TH groups.Successful resuscitation was regarded as an organized rhythm with a mean arterial pressure of greater than 50 mmHg for 5 min or more.After successful resuscitation,body temperature was decreased to 33 ℃ by a cooling blanket and then maintained until 24 h post-resuscitation,and followed by a rewarming at a rate of 1 ℃/h for 5 h in the TH group.A normal temperature was maintained by the blanket throughout the experiment in the sham and CPR groups.At 6,12,24 and 30 h after resuscitation,the values of stroke volume (SV) and global ejection fraction (GEF) were measured by PiCCO,and meanwhile the serum concentrations of cardiac troponin Ⅰ (cTnI) were measured by ELISA assay and the serum activities of creatine kinase-MB (CK-MB) were evaluated by an automatic biochemical analyzer.At 30 h after resuscitation,the animals were sacrificed and left ventricular myocardium was obtained for the determination ofCaMK Ⅱ,microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ) and p62 expressions by Western blot.The variables were compared with One way analysis of variance and then the Bonferroni test among the three groups.Results Compared with the sham group,myocardial dysfunction and injury after resuscitation were observed in the CPR and TH groups,which were indicated by decreased SV and GEF and also increased cTnI concentration and CK-MB activity in serum (all P＜0.05).Compared with the CPR group,the values of SV and GEF were significantly increased at 6 h after resuscitation,and serum cTnI concentration and CK-MB activity were significantly decreased starting 12 h after resuscitation in the TH group [SV (mL):25.0±6.9 vs 31.9±3.3 at 6 h,26.7±5.1 vs 34.6±3.7 at 12 h,28.8±3.3 vs 35.7±3.2 at 24 h,29.2±5.2 vs 36.7±3.3 at 30 h;GEF (％):17.1±2.7 vs 19.9±1.8 at 6 h,18.7±1.9 vs 21.6±1.8 at 12 h,19.3±2.3 vs 23.0±2.4 at 24 h,21.0±1.7 vs 23.7±1.7 at 30 h;cTnI (pg/mL):564±51 vs 466±56 at 12 h,534±38 vs 427±60 at 24 h,476±55 vs 375±46 at 30 h;CK-MB (U/L):803±164 vs 652±76 at 12 h,693±96 vs 557±54 at 24 h,633±91 vs 480±77 at 30 h,all P＜0.05].Tissue detection indicated that the expression of CaMK Ⅱ and LC3 Ⅱ were increased while the expression of p62 was decreased in post-resuscitation myocardium in the CPR and TH groups compared with the sham group (all P＜0.05).However,the expression of CaMK Ⅱ and LC3 Ⅱ were decreased and the expression of p62 was increased in postresuscitation myocardium in the TH group compared to the CPR group (CaMK Ⅱ:0.73±0.06 vs 0.58±0.05;LC3 Ⅱ:0.69±0.09 vs 0.50±0.07;p62:0.40±0.07 vs 0.68±0.14,all P＜0.05).Conclusion The mechanism of TH alleviating post-resuscitation myocardial dysfunction and injury may be related to the inhibition of CaMK Ⅱ expression and cell autophagy.

Mild hypothermia combined with intravenous thrombolytic therapy can improve cognitive functioning and stress response after cerebral infarction / 中华物理医学与康复杂志

Objective To explore the effect of combining mild hypothermia with intravenous thrombolytic therapy on the cognitive functioning and stress response of persons with acute cerebral infarction.Methods A total of 126 patients with acute cerebral infarction were randomly divided into a control group,a study group 1 and a study group 2,each of 42.All three groups were given intravenous thrombolytic therapy,while study group 1 also received 12 hours of mild hypothermia,and study group 2 received 24 hours.Before the treatment and 1,7,14,30 and 90 days later the National Institutes of Health stroke scale (NIHSS) was used to evaluate the subjects' nerve functions.Intracranial pressure,oxidative stress,and inflammatory cytokine levels were also measured before the treatment and 2,3 and 7 days afterward.Results The average NIHSS scores of both study groups were significantly lower than that of the control group at each time point after the treatment.Study group 2 showed significantly greater improvement than study group 1.The total effectiveness rate was 76.2％ in study group 1 and 85.7％ in study group 2,both significantly better than in the control group but without significant difference between the study groups.Both study groups' average intracranial pressures were significantly lower than the control group's average after the treatment.Moreover,3 and 7 days after the treatment,the average intracranial pressure of study group 2 was significantly lower than study group 1's average.After 1,3 and 7 days,significant differences in superoxide dismutase and malondialdehyde levels were observed between the study groups and the control group.Three days after the treatment,the average TNF-α,IL-1β and IL-6 levels of the study groups were significantly lower than the control group's average,and those of study group 2 were significantly lower than those of study group 1.The total incidence of adverse reactions was not significantly different among the 3 groups.Conclusion For patients with acute cerebral infarction,thrombolytic therapy combined with mild hypothermia for 24 hours has a definite curative effect.It can improve intracranial pressure,reduce oxidation and inflammation and improve neurological function.The patients recover well.The combined therapy is safe and worthy of clinical application.

Therapeutic hypothermia reduced brain damage on rats after cardiopulmonary resuscitation by activating Ⅲ-type PI3K pathway to increase autophagy / 中华危重病急救医学

Objective To investigate the effect of Ⅲ-type phosphatidylinositide 3 kinase (PI3K) pathway adjusting autophagy on brain damage mechanism after cardiopulmonary resuscitation (CPR) and hypothermia treatment.Methods The asphyxia induce cardiac arrest-CPR model was reproduced on healthy male Sprague-Dawley (SD) rats.Sixty rats after restoration of spontaneous circulation (ROSC) were randomly divided into normothermia group,therapeutic hypothermia group and PI3K inhibitor 3-methyl adenine (3-MA) pretreatment group,differentiated by 24 hours and 48 hours after ROSC.Each group had 10 rats at each time point.The anal temperature in the normothermia group was maintained at (37.0 ± 0.2) ℃,and the rats in the hypothermia group were given cooling treatment immediately after ROSC,and the target rectal temperature was 32-34 ℃.In the 3-MA pretreatment group,10 mmol/L 3-MA 5 μL was injected into the ventricle 20 minutes before asphyxia,and other groups were given the same amount of normal saline.Ten rats without CPR were included in Sham group only received anesthesia and catheterization.The rats were sacrificed at 24 hours and 48 hours after ROSC respectively,and the brain tissues were harvested,the brain water content (BWC) was measured by dry-wet weight method.Western Blot was used to determine the autophagy related proteins Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3),apoptosis related proteins Bcl-2 and caspase-3,and the Ⅲ-type PI3K pathway proteins Vps34 and Atgl4.Ultrastructural changes in brain tissue were observed with transmission electron microscope.Neurological deficit scores (NDS) was obtained in each group at 48 hours after ROSC.Results Compared with Sham group,the cortex at 24 hours after ROSC in normothermic group showed obvious edema,apeptosis and autophagy began to appear under transmission electron microscope,and the expressions of autophagy,apoptosis and Ⅲ-type PI3K-related proteins in brain tissue were significantly increased in a time-dependent manner,and the neurological function at 48 hours after ROSC was significantly damaged.After hypothermia intervention,brain edema of rats was significantly reduced,no obvious apoptosis was found,but autophagy was increased,the expressions of autophagy-related proteins Vps34,Atg14 and Ⅲ-type PI3K-related proteins Beclin-1 and LC3 at 48 hours after ROSC were further higher than those of normothermic group (Vps34/GAPDH:0.25±0.03 vs.0.15±0.04,Atg14/GAPDH:0.12±0.03 vs.0.05±0.04,Beclin-1/GAPDH:0.060±0.002 vs.0.018±0.002,LC3-Ⅱ/GAPDH:0.160±0.010 vs.0.050± 0.010,all P ＜ 0.05),the expressions of apoptosis related proteins Bcl-2 and caspase-3 were significantly lowered (Bcl-2/GAPDH:0.05±0.03 vs.0.20±0.04,caspase-3/GAPDH:0.050±0.002 vs.0.140±0.015,both P ＜ 0.05),neurological function was significantly improved (NDS:157±85 vs.343± 198,P ＜ 0.05).Pretreatment with 3-MA inhibited the protective effect of hypothermia on brain tissues.The expressions of Vps34,Atg14,Beclin-1 and LC3 in brain tissues at 48 hours after ROSC in 3-MA pretreatment group was significantly lower than those in the hypothennia group (Vps34/GAPDH:0.18±0.03 vs.0.25±0.03,Atg44/GAPDH:0.07±0.04 vs.0.12±0.03,Beclin-1/GAPDH:0.015±0.003 vs.0.060±0.002,LC3-Ⅱ/GAPDH:0.045±0.030 vs.0.160±0.010,all P ＜ 0.05),the expressions of Bcl-2 and caspase-3 were significantly increased (Bcl-2/GAPDH:0.15±0.04 vs.0.05±0.03,caspase-3/GAPDH:0.120±0.015 vs.0.050±0.002,both P ＜ 0.05),and NDS score was significantly increased (341±208 vs.157±85,P ＜ 0.05).Conclusion Hypothermia treatment reduced brain edema and ameliorated brain function after CPR,which might be related to increase autophagy and inhibit apoptosis adjustment by activating Ⅲ-type PI3K pathway.

Hipotermia terapéutica controlada. Experiencia en un Hospital de Tercer Nivel / Therapeutic hypothermia. Experience in a Third Level Hospital / Hipotermia terapêutica controlada experiência em um hospital de alta complexidade

Resumen: Objetivo: Presentar la experiencia relacionada a hipotermia terapéutica controlada en pacientes graves que presentaron lesión neurológica aguda. Material y métodos: Estudio clínico, retrospectivo, observacional y descriptivo, en el Departamento de Medicina Crítica de Adultos de un Hospital de Tercer Nivel en un periodo comprendido del 01 de enero de 2016 al 31 de julio de 2017. Pacientes llevados a hipotermia terapéutica. Resultados: Cinco pacientes incluidos en el estudio, con una media de edad de 52.4 años, 80% con padecimientos neurocríticos. El promedio de estancia en la UCI fue de 15.2 días, y de hospitalización 63 días. La media de días de ventilación mecánica fue de 13.8 días. Sesenta porciento de los pacientes desarrolló neumonía asociada a la ventilación mecánica. Cuarenta porciento de los pacientes presentó una discapacidad grave. Conclusiones: La hipotermia terapéutica en el grupo estudiado no impactó de manera positiva en los desenlaces neurológicos. La complicación más frecuente fue la neumonía asociada a la ventilación mecánica.

Abstract: Objective: To present the experience related to controlled therapeutic hypothermia in severe patients who presented acute neurological injury. Material and methods: Clinical, retrospective, observational and descriptive study in the Department of Critical Care of Adults of a Hospital of Third Level in a period between January 1, 2016 and July 31, 2017. Patients taken to therapeutic hypothermia. Results: Five patients included in the study, with a mean age of 52.4 years, 80% with neurocritical conditions. The average stay in the ICU was 15.2 days, and hospitalization was 63 days. The mean number of days of mechanical ventilation was 13.8 days. Sixty percent of patients developed ventilator-associated pneumonia. Forty percent of the patients had a severe disability. Conclusions: Therapeutic hypothermia in the study group did not positively impact neurological outcomes. The most frequent complication was ventilator-associated pneumonia.

Resumo: Objetivo: Apresentar a experiência relacionada à hipotermia terapêutica controlada em pacientes graves que apresentaram lesão neurológica aguda. Material e métodos: Estudo clínico, retrospectivo, observacional e descritivo, no Departamento de Medicina Crítica de adultos, no período de 1 de janeiro de 2016 a 31 de julho de 2017. Pacientes submetidos à Hipotermia Terapêutica. Resultados: Foram incluídos no estudo 5 pacientes com idade média de 52.4 anos, 80% com alterações neurológicas. A permanência média na UTI foi de 15.2 dias e de hospitalização 63 dias. A média de dias de ventilação mecânica foi de 13.8. 60% dos pacientes desenvolveram pneumonia associada à ventilação mecânica. 40% dos pacientes tinham um incapacidade grave. Conclusões: A hipotermia terapêutica no grupo estudado não teve impacto positivo nos desfechos neurológicos. A complicação mais frequente foi pneumonia associada à ventilação mecânica.

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy / Eficácia da hipotermia passiva e eventos adversos durante o transporte de recém-nascidos asfixiados de acordo com a gravidade da encefalopatia hipóxico-isquêmica

Abstract Objective To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. Methods This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Results Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4 ± 1.4 °C and mean transfer time was 3.3 ± 2.0 h. Mean age at arrival was 5.6 ± 2.5 h. Temperature at arrival was between 33 and 35 °C in 41 (61%) infants, between 35 °C and 36.5 °C in 15 (22%) and <33 °C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature < 33 °C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p < 0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. Conclusion The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport.

Resumo Objetivo Determinar se a eficácia da hipotermia passiva e eventos adversos durante o transporte estão relacionados à gravidade da encefalopatia hipóxico-isquêmica neonatal. Métodos Estudo retrospectivo de 67 neonatos com encefalopatia hipóxico-isquêmica (nascidos entre abril de 2009 e dezembro de 2013) transferidos para hipotermia terapêutica e resfriados durante o transporte. Resultados Foram transportados 56 recém-nascidos (84%) sem fontes externas de calor e 11 (16%) precisaram de uma fonte externa de calor. A temperatura média na saída foi de 34,4 ± 1,4 °C e o tempo médio de transporte foi de 3,3 ± 2,0 horas. A idade média na chegada foi de 5,6 ± 2,5 horas. A temperatura na chegada ficou entre 33-35 °C em 41 (61%) neonatos, entre 35°-36,5 °C em 15 (22%) e < 33 °C em 11 (16%). Neonatos com encefalopatia hipóxico-isquêmica grave apresentaram maior risco de temperatura < 33 °C na internação (RC 4,5; IC de 95% 1,1-19,3). A gravidade da encefalopatia hipóxico-isquêmica e o pH da artéria umbilical foram fatores de risco independentes para uma baixa temperatura na internação (p < 0,05). Eventos adversos durante o transporte, principalmente hipotensão e sangramento do tubo endotraqueal, ocorreram em 14 neonatos (21%), sem diferenças entre neonatos com encefalopatia hipóxico-isquêmica moderada ou grave. Conclusão O risco de super-resfriamento durante o transporte é maior em recém-nascidos com encefalopatia hipóxico-isquêmica grave e naqueles com acidose mais grave no nascimento. Os eventos adversos mais comuns durante o transporte estão relacionados a deterioração fisiológica e sangramento do tubo endotraqueal. Essa observação fornece informações úteis para identificar neonatos asfixiados que exigem maior vigilância clínica durante o transporte.

An interpretation of an evidence-based guideline from the American Neuro-critical Care Society about the implementation of targeted temperature management / 中华危重病急救医学

Objective Targeted temperature management (TTM) is often used in neuro-critical care to minimize secondary neurologic injury and improve outcomes. Evidence-based implementation guideline of TTM was generated from clinical questions relevant to TTM implementation for neuro-critical care by experts recruited by the American Neuro-critical Care Society. Interpretation of this guideline would help the readers to understand the implementation of TTM, bring benefits to standardization of TTM application, and contribute to the solving of specific issues related to TTM implementation.

The effects of rapid hypothermia induced via esophagus on intestinal mucous injury in early stage after cardiopulmonary resuscitation in a swine model of cardiac arrest / 中华急诊医学杂志

Objective To investigate the effects of rapid hypothermia induced via esophagus on intestinal mucous injury in early stage after cardiopulmonary resuscitation (CPR) in a swine model of cardiac arrest.Methods Twenty-seven male domestic pigs weighing (36±2)kg were utilized.The animals were randomly crandom number divided into 3 groups (n=9 in each):normothermia group (NT group),surface cooling group (SC group),and esophageal cooling group (EC group).The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of CPR.At 5 mins after restoration of spontaneous circulation (ROSC),therapeutic hypothermia was applied by either an esophageal cooling device in the EC group or a surface cooling blanket in the SC group to reach a targeted temperature of 33 ℃ maintained for 24 h after ROSC,and then followed by warming up in a rate of 1 ℃ / hr for 5 hrs.A normal temperature of (38.0±0.5)℃ was maintained throughout the experiment in the NT group.The core temperature was continuously monitored during a period of 30 h after ROSC.At 3 h,6 h,12 h,24 h and 30 h after ROSC,intestinal fatty acid binding protein (IFABP) content and diamine oxidase (DAO) activity in serum were measured by ELISA.At 30 h after ROSC,the pigs were sacrificed,and then intestinal tissue was rapidly obtained for the determination of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents by ELISA,cell apoptosis by TUNEL,and caspase-3 expression by immunohistochemistry.Results The rate of temperature decrease was 2.8 ℃/h and the time required for target temperature was 102 min in the EC group,while the rate of temperature decrease was 1.5 /h and the time consumed for target temperature was 185 mins in the SC group,which suggested the efficacy of cooling was significantly better in the EC group than that in the SC group (both P＜0.05).Compared with the NT group,serum IFABP content and DAO activity were significantly decreased at 3 hrs after ROSC in the EC group and at 6 hrs after ROSC in the SC group.Compared with the SC group,serum IFABP content at 6 hrs after ROSC and DAO activity at 12 h after ROSC were significantly decreased in the EC group IFABP (pg/mL):(710±32) vs.(777±52) at 6 h,(870±49) vs.(960±64) at 12 h,(1 022±65)vs.(1 143±63) at 24 h,(882±71) vs.(1 006±45) at 30 h DAO (U/mL):(39.9±1.9) vs.(43.4±3.2) at 12 h,(30.6±2.4) vs.(34.0±3.1) at 24 h,(26.1±2.7) vs.(29.4±2.2) at 30 h,all P＜0.05.In the intestinal tissue,TNF-α and IL-6 contents were significantly reduced,and cell apoptosis index and caspase-3 expression were significantly decreased in the SC and EC groups compared with the NT group.Additionally,inflammatory response and cell apoptosis in intestinal tissue were further significantly lesser in the EC group compared with the SC group TNF-α (pg/mL):(721±94) vs.(922±125);IL-6(pg/mL):(454±69) vs.(697±132);Apoptotic index(％):(6.2±2.6)vs.(12.8±3.0);caspase-3 expression (IOD):(8.9±1.6) vs.(15.9±1.9),all P＜0.05.Conclusions In a swine model of cardiac arrest,rapid hypothermia could be successfully induced via esophagus and consequently produced a greater protective effect on post-resuscitation intestinal injury compared with the conventional surface cooling.The protective mechanisms are associated with the inhibition of inflammatory response and cell apoptosis.

Effect of different therapeutic time windows of mild hypothermia on neurological protection from ventricular fibrillation in rabbit models / 中华急诊医学杂志

Objective To investigate the effects of mild hypothermia on post-resuscitation neurological outcome after ventricular fibrillation (VF) in rabbits.Methods Forty-five adult New Zealand rabbits were induced VF by direct current of electricity.The rabbits were randomly(random number) divided into following groups:normothermic resuscitation group (NR),mild hypothermia prearrest group (HP),mild hypothermia resuscitation 30 min group (HRe30),mild hypothermia resuscitation 90 min group (HRe90),normothermic sham group (NS),and hypothermia sham group (HS).The rabbits of NR group were observed for 600 min in room temperature after restoration of spontaneous circulation (ROSC).The mild hypothermia was induced by surface cooling,and maintained for 600 min after the aimed low temperature reached.The arterial blood samples were collected for determining neuron-specific enolase (NSE) and thioredoxin (Trx) and the mean arterial pressure (MAP),left ventricular end-diastolic pressure (LVEDP) and left ventricular pressure raise and fall rate (±dp/dtmax) were observed at 15 min before CA,and 30 min,60 min,120 min,360 min and 600 min after ROSC.After the animals were sacrificed at 600 min after ROSC,the whole brain of animals was harvested and observed under light microscope to calculate the apoptotic index of the hippocampal CA1 neurons by using TUNEL method.One-way ANOVA was used to determine the statistical significance between two groups,a two-tailed value of P＜0.05 was considered statistically significant.Results (1) Hemodynamically compared with normal temperature groups,HR was lower in hypothermia groups.Compared with NR,HRe30,and HRe90 group,LVEDP was higher in HP group at 30 min after ROSC(3.4±0.8 vs.4.6±1.0,4.1±0.5,4.3±0.2,F=9.85,P=0.019).In Hp group,the level of +dp/dtmax was higher than that in NR,HRe30 and HRe90 groups at 30 min and 120 min after ROSC.In HP group,the level of-dp/dtmax was higher than that of NR group at 30 min,60 min,120 min,360 min and 600 min after ROSC.(2) Serologically compared with HP,HRe30 and HRe90 group,NSE levels were higher in NR group at 60 min,120 min and 360 min after ROSC.Compared with NR,HRe30,and HRe90 group,Trx levels in NR group were lower at 60 min,120 min,360 min and 600 min after ROSC.Compared with HP group,Trx levels in HRe30 and HRe90 groups were higher at 60 min,120 min,360 min and 600 min after ROSC.(3) Pathologically compared with NR group,histopathological changes in hippocampus CA1 area were milder found in HP,HRe30 and HRe90 groups.AI (％) was lower in HP,HRe30 and HRe90 groups than that in NR group[(62.25±10.43)％ vs.(20.61±5.02)％,(25.08±3.92)％,(30.33±7.15)％,P=0.001].Concusions This study shows that hypothermia should be initiated as soon as possible,and especially early intra-arrest cooling appears to be significantly better than post-ROSC cooling and normothermia.

Clinical managements of therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy / 中华实用儿科临床杂志

Therapeutic hypothermia is believed to improve neurodevelopment outcome of infants with moderate-to-severe hypoxic-ischemic encephalopathy(HIE),however,the severe brain injury and neurologic sequelae still can be observed in some infants received therapeutic hypothermia.Optimal monitor and management of systematic complications presented by infants during cooling treatment are necessary for improvement of overall outcome.Therefore,it is essential to understand the functional change of each system of the whole body,to adapt adequate diagnostic methods and to train multidisciplinary staffs to monitor and manage moderate-to-severe HIE infants during therapeutic cooling.With the development of therapeutic hypothermia,it is currently considered as a standard of care for infants with moderate-to-severe HIE.It is recommended that any neonatal intensive care unit(NICU) using routinely therapeutic hypothermia to reference the national or international benchmarking protocols in order to improve the medical quality and prognosis of infants.

The molecular mechanisms of hypothermia cerebral protection / 天津医药

Therapeutic hypothermia (TH), also known as targeted temperature management (TTM), is the intentional reduction of core body temperature to 32-35℃. Mild-to-moderate hypothermia and advanced cooling technology can be used as an effective component of multimodal therapy for ischemic encephalopathy, brain trauma, haemorrhagic stroke, or other forms of severe brain injury and acute neurological injuries to achieve neuroprotection. The events occured after an episode of acute neurological injuries and cerebral ischemia are multiple. And the possible explanation for the neuroprotective benefits of hypothermia therapy is inhibiting metabolic disruption, excitotoxicity, oxidative stress, cell apoptosis signals, inflammatory responses, and promoting neuronal integrity and blood-brain barrier integrity. To know the molecular mechanisms of action of TH, which exerts neuroprotective function, will provide clinicians a better understanding the indications and contraindications of this therapy, and provide a possible theoretical reserves and clinical practice for other therapies when used in conjunction with hypothermia.

Application of amplitude integrated electroencephalography in the therapeutic hypothermia of hypoxic-ischemic encephalopathy / 中华实用儿科临床杂志

Hypoxic-ischemic encephalopathy (HIE) is the main reason of causing neonatal death and poor prognosis of the nervous system.The treatment of HIE has gone into the era of therapeutic hypothermia,the early,continuous,specification amplitude integrated electroencephalography(aEEG) monitoring for therapeutic hypothermia to screen appropriate cases,assess early the severity of HIE,provide early nerve protection treatment and evaluate the therapeutic efficiency,early intervention and improve the prognosis of the long-term HIE.This paper review the application of aEEG in the therapeutic hypothermia of HIE.

Effect of hypothermia status in donors on renal graft function after renal transplantation from donation after citizen's death / 器官移植

Objective To evaluate the effect of hypothermia status in the donors upon the renal graft function after renal transplantation from donation after citizen's death. Methods Thirty-six eligible donors were randomly divided into the normal temperature (body temperature 36.5-37.5 ℃ , n=19) and hypothermia groups (body temperature 34.0-35.0 ℃ , n=17). The matched recipients undergoing renal transplantation were also assigned into the normal temperature (n=38) and hypothermia groups (n=34). Perioperative conditions of the donors and recipients were compared between two groups. And postoperative renal graft function of the recipients were statistically compared between two groups, including the incidence of delayed graft function (DGF) and primary nonfunction (PNF). Results No statistical significance was identified in the perioperative amount of urine volume, serum creatinine (Scr), systolic blood pressure, saturation oxygen, warm ischemia time and cold ischemia time of the donors between two groups (all P>0.05). No statistical significance was noted in terms of the operation time, intraoperative mean blood glucose and intraoperative mean arterial pressure of the recipients between two groups (all P>0.05). Postoperative incidence of DGF of the recipients in the hypothermia group was 6%, significantly lower than that in the normal temperature group (24%) (χ2=4.393, P=0.036). Postoperative incidence of PNF of the recipients was 3% in both the hypothermia and normal temperature groups with no statistical significance (χ2=0.000, P=1). Conclusions The hypothermia status of the donors can significantly reduce the incidence of DGF, whereas exerts no evident effect upon the incidence of PNF in the recipients.

Neuroprotective effect of therapeutic hypothermia induced by dihydrocapsaicin on cerebral ischemia reperfusion injury in mice / 新乡医学院学报

Objective To investigate the neuroprotective effect and its mechanism of therapeutic hypothermia induced by dihydrocapsaicin (DHC) on cerebral ischemia reperfusion injury in mice.Methods Twenty adult wild type (WT) mice were randomly divided into WT group and WT + DHC group,ten mice in each group.Twenty transient receptor potential receptor 1 (TRPV1) knockout mice were randomly divided into TRPV1 KO group and TRPV1 KO + DHC group,ten mice in each group.The model of focal cerebral ischemia reperfusion injury was established in all mice.The mice in the WT group and TRPV1 KO group were subcutaneously injected with physiological saline 1.25 mg · kg-1 · h-1 after reperfusion.The mice in the WT + DHC group and TRPV1 KO + DHC group were subcutaneously injected with DHC 1.25 mg · kg-1 · h-1 after reperfusion.All the mice were moved into the cage at 22 degrees centigrade after 90 minutes of reperfusion.The core body temperature during the reperfusion period was recorded in every 5 minutes to 24 hours after reperfusion.The neurobehavioral score was performed before anesthesia and 24 hours after anesthesia.After the neurobehavioral test,the brain tissue sections of mice were stained with 2,3,5-triphenyltetrazolium chloride;and the infarction rate of the brain tissue was calculated.Results There was no significant difference in the core body temperature among the four groups at 0,30 and 60 minutes after reperfusion (P ＞ 0.05).There was no significant difference in the core body temperature between 90 minutes and 0,30 and 60 minutes after reperfusion (P ＞ 0.05);but the core body temperature at 2,3,4,6,12 and 24 hours after reperfusion was significantly lower than that at 0,30,60 and 90 minutes after reperfusion in WT group,TRPV1 KO group and TRPV1 KO + DHC group(P ＜ 0.05).There was no significant difference in the core body temperature among the WT group,TRPV1 KO group and TRPV1 KO + DHC group at 2,3,4,6,12 and 24 hours after reperfusion (P ＞ 0.05).The core body temperature at 90 minutes and 2,3,4,6,12,24 hours after reperfusion was significantly lower than that at 0,30 and 60 minutes after reperfusion in WT + DHC group(P ＜ 0.05);and the core body temperature in WT + DHC group was significantly lower than that in WT group,TRPV1 KO group and TRPV1 KO + DHC group at the same time point(P ＜ 0.05).There was no significant difference in the total neurobehavioral score among the four groups before anesthesia (P ＞ 0.05).The total neurobehavioral score at 24 hours after reperfusion was significantly lower than that before anesthesia in the four groups (P ＜ 0.05).The total neurobehavioral score in WT + DHC group was significantly higher than that in WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion(P ＜0.05).There was no significant difference in the total neurobehavioral score among WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion (P ＞ 0.05).There was no significant difference in the score of spontaneous activity,climbing test,body proprioception and response to vibrissae touch among the four groups at 24 hours after reperfusion (P ＞ 0.05).The score of symmetry test of limbs movement and forepaw stretching test in WT + DHC group was significantly higher than that in WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion(P ＜ 0.05).There was no significant difference in the score of symmetry test of limbs movement and forepaw stretching test among the WT group,TRPV1 KO group and TRPV1 KO + DHC group at 24 hours after reperfusion (P ＞ 0.05).The infarction rate of brain tissue in WT + DHC group was significantly lower than that in the other three groups at 24 hours after reperfusion (P ＜ 0.05);but there was no significant difference in the infarction rate of brain tissue among the WT group,TRPV1 KO group and TRPV1 KO + DHC group (P ＞ 0.05).Conclusion Subcutaneous injection of DHC after focal cerebral ischemia and repeffusion of mice can induce therapeutic hypothermia by activating TRPV1 receptor,and reduce brain tissue damage and improve neurological function.