Mild Hypothermia Treatment Group Research Articles

The Diagnostic Value of Cystatin C and Mild Hypothermia Therapy Based on Immunoturbidimetry Enhanced by Nanospheres in Asphyxia Neonate

In order to evaluate the early diagnosis value of CysC and the influence of mild hypothermia on the renal damage of asphyxia neonates, the serum cystatin C (CysC) levels of asphyxia neonates and normal neonates were measured by the nanomicrosphere-enhanced immunoturbidimetric method. The treatment was carried out, and the influence of mild hypothermia treatment on the renal damage of asphyxia neonates was analyzed. The results showed that the indicators of the asphyxia group were significantly higher than those of the control group, and the severe asphyxia group was significantly higher than that of the mild asphyxia group, which was statistically significant p < 0.05 ; the heart rate of patients in the mild hypothermia treatment group decreased gradually with the decrease in body temperature. And compared with the control group, there was a significant difference ( p < 0.05 ); after symptomatic treatment, the two groups of ALT, AST, BUN, and SCR were improved to varying degrees, and the difference was statistically significant compared with before treatment ( p < 0.05 ). Studies have shown that serum CysC level can be used as an indicator to detect glomerular filtration function and early asphyxia newborns, and it is sensitive and specific for early diagnosis of kidney damage. At the same time, it can be used to monitor clinical renal function and determine the status of asphyxia newborns.

Effect of long-term and short-term mild hypothermia in severe traumatic brain injury: a comparative study

To explore the effects of different mild hypothermia therapy time on the efficacy and complications of patients with severe traumatic brain injury (STBI). A retrospective research method was used. 132 patients with STBI given mild hypothermia therapy admitted to the Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine from January 2010 to December 2018 were enrolled. According to the days of mild hypothermia therapy, the patients were divided into 2-day mild hypothermia treatment group, 5-day mild hypothermia treatment group and 14-day mild hypothermia treatment group. Glasgow coma score (GCS) after treatment of 10 days and 30 days, 30-day disability rate and mortality, coma time, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-dimer, and the incidence of complications such as decreased blood pressure, decreased gastrointestinal motility, infection, nonunion of scalp, cerebrospinal fluid leakage, etc. were compared among three groups. Among the 132 patients with STBI, there were 44 cases in the 2-day mild hypothermia treatment group, 45 cases in 5-day mild hypothermia treatment group, and 43 cases in 14-day mild hypothermia treatment group. There was no significant difference in gender, age, GCS score before treatment or time from injury to admission among three groups. Compared with 2-day mild hypothermia treatment group, the GCS score 10 days and 30 days after treatment in 5-day mild hypothermia treatment group and 14-day mild hypothermia treatment group were significantly higher (11.61±2.23, 10.17±2.03 vs. 6.79±1.49; 13.15±2.53, 11.24±2.24 vs. 8.79±1.59), the coma time were shorten (days: 5.79±1.89, 5.45±1.72 vs. 13.65±2.73), and 30-day disability rate and mortality were significantly decreased [13.33% (6/45), 11.63% (5/43) vs. 22.73% (10/44); 17.78% (8/45), 16.28% (7/43) vs. 31.82% (14/44)], PT and APTT were reduced obviously (s: 20.14±4.12, 22.54±3.56 vs. 30.67±5.19; 35.14±12.41, 38.59±13.54 vs. 56.67±10.62), Fib rose obviously (g/L: 1.84±0.25, 1.98±0.27 vs. 0.67±0.12), and D-dimer reduced obviously (mg/L: 53.10±19.84, 49.20±20.13 vs. 102.60±20.13), with statistically significant differences (all P < 0.05). But there was no significant difference in above indicators between the 5-day mild hypothermia treatment group and 14-day mild hypothermia treatment group (all P > 0.05). The incidence of complications in 14-day mild hypothermia group was significantly higher than those in 2-day mild hypothermia group and 5-day mild hypothermia group [decrease of blood pressure: 55.56% (20/36) vs. 36.67% (11/30), 35.14% (13/37); weakening of stomach intestinemotive power: 72.22% (26/36) vs. 46.67% (14/30), 45.95% (17/37); urethral infection: 52.78% (19/36) vs. 36.67% (11/30), 35.14% (13/37); lungs infection: 47.22% (17/36) vs. 36.67% (11/30), 37.84% (14/37); disunion of scalp: 5.56% (2/36) vs. 0% (0/30), 0% (0/37); leak of cerebrospinal fluid: 5.56% (2/36) vs. 0% (0/30), 0% (0/37), all P < 0.05], but there was no significant difference between the 2-day mild hypothermia treatment group and 5-day mild hypothermia treatment group (all P > 0.05). The optimal time frame for mild hypothermia treatment in patients with STBI is 5-day, which shortens the coma time, and reduces the mortality and the disability rate. The shorter mild temperature time cannot effectively prevent secondary brain injury. However, the prolonged period of mild temperature will affect the repair of the patient's injury tissue, which is not conducive to the recovery of patient's mechanical function and is prone to complications.

Mild hypothermia can delay the occurrence of post-stroke infection: a propensity score matched-cohort study

To evaluate the effect of mild hypothermia on the incidence of post-stroke infection and explore the relationship between mild hypothermia and outcome of stroke patients by using propensity score matching. Patients hospitalized in department of intensive care unit (ICU), neurology and neurosurgery in the First Affiliated Hospital of Guangxi Medical University due to stroke from March 2012 to April 2018 were retrospectively analyzed. According to whether or not mild hypothermia was provided, they were divided into the normal thermic group (NT group) and mild hypothermia treatment group (MHT group). The MHT group patients were matched with the NT group patients by the propensity score matching method at a ratio of 1:1. The observation period was within the first 7 days after admission. Baseline characteristics including age, gender, type of stroke, comorbidities, acute physiology and chronic health evaluation II (APACHE II) score and Glasgow coma score (GCS) on admission, surgical operation, dysphagia, invasive procedures and outcomes of these patients had been analyzed. The primary outcome was incidence of post-stroke infection, and the secondary outcomes included the time of initial infection (TII, the duration from stroke to initial infection), hospital mortality, sequential organ failure assessment (SOFA) at discharge, incidence of complications such as arrhythmia, coagulation dysfunction and multiple organ dysfunction syndrome (MODS). 201 stroke patients were enrolled, 41.8% (84/201) of whom underwent mild hypothermia. Comparison with NT group before matching, there were more males in MHT group (71.4% vs. 56.4%), the proportion of surgical operation, mechanical ventilation, deep vein catheterization and gastric catheterization were higher (78.6% vs. 54.7%, 84.5% vs. 39.3%, 90.5% vs. 37.6%, 98.8% vs. 70.9%), and so as incidence of infection (90.5% vs. 72.6%), in-hospital mortality (27.4% vs. 12.8%) and TII [hours: 62.00 (35.25, 93.00) vs. 42.00 (28.50, 69.50)]. All the differences were statistically significant (all P < 0.05). Fifty-three patients in the MHT group were matched with 53 patients in the NT group. After matching, there was no significant difference in 15 baseline characteristics between two groups. Significant differences in infection and hospital mortality between the MHT group and NT groups disappeared (92.5% vs. 88.7%, 22.6% vs. 26.4%, both P > 0.05), while TII of MHT group was longer than that of the NT group [hours: 62.00 (40.75, 92.25) vs. 40.00 (28.00, 63.00), P = 0.000]. There were no statistically significant differences in SOFA score or complications between the two groups either before or after matching. Mild hypothermia had no significant effect on the incidence of post-stroke infection and hospital mortality, it could delay the occurrence of infection and provide longer duration of treatment.

Mild hypothermia improves neurological outcome in mice after cardiopulmonary resuscitation through Silent Information Regulator 1-actviated autophagy

Mild hypothermia treatment (MHT) improves the neurological function of cardiac arrest (CA) patients, but the exact mechanisms of recovery remain unclear. Herein, we generated a CA and cardiopulmonary resuscitation (CPR) mouse model to elucidate such function. Naïve mice were randomly divided into two groups, a normothemia (NT) group, in which animals had normal body temperature, and a MHT group, in which animals had a body temperature of 33 °C (range: 32–34 °C), after the return of spontaneous circulation (ROSC), followed by CA/CPR. MHT significantly improved the survival rate of CA/CPR mice compared with NT. Mechanistically, MHT increased the expression of Silent Information Regulator 1 (Sirt1) and decreased P53 phosphorylation (p-P53) in the cortex of CA/CPR mice, which coincided with the elevated autophagic flux. However, Sirt1 deletion compromised the neuroprotection offered by MHT, indicating that Sirt1 plays an important role. Consistent with the observations obtained from in vivo work, our in vitro study utilizing cultured neurons subjected to oxygen/glucose deprivation and reperfusion (OGD/R) also indicated that Sirt1 knockdown increased OGD/R-induced neuron necrosis and apoptosis, which was accompanied by decreased autophagic flux and increased p-P53. However, the depletion of P53 did not suppress neuron death, suggesting that P53 was not critically involved in MHT-induced neuroprotection. In contrast, the application of autophagic inhibitor 3-methyladenine attenuated MHT-improved neuron survival after OGD/R, further demonstrating that increased autophagic flux significantly contributes to MHT-linked neuroprotection of CA/CRP mice. Our findings indicate that MHT improves neurological outcome of mice after CA/CPR through Sirt1-mediated activation of autophagic flux.

Mild Hypothermia Improves Neurological Outcome in Mice after Cardiopulmonary Resuscitation Through Silent Information Regulator 1-Actviated Autophagy

Mild hypothermia treatment (MHT) improves the neurological function of cardiac arrest (CA) patients, but the exact mechanisms of recovery remain unclear. Herein, we generated a CA and cardiopulmonary resuscitation (CPR) mouse model to elucidate such function. Naive mice were randomly divided into two groups, a normothemia (NT) group, in which animals had normal body temperature, and a MHT group, in which animals had a body temperate of 330C (range: 32-340C), after the return of spontaneous circulation (ROSC), followed by CA/CPR. MHT significantly improved the survival rate of CA/CPR mice compared with NT. Mechanistically, MHT increased the expression of Silent Information Regulator 1 (Sirt1) and decreased P53 phosphorylation (p-P53) in the cortex of CA/CPR mice, which coincided with the elevated autophagic flux. However, Sirt1 deletion compromised the neuroprotection offered by MHT, indicating that Sirt1 plays an important role. Consistent with the observations obtained from in vivo work, our in vitro study utilizing cultured neurons subjected to oxygen/glucose deprivation and reperfusion (OGD/R) also indicated that Sirt1 knockdown increased OGD/R-induced neuron necrosis and apoptosis, which was accompanied by decreased autophagic flux and increased p-P53. However，the depletion of P53 did not suppress neuron death, suggesting that P53 was not critically involved in MHT-induced neuroprotection. On the contrary, the application of autophagic inhibitor 3-methyladenine attenuated MHT-improved neuron survival after OGD/R, further demonstrating that increased autophagic flux significantly contributes to MHT-linked neuroprotection of CA/CRP mice. Our findings indicate that MHT improves neurological outcome of mice after CA/CPR through Sirt1-mediated activation of autophagic flux. Funding Statement: This study was supported by funding from the National Nature Science Foundation of China (81272021, 81571867), and the Fourth Batch of Youth Talent Project in the First Affiliated Hospital of Sun Yat-sen University (No.Y50152). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This project was approved by the Animal Investigation Committee of Sun Yat-sen University and the animal protocol conformed with National Institutes of Health Guidelines for ethical animal research.

Effects of mild hypothermia on autophagy in hippocampal CA1 neurons in rats after CPR

Objective To establish the cardiac arrest-cardiopulmonary resuscitation model in rats, and to observe the effect of mild hypothermia on autophagy in hippocampal CA1 neurons after ROSC. Methods A total of 36 Wistar rats were randomly divided into two groups: normal temperature treatment group(NT group) and mild hypothermia treatment group(HT group). To establish the cardiac arrest-cardiopulmonary resuscitation(CA-CPR) model in rats by epicardial electrical stimulation induced ventricular fibrillation, and to sacrifice 3 animals in each group to obtain the brain cortex in 2nd and 4th hours after ROSC in order to observe the expression of p-AMPK by electron microscope and LC3 granules through Western blot. The neurological deficit score(NDS) was assessed in 24、48、72 hours respectively after ROSC. To sacrifice the animals so as to take the cerebrum in 72 hours after ROSC, then calculate the apoptotic index of the hippocampal CA1 neurons, which were dyed through TUNEL method. Results The expression of p-AMPK、Beclin-1 and LC3-Ⅱ/LC3-Ⅰratio in Normothermia group were all lower than the Mild hypothermia group(P<0.05), the neurons plasma of hippocampal CA1 area in the Hypothermia group demonstrated obvious LC3 granules formation, the NDS score of the Normothermia group and the Mild hypothermia group in ROSC24h、ROSC48h、ROSC72h were 320vs205、285vs140、266vs120, respectively. The apoptotic index of the hippocampal CA1 area in the Normothemia group in ROSC72h was higher than the Mild hypothermia group, (P<0.05). Conclusions Mild hypothermia after cardiopulmonary resuscitation promotes autophagy of the hippocampal CA1 area neurons in rats and reduce neuronal apoptosis. Key words: Cardiac arrest; CPR; Mild hypothermia; Rat; Autophagy

Efficacy and safety of systemic mild hypothermia treatment for moderate or severe neonatal hypoxic-ischemic encephalopathy

Objective To explore the efficacy and safety of systemic mild hypothermia in management of neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). Methods A retrospective case-control study was conducted on 75 neonates with moderate or severe HIE, who were admitted to the Neonatal Intensive Care Unit of Teaching Hospital of Fujian Medical University (Quanzhou Children's Hospital) from January 1, 2011 to May 31, 2015. The 75 neonates were divided into two groups, the conventional treatment group (33 cases, control group) and the mild hypothermia treatment group (42 cases, hypothermia group). Sequential management protocol for all subjects was followed, including amplitude-integrated electroencephalogram (aEEG) before treatment, aEEG and brain MRI at one week after birth, neonatal behavioral neurological assessment (NBNA) on the 14th day after birth, and determination of mental and psychomotor development index with Bayley Scales of Infant and Toddler Developmental at 18 months old. Adverse reactions, serious disability cases and deaths during the study were also recorded. Two sample-t test and Chi-square test were as statistical methods. Results There were six death cases in the control group, but on one died in the hypothermia group. In the survivals, The maximum voltage and minimum voltage in the hypothermia group were higher at 7-day old than that before treatment [maximum voltage: (31.3±2.4) vs (18.1±2.2) μV; minimum voltage: (13.5±2.1) vs (6.1±1.5) μV, t=8.591 and 5.314, both P 0.05). Conclusions Systemic mild hypothermia treatment is effective in reducing mortality rate and major disability rate in neonates with moderate or severe HIE and improves the neuromotor development when babies grow up to 18-month-old. Key words: Hypoxia-ischemia,brain; Hypothermia, induced; Infant,newborn

Curative effect analysis of mild hypothermia in treatment of neonatal hypoxic-ischemic encephalopathy and follow-up study of 36 children aged 18 months

Objective To explore the efficacy and safety of mild hypothermia(MH) in treating the infants with moderate-to-severe neonatal hypoxic-ischemic encephalopathy(HIE), and to make a follow-up of the nerve motor development of the infants at 18 months old after discharge. Methods Totally 61 neonates with moderate-to-severe HIE in Neonatal Intensive Care Unit (NICU) from Jan.2007 to Dec.2013 were retrospectively analyzed.According to before and after MH therapeutic apparatus was used by NICU of Shanghai Children's Hospital, 61 neonates of HIE were divided into 2 groups, the conventional treatment group(25 cases) and MH treatment group(36 cases). The patients in both groups were measured respectively by using the amplitude integrated electroencephalography(aEEG) before MH treatment and at 72 hours after MH treatment, by neonatal behavioral neurological assessment(NBNA) on the 28th day after birth, and by adopting Bayley Scales of Infant Development at 18 months old.The adverse reactions, serious disability cases and deaths of MH treatment were recorded. Results Compared with the conventional treatment group, aEEG recording before treatment showed no statistically significant differences in MH treatment group[maximum voltage: (22.4±3.1) μV vs(18.6±2.5) μV, maximum voltage: (8.2±2.6)μV vs(6.5±1.9) μV, t=1.264, 0.852, all P>0.05]. However, aEEG recording at 72 h after treatment showed statistically significant differences in MH treatment group[maximum voltage: (24.1±3.2) μV vs(30.6±2.8) μV, maximum voltage: (9.7±3.4)μV vs(13.3±2.2) μV, t=6.376, 4.257, all P<0.05]. Severe disability cases[24.0%(6/25 cases)vs 5.6%(2/36 cases), χ2=4.405, P<0.05] and deaths [16.0%(4/25 cases)vs 0(0/36 case), χ2=6.164, P<0.05] in MH treatment group were significantly decreased, and there was significantly difference in NBNA on the 28th day after birth[(35.9±2.1) vs(39.1±1.6), t=3.361, P<0.05], and scales of neurobehavioral evaluation through follow-up of 18 months old [mental development index(MDI): (85.2±10.7) vs(96.5±13.1), t=7.839, P<0.05]. Very few neonates had apnea, coagulation dysfunction, arrhythmia and other adverse reactions in MH treatment course. Conclusions MH treating moderate-to-severe HIE is safe and effective.MH is effective in reducing death and major disabilities in neonates with moderate-to-severe HIE and without significant side effects.MH can obviously improve the development of nervous system disorders in 0-18 months infants, and can significantly improve these infants' Bayley developmental scale neurobehavioral scores. Key words: Mild hypothermia; Infant, newborn; Hypoxic-ischemic encephalopathy; Prognosis; Follow-up

The effect of mild hypothermia on mice cerebral ischemia-reperfusion nerve cell apoptosis

Objective To observe the treatment effect of mild hypothermia on cerebral ischemiareperfusion nerve cell apoptosis, and study its mechanism from the molecular level. Methods SD rats were employed to produce cerebral ischemia-reperfusion injury model, then were divided into mild-hypothermia treatment group and control group. The cell apoptosis was detected by TUNEL mothod, during the mild hypothermia 24 h, 48 h, 72 h, and 24 h, 48 h, 72 h, 96 h and 120 h after rewarming, and RT-PCR method was used to detect the mRNA expression apoptosis gene Caspase-3, Fas and Bcl-2 at all the above time points. Results The apoptosis cell number during mild hypothermia therapy in mild hypothermia group was less than the control group (P＜0. 05), then increased gradually after rewarming, till to 72 h there was no significant difference between two groups (P ＞ 0. 05). And the mRNA expression level of Caspase-3, Fas and Bcl-2 during mild hypothermia therapy in mild hypothermia group were lower than the control group (P ＜ 0. 05), and increased with rewarming, till to 72 h after rewarming there was no significant difference between two groups (P＞0.05). Conclusion Mild hypothermia can reduce the number of nerve cell apoptosis in the process of cerebral ischemia and reperfusion, but the apoptosis rate rise rapidly with rewarming, it suggests that nerve cells will be rescued as soon as possible during mild hypothermia. Key words: Hypothermia therapy; Apoptosis; Gene expression; Rats

Clinical study of mild hypothermia treatment of acute severe brain inyury

目的 探讨亚低温治疗急性重型颅脑损伤患者的临床疗效.方法从1998年1月至2003年6月对符合条件且GCS≤8分的重症脑外伤患者130例随机分为亚低温治疗组62例和常温治疗组68例,监测两组的颅内压、脑水肿体积和血糖,比较其治疗效果.结果3～6个月其GOS结果为,亚低温治疗组痊愈28例(45.2%),死亡10例(16.1%),常温组分别为18例(26.5%)和18例(26.5%),两组比较差异有显著意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组明显降低.且亚低温组能缩短脑水肿时间,降低脑水肿程度.亚低温能降低血糖.结论急性重型颅脑损伤早期采用亚低温治疗可降低死亡率,提高治愈率。