Nutrition of Newborns with Hypoxic-Ischaemic Encephalopathy during Therapeutic Hypothermia - A Survey of Practice in Polish Neonatal Care Units.

BACKGROUND: The nutritional practice for newborns with hypoxic-ischaemic encephalopathy during therapeutic hypothermia differs among Polish neonatal care units, as no guidelines are provided. We assessed the prevailing procedures. MATERIAL AND METHODS: Data was collected through an anonymous, web-based questionnaire. We surveyed aspects of the current nutritional practices and the reasoning behind the choice of the feeding strategy. RESULTS: Thirty-one responses were obtained (31/33, 94%). Based on participants' estimations, 342 newborns are diagnosed with hypoxic-ischaemic encephalopathy and qualified for therapeutic hypothermia annually. Among them, almost ⅓ is fed exclusively parenterally, while 71% both ways-parenterally and enterally. In the vast majority of units, the introduction of enteral nutrition takes place during the first 48 hours of therapeutic hypothermia, and breast milk is primarily provided, although with substantial first feeding volume differentiation (an average of 2,9 ml/kg (0,3 - 10ml/kg)). Adverse events, such as necrotising enterocolitis, sepsis, and glycemia level disturbances that derive from the initiation of enteral nutrition, are difficult to estimate as no official statistics are provided. CONCLUSIONS: The majority of newborns after hypoxic-ischaemic encephalopathy treated with therapeutic hypothermia are fed both parenterally and enterally during the procedure, predominantly with expressed or donor breast milk. However, due to the lack of nutritional guidelines, significant variability of nutritional strategies concerning initiation time, type and volume of enteral feeds given is noted. Therefore, further studies are required to clarify feeding recommendations.

Non-pharmacological interventions for traumatic brain injury.

Heterogeneity and variability of symptoms due to the type, site, age, sex, and severity of injury make each case of traumatic brain injury (TBI) unique. Considering this, a universal treatment strategy may not be fruitful in managing outcomes after TBI. Most of the pharmacological therapies for TBI aim at modifying a particular pathway or molecular process in the sequelae of secondary injury rather than a holistic approach. On the other hand, non-pharmacological interventions such as hypothermia, hyperbaric oxygen, preconditioning with dietary adaptations, exercise, environmental enrichment, deep brain stimulation, decompressive craniectomy, probiotic use, gene therapy, music therapy, and stem cell therapy can promote healing by modulating multiple neuroprotective mechanisms. In this review, we discussed the major non-pharmacological interventions that are being tested in animal models of TBI as well as in clinical trials. We evaluated the functional outcomes of various interventions with an emphasis on the links between molecular mechanisms and outcomes after TBI.

Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis. METHODS: The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects. RESULTS: Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14-38.83; however, the overall evidence quality was low for the small sample size. CONCLUSIONS: Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.

Effect of adjuvant thiamine and ascorbic acid administration on the neurologic outcomes of out-of-hospital cardiac arrest patients: A before-and-after study.

AIM: This study aimed to evaluate the impact of early thiamine and ascorbic acid administration on the neurologic outcome in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). METHODS: This before-and-after cohort study used data extracted from two hospitals of the Korean Hypothermia Network prospective registry. The treatment group incorporated patients enrolled from December 2019 to May 2021, that received intravenous thiamine (200 mg) and ascorbic acid (3 g) at 12-hour intervals for a total of six doses. The control group incorporated those enrolled from May 2018 to November 2019. The one-month good neurologic outcome, defined as a Cerebral Performance Category score ≤ 2, between the groups was evaluated using inverse probability of treatment weighting (IPTW). RESULTS: Among the 234 OHCA survivors with TTM, 102 were included in the treatment group and 132 were included in the control group. The one-month (31.4 % vs. 29.5 %, respectively; P = 0.76) good neurologic outcome rates did not differ between the treatment and control groups. After adjusting using the IPTW, vitamin supplementation was not associated with good neurologic outcome (odds ratio [OR], 1.134; 95 % confidence interval [CI], 0.644-1.999; P = 0.66). In subgroup analysis, vitamin administration was significantly associated with a good neurologic outcome in older (≥65 years) patients (adjusted OR, 5.53; 95 % CI, 1.21-25.23; P = 0.03). CONCLUSION: Adjuvant thiamine and ascorbic acid administration in OHCA survivors with TTM did not improve their neurologic outcome after one month. Further clinical trials are warranted.

Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.

BACKGROUND AND AIMS: Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. METHODS: This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. RESULTS: Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790-0.828), 0.835 (95% CI 0.816-0.852) for the TTM-score, 0.820 (95% CI 0.800-0.839) for the CAHP-score and 0.770 (95% CI 0.748-0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. CONCLUSIONS: The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials.

Improving Quality of Life During Chemotherapy: Cannabinoids, Cryotherapy, and Scalp Cooling.

There have been significant advances in the treatment of cancer in the past decade. However, patients continue to suffer from significant side effects of antineoplastic agents that greatly affect their quality of life (QOL), including chemotherapy-induced nausea and vomiting (CINV), chemotherapy-induced peripheral neuropathy (CIPN), and chemotherapy-induced alopecia (CIA). This review aims to provide an updated overview of emerging strategies for the management and prevention of these immediate and long-lasting side effects. The use of integrative medicine including cannabis continues to evolve in the realm of CINV and cancer-related anorexia. Although no pharmaceutical agent has been approved for the prevention of CIPN, cryotherapy, compression therapy and, more recently, cryocompression therapy have shown benefit in small trials, but there are concerns with tolerability especially related to cryotherapy. More data are necessary to determine an effective and tolerable option to prevent CIPN in large, randomized studies. Scalp cooling (SC), which has a similar mechanism to cryotherapy and compression therapy for CIPN prevention, has proven to be an effective and tolerable approach in randomized studies and has significantly limited CIA, an entity that definitively affects the QOL of patients living with cancer. Taken together, cannabis, cryotherapy, compression and cryocompression therapy, and SC all strive to improve the QOL of patients living with cancer by minimizing the side effects of chemotherapeutic agents.

[A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent]. / 基于亚低温床垫与高压氧舱结合的新生儿智能调控系统.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.

Feasibility of Minimal Enteral Nutrition During Therapeutic Hypothermia for Perinatal Asphyxia: A Five-Year Multicenter Experience from South India.

Limited evidence shows minimal enteral nutrition (MEN) during therapeutic hypothermia (TH) in neonates to be feasible and have benefits of shorter time to full-feeds. This study aimed to assess the feasibility of MEN during TH. MEN was initiated after 12 h if there were no altered aspirates, abdominal distension, and inotrope requirement. The authors retrospectively analyzed the records from May 2017 to April 2022. The number of episodes of feed intolerance and the length of hospital stay were the key outcomes. A total of 99 neonates were fed during cooling. MEN could be initiated at a median duration (IQR) of 24 (24-30) h. There were 9 (9%) neonates with feed intolerance during TH. None had necrotizing enterocolitis. Ninety-two (93%) neonates were discharged, with a median hospital stay (IQR) of 9 d (6-15). Hence, MEN during TH is feasible and provides a rationale for future controlled trials.

Effects of temperature control on hyperthermia-related cardiac dysfunction in a porcine model of cardiac arrest.

The outcome of cardiac arrest is worse when there is fever after spontaneous circulation is restored (ROSC). The purpose of this study was to investigate the mechanism of post-ROSC cardiac dysfunction after hyperthermia treatment and the effects of temperature control. Twenty-four male Bama minipigs were randomized into 3 groups (8 per group): CPR + controlled normothermia (CN), CPR + hyperthermia (HT), and CPR + therapeutic mild hypothermia (TMH). Defibrillation was given to pigs with ventricular fibrillation after 8 min of untreated fibrillation. Subsequently, these animals received the post-ROSC treatments of hyperthermia (38 °C), controlled normothermia (37 °C) or hypothermia (33 °C) according to the groups. Hemodynamic parameters, left ventricular ejection fraction, blood samples and myocardial tissues were assessed. At 24 h after the post-ROSC treatments, the pigs treated with hyperthermia showed increments in heart rate and plasma cardiac troponin I, and decreases in mean arterial pressure, cardiac index, and left ventricular ejection fraction, compared to those with the controlled normothermia pigs. However, the deterioration of the above parameters can be attenuated by TMH. The pigs in the TMH group also had a reduced percentage of apoptotic cardiomyocytes, an increased anti-apoptotic Bcl-2/Bax ratio and a decreased caspase-3 activity in myocardium, as compared with both controlled normothermia and hyperthermia pigs. In conclusion, hyperthermia is associated with a worse myocardial dysfunction. TMH improves hyperthermia-induced myocardial dysfunction by attenuating apoptosis in a porcine model of cardiac arrest.

A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent / 中国当代儿科杂志

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.

A novel scoring system (YASHMA) predicting brain injury in asphyxiated newborns.

BACKGROUND: Hypoxic-ischemic encephalopathy is a complication of adverse intrapartum events and birth asphyxia resulting in brain injury and mortality in late preterm and term newborns. OBJECTIVES: In this study, we aimed to predict brain damage on magnetic resonance imaging (MRI) with a new scoring system. METHODS: Yieldly And Scorable Holistic Measuring of Asphyxia (YASHMA) is generated for detection of brain injury in asphyxiated newborns. Total scores were calculated according to scores of birth weight, gestation weeks, APGAR scores at first and fifth minutes, aEEG patterns and epileptic status of patients. The major outcome of the scoring system was to determine correlation between poor scores and neonatal brain injury detected on MRI. RESULTS: In hypothermia group with brain injury, low gestational weeks and lowest APGAR scores, abnormal aEEG findings were statistically different from others. YASHMA scores were statistically significant with high sensitivity, specificity, AUC and 95% confidence interval values. CONCLUSIONS: YASHMA scoring system is feasible and can be suggestive for detecting brain injury in low-income countries.

A chronotherapeutics-applicable multi-target therapeutics based on AI: Example of therapeutic hypothermia.

Nowadays, the complexity of disease mechanisms and the inadequacy of single-target therapies in restoring the biological system have inevitably instigated the strategy of multi-target therapeutics with the analysis of each target individually. However, it is not suitable for dealing with the conflicts between targets or between drugs. With the release of high-precision protein structure prediction artificial intelligence, large-scale high-precision protein structure prediction and docking have become possible. In this article, we propose a multi-target drug discovery method by the example of therapeutic hypothermia (TH). First, we performed protein structure prediction for all protein targets of each group by AlphaFold2 and RoseTTAFold. Then, QuickVina 2 is used for molecular docking between the proteins and drugs. After docking, we use PageRank to rank single drugs and drug combinations of each group. The ePharmaLib was used for predicting the side effect targets. Given the differences in the weights of different targets, the method can effectively avoid inhibiting beneficial proteins while inhibiting harmful proteins. So it could minimize the conflicts between different doses and be friendly to chronotherapeutics. Besides, this method also has potential in precision medicine for its high compatibility with bioinformatics and promotes the development of pharmacogenomics and bioinfo-pharmacology.

Early versus delayed enteral nutrition for neonatal hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: a randomized controlled trial.

BACKGROUND: The practice of therapeutic hypothermia (TH) is widely used for neonatal hypoxic-ischemic encephalopathy (HIE) despite its corresponding feeding strategies are still controversial. This randomized controlled trial (RCT) demonstrated to evaluate the effect of early vs. delayed enteral nutrition on the incidence of feeding intolerance (FI) and other association during TH. METHODS: This single center, parallel-group, and no-blinded RCT was processed in a level III, and academic neonatal intensive care unit. Infants who were diagnosed with HIE and undertaken TH from September 2020 to August 2021 were enrolled. Participants were randomized to receive enteral nutrition either during TH/rewarming (early enteral nutrition, EEN) or after TH (delayed enteral nutrition, DEN) according to a recommend enteral feeding protocol. All data were analyzed using SPSS 26.0 software with a p-value< 0.05 was considered statistically significant. RESULTS: Ninety-two infants were enrolled after randomization, but 12 (13.04%) cases including 3 (3.26%) deaths were excluded from eventually analyzed, who did not initiate or discontinue the intervention. 80 cases (42 and 38 in the EEN and DEN group, respectively) who completed the interventions were eventually analyzed. Besides initial time of enteral feeds, two groups had processed the same feeding method. Total 23 (25.0%) cases developed FI, and no difference of morbidity was found between two groups (23.4% vs 26.7%, p = 0.595; Log Rank, p = 0.803). There was no case died or developed late-onset bloodstream and no difference of the incidence of hypoglycemia or weight gain was found (p > 0.05). The percentage of infants who had not reaching the goal of full enteral feeding volume between the two groups was similar (21.43% vs 23.68%, p = 0.809). The average time of parenteral nutrition, reaching full enteral feeds and hospital stay were shorter in the EEN group compared with the DEN group with significant differences (8.81 ± 1.67 vs 10.61 ± 2.06 days, p < 0.001; 9.91 ± 1.88 vs 12.24 ± 2.50 days, p < 0.001; 12.55 ± 4.57 vs 16.47 ± 5.27 days, p = 0.001 respectively). CONCLUSIONS: Compared with delayed enteral nutrition, introduction of early enteral nutrition according to a recommend feeding strategy for neonatal HIE undergoing TH may be feasible and safe.FI is frequent in this high-risk group of infants which should not be ignored during feeding process. TRIAL REGISTRATION: The Chinese Clinical Trial Registry,ChiCTR2000038193, 2020-9-13, https://www.chictr.org.cn .

Reassessment of mitochondrial cyclophilin D as a target for improving cardiac arrest outcomes in the era of therapeutic hypothermia.

Uncertainty exists regarding whether cyclophilin D (CypD), a mitochondrial matrix protein that plays a key role in ischemia-reperfusion injury, can be a pharmacological target for improving outcomes after cardiac arrest (CA), especially when therapeutic hypothermia is used. Using CypD knockout mice (CypD-/-), we investigated the effects of loss of CypD on short-term and medium-term outcomes after CA. CypD-/- mice or their wild-type (WT) littermates underwent either 5 minute CA followed by resuscitation with and/or without hypothermia at 33°C-34°C (targeted temperature reached within minutes after resuscitation), or a sham procedure. Brain and cardiac injury were assessed using echocardiography, neurological scores, MRI and biomarkers. Seven day survival was compared using Kaplan-Meier estimates. The rate of restoration of spontaneous circulation was significantly higher in CypD-/- mice (with shorter cardiac massage duration) than in WT mice (P < 0.05). Loss of CypD significantly attenuated CA-induced release of troponin and S100ß protein, and limited myocardial dysfunction at 150 minutes after CA. Loss of CypD combined with hypothermia led to the best neurological and MRI scores at 24 hours and highest survival rates at 7 days compared to other groups (P < 0.05). In animals successfully resuscitated, loss of CypD had no benefits on day 7 survival while hypothermia was highly protective. Pharmacological inhibition of CypD with cyclosporine A combined with hypothermia provided similar day 7 survival than loss of CypD combined with hypothermia. CypD is a viable target to improve success of cardiopulmonary resuscitation but its inhibition is unlikely to improve long-term outcomes, unless therapeutic hypothermia is associated.

Bovine Lactoferrin Alleviates Pulmonary Lipid Peroxidation and Inflammatory Damage in Heat Stroke Rats.

Lung injury occurring in the early stage of heat stroke (HS) leads to hypoxia and further aggravation of other organic damage. Lactoferrin (LF) is an iron binding protein with anti-inflammatory and antioxidant effects. This study focuses on the protection of preadministration of bovine lactoferrin (BLF) against lung injury in rats with HS. Sixty-four Sprague-Dawley male rats were divided into four groups randomly: control (CON)+phosphate-buffered saline (PBS) (n = 16), HS+PBS (n = 16), HS+low-dose BLF (LBLF) (n = 16), and HS+high-dose BLF (HBLF) (n = 16). CON+PBS and HS+PBS were preadministered 10 mL/kg PBS for 1 week. HS+LBLF and HS+HBLF were preadministered 100 and 200 mg/kg BLF for 1 week, respectively. The HS onset time and the survival rate were recorded, and bronchoalveolar lavage fluid was obtained to measure protein concentration. Lung was obtained for pathological analysis and wet/dry weight ratio measurement; later, the content of malondialdehyde (MDA), activity of myeloperoxidase (MPO), and superoxide dismutase (SOD) were measured in lung tissue homogenate. The results indicated that BLF preadministration could delay the HS onset time, enhance the survival rate, the levels of serum inflammatory cytokine and MDA content in HS+LBLF and HS+HBLF showed significant reduction compared with HS+PBS, while a significant elevation of SOD activity and reduction of MPO activity in HS+HBLF. Our results demonstrate that BLF preadministration could relieve lung injury in HS rats by enhancing thermal endurance, and alleviating serum inflammatory response and pulmonary oxidative stress damage.

The Association of Serum Magnesium Levels and QT Interval with Neurological Outcomes After Targeted Temperature Management.

Targeted temperature management (TTM) is associated with corrected QT (QTc) prolongation and decrease in serum magnesium (Mg) levels that may lead to recurrent ventricular arrhythmia and poor neurological outcomes. We aimed to evaluate the association between QTc interval and Mg levels during TTM with neurological outcomes. We reviewed the electrocardiograms of 366 patients who underwent TTM during the induction, maintenance, and rewarming phase after cardiac arrest. We reviewed the association of change in QTc interval, and Mg levels with neurological outcomes. In total, 71.3% of the patients had a significant increase in QTc interval defined as >60 ms or any QTc >500 ms during TTM. Poor neurological outcome was associated with persistent prolongation of QTc after rewarming (507 vs. 483 ms, p = 0.046) and higher Mg levels at presentation (2.08 ± 0.41 mg/dL, p = 0.014). Supplemental Mg did not have any significant change in their QTc. Patients with prolonged QTc during TTM should be promptly evaluated for QTc-prolonging factors given its association with worse neurological outcomes. The inverse correlation between Mg levels and poor neurological outcomes deserves further investigation.

Noninvasive monitoring of evolving urinary metabolic patterns in neonatal encephalopathy.

BACKGROUND: Infants with moderate and severe neonatal encephalopathy (NE) frequently suffer from long-term adverse outcomes. We hypothesize that the urinary metabolome of newborns with NE reflects the evolution of injury patterns observed with magnetic resonance imaging (MRI). METHODS: Eligible patients were newborn infants with perinatal asphyxia evolving to NE and qualifying for therapeutic hypothermia (TH) included in the HYPOTOP trial. MRI was employed for characterizing brain injury. Urine samples of 55 infants were collected before, during, and after TH. Metabolic profiles of samples were recorded employing three complementary mass spectrometry-based assays, and the alteration of detected metabolic features between groups was assessed. RESULTS: The longitudinal assessment revealed significant perturbations of the urinary metabolome. After 24 h of TH, a stable disease pattern evolved characterized by the alterations of 4-8% of metabolic features related to lipid metabolism, metabolism of cofactors and vitamins, glycan biosynthesis and metabolism, amino acid metabolism, and nucleotide metabolism. Characteristic metabolomic fingerprints were observed for different MRI injury patterns. CONCLUSIONS: This study shows the potential of urinary metabolic profiles for the noninvasive monitoring of brain injury of infants with NE during TH. IMPACT: A comprehensive approach for the study of the urinary metabolome was employed involving a semi-targeted capillary electrophoresis-time-of-flight mass spectrometry (TOFMS) assay, an untargeted ultra-performance liquid chromatography (UPLC)-quadrupole TOFMS assay, and a targeted UPLC-tandem MS-based method for the quantification of amino acids. The longitudinal study of the urinary metabolome identified dynamic metabolic changes between birth and until 96 h after the initiation of TH. The identification of altered metabolic pathways in newborns with pathologic MRI outcomes might offer the possibility of developing noninvasive monitoring approaches for personalized adjustment of the treatment and for supporting early outcome prediction.

Hypothermia therapy for the treatment of acute myocardial infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: In patients with acute myocardial infarction (AMI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We performed a protocol for systematic review and meta-analysis to investigate the effect of systemic therapeutic hypothermia in patients with AMI receiving PCI. METHODS: This study will use the Cochrane Library, Web of Science, PubMed, Embase, Allied and Complementary Medicine Database, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and Ongoing Clinical Trials Database. The search terms were hypothermia, cooling, myocardial infarction, myocardial ischemia and acute coronary syndrome. Quality assessment of the included studies was evaluated using the Cochrane risk of bias assessment tool. Statistical analyses were performed using RevMan 5.4 software. RESULTS: The findings of this study will be submitted to peer-reviewed journals for publication. CONCLUSION: This systematic review will provide evidence to determine whether hypothermia therapy is an effective and safe intervention for patients with AMI receiving PCI.Registration number: 10.17605/OSF.IO/9XJSB.