Cerebral rScO2 Measured by Near-Infrared Spectroscopy (NIRS) During Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review.

INTRODUCTION: Perinatal asphyxia, a leading cause of neonatal mortality and neurological sequelae, necessitates early detection of pathophysiological neurologic changes during hypoxic-ischaemic encephalopathy (HIE). This study aimed to review published data on rScO2 monitoring during hypothermia treatment in neonates with perinatal asphyxia to predict short- and long-term neurological injury. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Study identification was performed through a search between November and December 2021 in the electronic databases PubMed, Embase, Lilacs, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). The main outcome was short-term (Changes in brain magnetic resonating imaging) and long-term (In neurodevelopment) neurological injury. The study protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews) with CRD42023395438. RESULTS: 380 articles were collected from databases in the initial search. Finally, 15 articles were selected for extraction and analysis of the information. An increase in rScO2 measured by NIRS (Near-infrared spectroscopy) at different moments of treatment predicts neurological injury. However, there exists a wide variability in the methods and outcomes of the studies. CONCLUSION: High rScO2 values were found to predict negative outcomes, with substantial discord among studies. NIRS is proposed as a real-time bedside tool for predicting brain injury in neonates with moderate to severe HIE.

Asphyxia, Therapeutic Hypothermia, and Pulmonary Hypertension.

Neonates with a perinatal hypoxic insult and subsequent neonatal encephalopathy are at risk of acute pulmonary hypertension (aPH) in the transitional period. The phenotypic contributors to aPH following perinatal asphyxia include a combination of hypoxic vasoconstriction of the pulmonary vascular bed, right heart dysfunction, and left heart dysfunction. Therapeutic hypothermia is the standard of care for neonates with moderate-to-severe hypoxic ischemic encephalopathy. This review summarizes the underlying risk factors, causes of aPH in neonates with perinatal asphyxia, discusses the unique phenotypical contributors to disease, and explores the impact of the initial insult and subsequent therapeutic hypothermia on aPH.

Therapeutic hypothermia after perinatal asphyxia in Vietnam: medium-term outcomes at 18 months - a prospective cohort study.

AIM: To determine neurodevelopmental outcome at 18 months after therapeutic hypothermia for hypoxic-ischaemic encephalopathy (HIE) infants in Vietnam, a low-middle-income country. METHOD: Prospective cohort study investigating outcomes at 18 months in severely asphyxiated outborn infants who underwent therapeutic hypothermia for HIE in Hanoi, Vietnam, during the time period 2016-2019. Survivors were examined at discharge and at 6 and 18 months by a neonatologist, a neurologist and a rehabilitation physician, who were blinded to the infants' clinical severity during hospitalisation using two assessment tools: the Ages and Stages Questionnaire (ASQ) and the Hammersmith Infant Neurological Examination (HINE), to detect impairments and promote early interventions for those who require it. RESULTS: In total, 130 neonates, 85 (65%) with moderate and 45 (35%) with severe HIE, underwent therapeutic hypothermia treatment using phase change material. Forty-three infants (33%) died during hospitalisation and in infancy. Among the 87 survivors, 69 (79%) completed follow-up until 18 months. Nineteen children developed cerebral palsy (8 diplegia, 3 hemiplegia, 8 dyskinetic), and 11 had delayed neurodevelopment. At each time point, infants with a normal or delayed neurodevelopment had significantly higher ASQ and HINE scores (p<0.05) than those with cerebral palsy. CONCLUSION: The rates of mortality and adverse neurodevelopment rate were high and comparable to recently published data from other low-middle-income settings. The ASQ and HINE were useful tools for screening and evaluation of neurodevelopment and neurological function.

[Case Report about an Inpatient Suicide by Asphyxia without Strangulation]. / Fallbericht über einen Kliniksuizid durch Asphyxie ohne Strangulation.

A risk of suicide in the course of a psychiatric disorder will often be answered with an admission for inpatient psychiatric treatment, resulting in a high potential of suicidal behavior on the ward. Despite extensive safety precautions and therapeutic interventions, suicides still occur within psychiatric hospitals. Such incidents, known as inpatient suicides, are rare but significant, necessitating further examination. We present the case of a 91-year-old suicidal male patient, who committed suicide on an open ward on a Sunday morning by blocking his nostrils with cotton and tissue and breathing into a pillow, leading to death by asphyxia. The case report aims to draw attention to the possibility of this extraordinary method of suicide, demonstrating that a suicide can be accomplished in a psychiatric hospital even without the use of prohibited dangerous objects.

COMPARISON BETWEEN ACTIVE ABDOMINAL COMPRESSION-DECOMPRESSION CARDIOPULMONARY RESUSCITATION AND STANDARD CARDIOPULMONARY RESUSCITATION IN ASPHYCTIC CARDIAC ARREST RATS WITH MULTIPLE RIB FRACTURES.

ABSTRACT: Background: Active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR) is potentially more effective for cardiac arrest (CA) with multiple rib fractures. However, its effect on survival rates and neurological outcomes remains unknown. This study aimed to assess if AACD-CPR improves survival rates and neurological outcomes in a rat model of asphyctic CA with multiple rib fractures. Methods: Adult male Sprague-Dawley rats were randomized into three groups-AACD group (n = 15), standard cardiopulmonary resuscitation (STD-CPR) group (n = 15), and sham group (n = 10)-after bilateral rib fractures were surgically created and endotracheal intubation was performed. AACD-CPR and STD-CPR groups underwent 8 min of asphyxia followed by different CPR techniques. The sham group had venous catheterization only. Physiological variables and arterial blood gases were recorded at baseline and during a 4-h monitoring period. Neurological deficit scores (NDSs) and cumulative survival rates were assessed at 24, 48, and 72 h. NDS, serum biomarkers, and hippocampal neuron analysis were used to evaluate neurological outcomes. Results: No statistical differences were observed in the return of spontaneous circulation (ROSC), 24-, 48-, and 72-h survival rates between the AACD-CPR and STD-CPR groups. AACD-CPR rats had lower serum levels of neuron-specific enolase and S100B at 72 h post-ROSC, and higher NDS at 72 h post-ROSC compared with STD-CPR animals. Cellular morphology analysis, hematoxylin and eosin staining, and TUNEL/DAPI assays showed more viable neurons and fewer apoptotic neurons in the AACD-CPR group than in the STD-CPR group. Conclusions: AACD-CPR can achieve similar survival rates and better neurological outcome after asphyxial CA in rats with multiple rib fractures when compared with STD-CPR.

Comparison of hemodynamic effects of chest compression delivered via machine or human in asphyxiated piglets.

BACKGROUND: High-quality chest compressions (CC) are an important factor of neonatal resuscitation. Mechanical CC devices may provide superior CC delivery and improve resuscitation outcomes. We aimed to compare the hemodynamic effects of CC delivered by machine and human using a neonatal piglet model. METHODS: Twelve asphyxiated piglets were randomized to receive CC during resuscitation using an automated mechanical CC device ("machine") or the two-thumb encircling technique ("human"). CC was superimposed with sustained inflations. RESULTS: Twelve newborn piglets (age 0-3 days, weight 2.12 ± 0.17 kg) were included in the study. Machine-delivered CC resulted in an increase in stroke volume, and minimum and maximum rate of left ventricle pressure change (dp/dtmin and dp/dtmax) compared to human-delivered CC. CONCLUSIONS: During machine-delivered CC, stroke volume and left ventricular contractility were significantly improved. Mechanical CC devices may provide improved cardiopulmonary resuscitation outcomes in neonatal cardiac arrest induced by asphyxia. IMPACT: Machine chest compression leads to changes in hemodynamic parameters during resuscitation of asphyxiated neonatal piglets, namely greater stroke volume and left ventricular contractility, compared with standard two-thumb compression technique. Mechanical chest compression devices may provide improved cardiopulmonary resuscitation outcomes in neonatal and pediatric asphyxia-induced cardiac arrest.

Placental Histologic Abnormalities and 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: We aimed to examine the association between placental abnormalities and neurodevelopmental outcomes in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) that underwent therapeutic hypothermia. We hypothesized that subjects with acute placental abnormalities would have reduced risk of death or neurodevelopmental impairment (NDI) at 2 years of age after undergoing therapeutic hypothermia compared to subjects without acute placental changes. STUDY DESIGN: Among 500 subjects born at ≥36 weeks gestation with moderate or severe HIE enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, a placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute only, chronic only, or both acute and chronic histologic abnormalities. We calculated adjusted relative risks (aRRs) for associations between placental pathologic abnormalities and death or NDI at age 2 years, adjusting for HIE severity, treatment assignment, and site. RESULT: 321/500 subjects (64%) had available placental pathology reports. Placental abnormalities were characterized as acute only (20%), chronic only (21%), both acute and chronic (43%), and none (15%). The risk of death or NDI was not statistically different between subjects with and without an acute placental abnormality (46 vs. 53%, aRR 1.1, 95% confidence interval (CI): 0.9, 1.4). Subjects with two or more chronic lesions were more likely to have an adverse outcome than subjects with no chronic abnormalities, though this did not reach statistical significance (55 vs. 45%, aRR 1.24, 95% CI: 0.99, 1.56). CONCLUSION: Placental pathologic findings were not independently associated with risk of death or NDI in subjects with HIE. The relationship between multiple chronic placental lesions and HIE outcomes deserves further study.

Short-term neurological injury in newborns infants with overcooling in passive hypothermia and transferred to reference hospital in Colombia.

AIM: The aim of the study was to determine whether overcooling (temperature <33°C) during passive hypothermia when transporting neonates with perinatal asphyxia increased the risk of short-term neurological injury. METHODS: A retrospective observational study was performed. Newborns transferred to the LaCardio neonatal unit between January 2021 and April 2022 with moderate and severe perinatal asphyxia and who received passive hypothermia during transport were included. A temperature of <33°C was considered overcooling. A composite outcome of neurological injury was defined by the presence of abnormalities on brain magnetic resonance imaging, video telemetry, seizure before discharge or both. RESULTS: The study included 101 newborns. A total of 18 neonates had a temperature <33°C after transportation. Neurological injuries were present in 21.8% of the temperature <33°C group and 78.2% of the temperature ≥33°C group. Temperature <33°C at the end of transport (aOR 9.2, 95% CI 1.1-77.3) were associated with neurological injury before discharge from the unit. CONCLUSION: During transportation, overcooling in neonates with asphyxia increases the risk of neurological injury before discharge from the neonatal unit. It is important to qualify the transport team with adequate training and equipment for therapeutic hypothermia.

Multi-organ dysfunction in infants with acidosis at birth in the absence of moderate to severe hypoxic ischemic encephalopathy.

INTRODUCTION: Infants with perinatal asphyxia are at risk for organ failure aside from the brain, regardless of the severity of the asphyxial insult. We aimed to evaluate the presence of organ dysfunction other than the brain in newborns with moderate to severe acidosis at birth, in the absence of moderate to severe hypoxic ischemic encephalopathy. MATERIALS AND METHODS: Data of 2 years were retrospectively recorded. Late preterm and term infants admitted to the intensive care unit with ph < 7.10 and BE < -12 mmol/l in the first hour were included in the absence of moderate to severe hypoxic ischemic encephalopathy. Respiratory dysfunction, hepatic dysfunction, renal dysfunction, myocardial depression, gastrointestinal problems, hematologic system dysfunction, and circulatory failure were evaluated. RESULTS: Sixty-five infants were included [39 (37-40) weeks, 3040 (2655-3380) grams]. Fifty-six (86 %) infants had one or more dysfunction in any system [respiratory: 76.9 %, hepatic: 20.0 %, coagulation: 18.5 %, renal: 9.2 %, hematologic: 7.7 %, gastrointestinal: 3.0 %, and cardiac: 3.0 %]. Twenty infants had at least two affected systems. The incidence of coagulation dysfunctions was higher in the infants with severe acidosis (n = 25, ph < 7.00) than the infants with moderate acidosis (n = 40: pH = 7.00-7.10); 32 % vs 10 %; p = 0.03. CONCLUSIONS: Moderate to severe fetal acidosis is associated with the development of extra-cranial organ dysfunctions in infants who do not require therapeutic hypothermia. A monitoring protocol is needed for infants with mild asphyxia in order to identify and manage potential complications. Coagulation system should be carefully evaluated.

Characteristics of Children With Cerebral Palsy in the Post-Therapeutic Hypothermia Era.

Objectives: To explore the profile of children with cerebral palsy secondary to intrapartum asphyxia treated with therapeutic hypothermia after birth and to compare characteristics of children treated with therapeutic hypothermia with mild vs severe cerebral palsy outcome. Study Design: We identified all children treated with therapeutic hypothermia for intrapartum asphyxia in a single-center tertiary-level neonatal intensive care unit from 2008 to 2018 with a cerebral palsy outcome. We collected perinatal and outcome measures from patient charts. We searched the literature for characteristics of children with cerebral palsy prior to therapeutic hypothermia (historical cohort) to compare to our cohort. We subdivided our cohort into mild vs severe cerebral palsy and compared neonatal characteristics to identify predictors of severe phenotype. Results: Thirty of 355 cooled neonates (8%) developed cerebral palsy. More children had spastic quadriparesis and epilepsy, and fewer had visual impairment in the post-therapeutic hypothermia era compared to the historical cohort, but had similar Gross Motor Function Classification System scores. In our cohort, more children had severe (19 of 30, 63%) compared to mild cerebral palsy (11 of 30, 37%). The severe group had higher mean birth weight, lower 5- and 10-minute Apgar scores, and more often white matter injury with associated deep gray matter injury or near-total injury pattern (P < .05). Conclusions: Our data demonstrated more infants with severe rather than mild cerebral palsy in our cohort treated with therapeutic hypothermia. Birthweight, 5- and 10-minute Apgar scores, and magnetic resonance imaging (MRI) findings were significantly different between mild and severe phenotype groups. Our findings can guide clinicians how to better weigh these factors, when counseling parents in the neonatal period.

Front-line health professionals' recognition and responses to nonfatal strangulation events: An integrative review.

AIM: The aim of this study was to determine how front-line health professionals identify and manage nonfatal strangulation events. DESIGN: Integrative review with narrative synthesis was conducted. DATA SOURCES: A comprehensive database search was conducted in six electronic databases (CINAHL, Wed of Science, DISCOVER, SCOPUS, PubMed and Scholar) resulting in 49 potentially eligible full texts, reduced to 10 articles for inclusion after exclusion criteria were applied. REVIEW METHODS: An integrative review was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement guidelines. Data were extracted, and a narrative synthesis using Whittemore and Knafl (2005) framework was undertaken to determine how front-line health professionals identify and manage nonfatal strangulation events. RESULTS: The findings identified three main themes: an overall failure by health professionals to recognize nonfatal strangulation, a failure to report the event and a failure to follow up on victims after the event. Stigma and predetermined beliefs around nonfatal strangulation, along with a lack of knowledge about signs and symptoms, were the salient features in the literature. CONCLUSION: Lack of training and fear of not knowing what to do next are barriers to providing care to victims of strangulation. Failure to detect, manage and support victims will continue the cycle of harm through the long-term health effects of strangulation. Early detection and management of strangulation are essential to prevent health complications, particularly when the victims are exposed to such behaviours repeatedly. IMPACT: This review appears to be the first to explore how health professionals identify and manage nonfatal strangulation. It identified the significant need for education and robust and consistent screening and discharge policies to assist health providers of services where victims of nonfatal strangulation attend. NO PATIENT OR PUBLIC CONTRIBUTION: This review contains no patient or public contribution since it was examining health professionals' knowledge of identifying nonfatal strangulation and the screening and assessment tools used in clinical practice.

Increase in Standardized Management of Neonates with Hypoxic-Ischemic Encephalopathy Since Implementation of a Patient Register.

The Swiss National Asphyxia and Cooling Register was implemented in 2011. This study assessed quality indicators of the cooling process and (short-term) outcomes of neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) longitudinally over time in Switzerland. This is a multicenter national retrospective cohort study of prospectively collected register data. Quality indicators were defined for longitudinal comparison (2011-2014 vs. 2015-2018) of processes of TH and (short-term) outcomes of neonates with moderate-to-severe HIE. Five hundred seventy neonates receiving TH in 10 Swiss cooling centers were included (2011-2018). Four hundred forty-nine (449/570; 78.8%) neonates with moderate-to-severe HIE received TH according to the Swiss National Asphyxia and Cooling Register Protocol. Quality indicators of processes of TH improved in 2015-2018 (compared with 2011-2014): less passive cooling (p = 0.013), shorter time to reach target temperature (p = 0.002), and less over- or undercooling (p < 0.001). In 2015-2018, adherence to performing a cranial magnetic resonance imaging after rewarming improved (p < 0.001), whereas less cranial ultrasounds were performed on admission (p = 0.012). With regard to quality indicators of short-term outcomes, persistent pulmonary hypertension of the neonate was reduced (p = 0.003), and there was a trend toward less coagulopathy (p = 0.063) in 2015-2018. There was no statistically significant change in the remaining processes and outcomes. The Swiss National Asphyxia and Cooling Register is well implemented with good overall adherence to the treatment protocol. Management of TH improved longitudinally. Continuous reevaluation of register data is desirable for quality assessment, benchmarking, and maintaining international evidence-based quality standards.

On-site treatment of avalanche victims: Scoping review and 2023 recommendations of the international commission for mountain emergency medicine (ICAR MedCom).

INTRODUCTION: The International Commission for Mountain Emergency Medicine (ICAR MedCom) developed updated recommendations for the management of avalanche victims. METHODS: ICAR MedCom created Population Intervention Comparator Outcome (PICO) questions and conducted a scoping review of the literature. We evaluated and graded the evidence using the American College of Chest Physicians system. RESULTS: We included 120 studies including original data in the qualitative synthesis. There were 45 retrospective studies (38%), 44 case reports or case series (37%), and 18 prospective studies on volunteers (15%). The main cause of death from avalanche burial was asphyxia (range of all studies 65-100%). Trauma was the second most common cause of death (5-29%). Hypothermia accounted for few deaths (0-4%). CONCLUSIONS AND RECOMMENDATIONS: For a victim with a burial time ≤ 60 minutes without signs of life, presume asphyxia and provide rescue breaths as soon as possible, regardless of airway patency. For a victim with a burial time > 60 minutes, no signs of life but a patent airway or airway with unknown patency, presume that a primary hypothermic CA has occurred and initiate cardiopulmonary resuscitation (CPR) unless temperature can be measured to rule out hypothermic cardiac arrest. For a victim buried > 60 minutes without signs of life and with an obstructed airway, if core temperature cannot be measured, rescuers can presume asphyxia-induced CA, and should not initiate CPR. If core temperature can be measured, for a victim without signs of life, with a patent airway, and with a core temperature < 30 °C attempt resuscitation, regardless of burial duration.

Identifying Genetic Susceptibility in Neonates With Hypoxic-Ischemic Encephalopathy: A Retrospective Case Series.

Neonatal hypoxic-ischemic encephalopathy is a clinical phenomenon that often results from perinatal asphyxia. To mitigate secondary neurologic injury, prompt initial assessment and diagnosis is needed to identify patients eligible for therapeutic hypothermia. However, occasionally neonates present with a clinical picture of hypoxic-ischemic encephalopathy without significant risk factors for perinatal asphyxia. We hypothesized that in patients with genetic abnormalities, the clinical manifestation of those abnormalities may overlap with hypoxic-ischemic encephalopathy criteria, potentially contributing to a causal misattribution. We reviewed 210 charts of infants meeting local protocol criteria for moderate to severe hypoxic-ischemic encephalopathy in neonatal intensive care units in Calgary, Alberta. All patients that met criteria for therapeutic hypothermia were eligible for the study. Data were collected surrounding pregnancy and birth histories, as well as any available genetic or metabolic testing including microarray, gene panels, whole-exome sequencing, and newborn metabolic screens. Twenty-eight patients had genetic testing such as microarray, whole-exome sequencing, or a gene panel, because of clinical suspicion. Ten of 28 patients had genetic mutations, including CDKL5, pyruvate dehydrogenase, CFTR, CYP21A2, ISY1, KIF1A, KCNQ2, SCN9A, MTFMT, and NPHP1. All patients lacked significant risk factors to support a moderate to severe hypoxic-ischemic encephalopathy diagnosis. Treatment was changed in 2 patients because of confirmed genetic etiology. This study demonstrates the importance of identifying genetic comorbidities as potential contributors to a hypoxic-ischemic encephalopathy phenotype in neonates. Early identification of clinical factors that support an alternate diagnosis should be considered when the patient's clinical picture is not typical of hypoxic-ischemic encephalopathy and could aid in both treatment decisions and outcome prognostication.

Kidney outcomes in early adolescence following perinatal asphyxia and hypothermia-treated hypoxic-ischaemic encephalopathy.

BACKGROUND: Acute kidney injury (AKI) remains common among infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). Little is known about long-term kidney outcomes following hypothermia treatment. We recently reported that 21% of survivors of hypothermia-treated HIE had decreased estimated glomerular filtration rate (eGFR) based on plasma creatinine in early adolescence. Here, we assessed kidney functions more comprehensively in our population-based cohort of children born in Stockholm 2007-2009 with a history of hypothermia-treated HIE. METHODS: At 10-12 years of age, we measured cystatin C (cyst C) to estimate GFR. Children with decreased cyst C eGFR also underwent iohexol clearance examination. We measured urine-albumin/creatinine ratio, blood pressure (BP) and kidney volume on magnetic resonance imaging. Fibroblast growth factor 23 (FGF 23) levels in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). Outcomes were compared between children with and without a history of neonatal AKI. RESULTS: Forty-seven children participated in the assessment. Two children (2/42) had decreased cyst C eGFR, for one of whom iohexol clearance confirmed mildly decreased GFR. One child (1/43) had Kidney Disease Improving Global Outcomes (KDIGO) category A2 albuminuria, and three (3/45) had elevated office BP. Subsequent ambulatory 24-h BP measurement confirmed high normal BP in one case only. No child had hypertension. Kidney volume and FGF 23 levels were normal in all children. There was no difference in any of the parameters between children with and without a history of neonatal AKI. CONCLUSION: Renal sequelae were rare in early adolescence following hypothermia-treated HIE regardless of presence or absence of neonatal AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Pursuit of Medical Care for Female Victims of Nonfatal Strangulation at the Time of Police Response.

Survivors of nonfatal strangulation face a number of physical health consequences, some of which can be fatal if untreated. Despite the known health risks and connections to delayed fatalities, little is known about strangulation and victims' pursuit of medical care. Using data collected from prosecutors' case files (n = 143), this study attempts to understand what factors contribute to victims receiving medical attention following a nonfatal strangulation assault reported to police. Findings indicate that the suspect disrupting an emergency call increases the likelihood of the victim pursuing medical care. Implications are discussed.

Assessing Neurovascular Coupling Using Wavelet Coherence in Neonates with Asphyxia.

Brain monitoring is important in neonates with asphyxia in order to assess the severity of hypoxic ischaemic encephalopathy (HIE) and identify neonates at risk of adverse neurodevelopmental outcome. Previous studies suggest that neurovascular coupling (NVC), quantified as the interaction between electroencephalography (EEG) and near-infrared spectroscopy (NIRS)-derived regional cerebral oxygen saturation (rSO2) is a promising biomarker for HIE severity and outcome. In this study, we explore how wavelet coherence can be used to assess NVC. Wavelet coherence was computed in 18 neonates undergoing therapeutic hypothermia in the first 3 days of life, with varying HIE severities (mild, moderate, severe). We compared two pre-processing methods of the EEG prior to wavelet computation: amplitude integrated EEG (aEEG) and EEG bandpower. Furthermore, we proposed average real coherence as a biomarker for NVC. Our results indicate that NVC as assessed by wavelet coherence between EEG bandpower and rSO2 can be a valuable biomarker for HIE severity in neonates with peripartal asphyxia. More specifically, average real coherence in a very low frequency range (0.21-0.83 mHz) tends to be high (positive) in neonates with mild HIE, low (positive) in neonates with moderate HIE, and negative in neonates with severe HIE. Further investigation in a larger patient cohort is needed to validate our findings.

[Effect of electroacupuncture at Baihui ameliorated neurologic deficit and hemodynamic stability in rat model of post-cardiac arrest syndrome].

OBJECTIVE: To observe the results of electroacupuncture (EA) on the resuscitation of a rat model of asphyxia cardiac arrest (CA). And to explore its effect on the neurologic deficits and hemodynamic instability of post-cardiac arrest syndrome (PCAS). METHODS: A total of 107 male SD rats were randomly divided into sham, CA, and EA groups. Each group received arterial catheterization and tracheal intubation. The sham group was not induced asphyxia. Asphyxial cardiac arrest was established by endotracheal tube clamping. Rats in the CA group received basic respiratory support and fluid resuscitation in return of spontaneous circulation (ROSC) and rats in the EA group received EA at Baihui based on the treatment of CA group after ROSC, with a dense-dispersed wave at frequencies of 4-20 Hz, while the current intensity was adjusted minimum to induce a twitch of the scalp, the course of treatment was 30 minutes. The baseline data, hemodynamics after ROSC, neurological deficit score (NDS), pathological changes of brain tissue, and levels of serum biomarker were recorded and compared among the three groups. The 72-hour survival of rats was analyzed by Kaplan-Meier survival curve. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of necrotic neurons in the hippocampal CA1 region of rat brain. Meanwhile, Nissl staining and TdT-mediated dUTP nick-end labeling (TUNEL) were used to detect cell apoptosis and injury. RESULTS: Compared with the CA group, the mean arterial pressure (MAP) in the EA group increased significantly at 15 minutes after ROSC [mmHg (1 mmHg ≈ 0.133 kPa): 125.00 (94.00, 136.25) vs. 92.00 (72.00, 122.50), P < 0.05]. There was no significant difference in the NDS score between the EA group and the sham group. Still, the NDS score of the rats in the CA group at 6 hours after ROSC were significantly lower than that in the sham group (46.00±10.61 vs. 80.00±0.00, P < 0.05). Kaplan-Meier survival curve analysis showed that EA did not improve the 72-hour survival rate of rats (100% in the sham group, 25% in the CA group, and 30% in the EA group, P > 0.05). The analysis by TUNEL showed that the apoptosis rate of neurons in CA1 region of the hippocampus in EA group at 6 hours after ROSC was significantly lower than that in CA group [(62.84±2.67)% vs. (71.29±3.70)%, P < 0.05]. Compared with the CA group, the level of serum S100 calcium binding protein B (S100B) in the EA group at 6 hours after ROSC was significantly lower (ng/L: 19.30±13.87 vs. 132.28±31.67, P < 0.05), but there were no significant differences in the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) between these two groups. CONCLUSIONS: In the present study, EA at Baihui can stabilize the hemodynamic, moreover, it has a particular neuroprotective effect on PCAS rats. Still, EA at Baihui does not reduce the systemic inflammatory response and improve the survival rate of rats, and its mechanism remains to be verified in further research.

Urinary metabotypes of newborns with perinatal asphyxia undergoing therapeutic hypothermia.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the "HIE" group), and 32 did not (the "no HIE" group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the "HIE" and "no HIE" groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA.

Therapeutic Hypothermia for Perinatal Asphyxia in India-Experience and Evidence.

Therapeutic hypothermia is an established therapy with proven benefit for term neonates with moderate and severe hypoxic-ischemic encephalopathy (HIE). Many centers in India have started therapeutic cooling of asphyxiated infants. There is enough evidence for the beneficial effect of cooling from the randomized trials conducted in India. However, the recently published hypothermia for encephalopathy in low- and middle-income countries (HELIX) trial has contrasting findings. In this context, this review is written summarizing the available experience and evidence for therapeutic hypothermia for perinatal asphyxia in India.