Initiation Of Therapeutic Hypothermia Research Articles

Therapeutic hypothermia: A descriptive, cohort study conducted over 10 years at a tertiary care public hospital.

Introduction. Therapeutic hypothermia (TH) reduces the risk of death or disability in children with moderate to severe hypoxic ischemic encephalopathy (HIE). Objective. To describe a population of patients with HIE that required TH and their course until discharge. Population and methods. Retrospective, descriptive, cohort study. All patients admitted to TH between 2013 and 2022 were studied. Epidemiological, clinical, monitoring, and treatment data were assessed, together with supplementary tests and condition at discharge. Risk factors were compared between deceased patients and survivors; and, among the latter, those requiring special healthcare needs (SHCN) at discharge. Results. A total of 247 patients were included. Mortality: 11%. Most common sentinel event: prolonged second stage of labor (39%). Treatment initiation: median of 5 hours of life. Seizures: 57%. Intravenous erythropoietin: 66.7%. Abnormal pattern in brain function monitoring: 52%. Normalization of monitoring: median of 24 hours. Pathological magnetic resonance imaging: 42%. Predictor variables of mortality: severe Sarnat and Sarnat staging and pathological ultrasound upon admission. Conclusion. The overall mortality rate was 11%. Referrals increased more markedly since 2018. The time of TH initiation was later than in previous reports. Severe neurological signs as per the Sarnat and Sarnat staging and a pathological baseline cranial ultrasound were independent predictors of mortality at discharge. Patients with SHCN at discharge showed a normalized tracing in the amplitude-integrated electroencephalography performed later. The most common finding in the magnetic resonance imaging was basal ganglia involvement. No statistically significant differences were observed in terms of clinical characteristics or complications among patients who received erythropoietin.

Amplitude-Integrated EEG in Infants at Risk of Hypoxic-Ischemic Encephalopathy: A Feasibility Study in Road and Air Transport in Western Australia.

Infants at risk of HIE require early identification and initiation of therapeutic hypothermia (TH). Earlier treatment with TH is associated with better outcomes. aEEG is frequently used when making the decision whether to commence TH. As this is often limited to tertiary centers, TH may be delayed if the infant requires transport to a center that provides it. We aimed to provide a method for the application of amplitude-integrated electroencephalogram (aEEG) and to determine the feasibility of acquiring clinically meaningful information during transport. All infants ≥35 weeks, at risk of HIE at referral, were eligible for inclusion. Scalp electrodes were placed in the C3-C4; P3-P4 position on the infant's scalp and connected to the aEEG amplifier. The aEEG amplifier was, in turn, connected to a clinical tablet computer with EEG software to collect and analyze aEEG information. Recordings were reviewed by the chief principal investigator and two independent reviewers (blinded) for background trace and artifact. Predefined criteria for data quality were set to movement artifacts and software impedance notifications. Surveys were completed by healthcare staff and parents for acceptability and ease of use.

Short-Term Outcomes of Neonates with Hypoxic-Ischemic Encephalopathy Receiving Active Versus Passive Cooling During Transport.

Therapeutic hypothermia (TH) is the only currently approved treatment for neonatal hypoxic-ischemic encephalopathy (HIE) and must be started within 6 hours to optimize effectiveness. This narrow therapeutic window often requires initiation of TH before or during transport. The goal of this study was to assess the effects of servo-controlled TH versus passive hypothermia during transport on short-term outcomes in newborns with HIE. This was a single-center retrospective case-control study of neonates with HIE treated with active or passive TH during transport. Primary outcomes included brain injury on magnetic resonance imaging (MRI) and presence of seizures. Seventy-six neonates were included-13 active and 63 passive. The active TH group was more likely to arrive within goal temperature. No difference was noted between groups in seizures or TH complications. Active TH was associated with increased injury on MRI. Active TH resulted in tighter temperature control, but no improvement in short-term outcomes in our cohort. The MRI findings may be due to differences in overall disease severity, which could not be adjusted for, given the modest sample size.

An observational, multicenter, registry-based cohort study of Turkish Neonatal Society in neonates with Hypoxic ischemic encephalopathy

Background Hypoxic ischemic encephalopathy (HIE) is a significant cause of mortality and short- and long-term morbidities. Therapeutic hypothermia (TH) has been shown to be the standard care for HIE of infants ≥36 weeks gestational age (GA), as it has been demonstrated to reduce the rates of mortality, and adverse neurodevelopmental outcomes. This study aims to determine the incidence of HIE in our country, to assess the TH management in infants with HIE, and present short-term outcomes of these infants. Methods The Turkish Hypoxic Ischemic Encephalopathy Online Registry database was established for this multicenter, prospective, observational, nationally-based cohort study to evaluate the data of infants born at ≥34 weeks GA who displayed evidence of neonatal encephalopathy (NE) between March, 2020 and April 2022. Results The incidence of HIE among infants born at ≥36 weeks GA (n = 965) was 2.13 per 1000 live births (517:242440), and accounting for 1.55% (965:62062) of all neonatal intensive care unit admissions. The rates of mild, moderate and severe HİE were 25.5% (n = 246), 58.9% (n = 568), and 15.6% (n = 151), respectively. Infants with severe HIE had higher rates of abnormal magnetic resonance imaging (MRI) findings, and mortality (p<0.001). No significant difference in mortality and abnormal MRI results was found according to the time of TH initiation (<3 h, 3–6 h and >6 h) (p>0.05). TH was administered to 85 (34.5%) infants with mild HIE, and of those born of 34–35 weeks of GA, 67.4% (n = 31) received TH. A total of 58 (6%) deaths were reported with a higher mortality rate in infants born at 34–35 weeks of GA (OR 3.941, 95% Cl 1.446–10.7422, p = 0.007). Conclusion The incidence of HIE remained similar over time with a reduction in mortality rate. The timing of TH initiation, whether <3 or 3–6 h, did not result in lower occurrences of brain lesions on MRI or mortality. An increasing number of infants with mild HIE and late preterm infants with HIE are receiving TH; however, the indications for TH require further clarification. Longer follow-up studies are necessary for this vulnerable population.

Therapeutic hypothermia in patients after cardiac arrest: A systematic review and meta-analysis of randomized controlled trials

ObjectiveTargeted temperature management (TTM) with therapeutic hypothermia (TH) has been used to improve neurological outcomes in patients after cardiac arrest; however, several trials have reported conflicting results regarding its effectiveness. This systematic review and meta-analysis assessed whether TH was associated with better survival and neurological outcomes after cardiac arrest. MethodWe searched online databases for relevant studies published before May 2023. Randomized controlled trials (RCTs) comparing TH and normothermia in post-cardiac-arrest patients were selected. Neurological outcomes and all-cause mortality were assessed as the primary and secondary outcomes, respectively. A subgroup analysis according to initial electrocardiography (ECG) rhythm was performed. ResultNine RCTs (4058 patients) were included. The neurological prognosis was significantly better in patients with an initial shockable rhythm after cardiac arrest (RR = 0.87, 95% confidence interval [CI] = 0.76–0.99, P = 0.04), especially in those with earlier TH initiation (<120 min) and prolonged TH duration (≥24 h). However, the mortality rate after TH was not lower than that after normothermia (RR = 0.91, 95% CI = 0.79–1.05). In patients with an initial nonshockable rhythm, TH did not provide significantly more neurological or survival benefits (RR = 0.98, 95% CI = 0.93–1.03 and RR = 1.00, 95% CI = 0.95–1.05, respectively). ConclusionCurrent evidence with a moderate level of certainty suggests that TH has potential neurological benefits for patients with an initial shockable rhythm after cardiac arrest, especially in those with faster TH initiation and longer TH maintenance.

Healthcare organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort.

Initiation of therapeutic hypothermia (TH) within 6h of life is a major concern for treating neonatal hypoxic ischemic encephalopathy (HIE). We aimed to determine clinical and healthcare organizational factors associated with delayed TH in a French population-based cohort of neonates with moderate/severe HIE. Time to reach a rectal temperature of 34°C defines optimal and delayed (within and over 6h, respectively) TH. Clinical and healthcare organizational factors associated with delayed TH were analysed among neonates born in cooling centres (CCs) and non-cooling centres (non-CCs). Among 629 neonates eligible for TH, 574 received treatment (91.3%). TH was delayed in 29.8% neonates and in 20.3% and 36.2% of those born in CCs and non-CCs, respectively. Neonates with moderate HIE were more exposed to delayed TH in both CCs and non-CCs. After adjustment for HIE severity, maternal and neonatal characteristics and circumstances of birth were not associated with increased risk of delayed TH. However, this risk was 2 to 5 times higher in maternities with < 1999 annual births, when the delay between birth and call for transfer (adjusted odds ratio [aOR] 2.47, 95% confidence interval [CI] [1.03 to 5.96]) or between call for transfer and admission (aOR 6.06, 95%CI [2.60 to 14.12]) was > 3h and when an undesirable event occurred during transfer (aOR 2.66, 95%CI [1.11 to 6.37]. Conclusion: Increasing early identification of neonates who could benefit from TH and access to TH in non-CCs before transfer are modifiable factors that could improve care of neonates with HIE. Trial registration: The trial was registered at ClinicalTrials.gov (NCT02676063). What is Known: • International recommendations are to initiate therapeutic hypothermia before 6 h of life in neonates with moderate or severe hypoxic ischemic encephalopathy. What is New: •In this French population-based cohort of infants with hypoxic ischemic encephalopathy, nearly one-third of neonates eligible for treatment did not have access to hypothermia in the therapeutic window of 6 h of life. . • Among infants born in non-cooling centres, healthcare organizational factors involved in delayed care were the small size of maternities (1999 annual births), a time interval of more than 3 h between birth and call for transfer and between call for transfer and admission in neonatology, and the occurrence of an undesirable event during transfer.

Early coagulopathy after pediatric out-of-hospital cardiac arrest: secondary analysis of a randomized clinical trial

BackgroundTo estimate the incidence, risk factors, and impact on mortality and functional outcomes for early coagulopathy after the return of spontaneous circulation (ROSC) in pediatric out-of-hospital cardiac arrest (OHCA) patients.MethodsA post hoc analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial was conducted. Early coagulopathy was defined as presence of at least one of the following coagulation abnormalities upon admission: international standard ratio (INR), platelets, and age-adjusted activated partial thromboplastin time (APTT) within 6 h after OHCA and before therapeutic hypothermia initiation. The outcomes included 28-day mortality and functional prognosis. Multivariable logistic regression models were used to explore risk factors and association between early coagulopathy and outcomes.ResultsOf the 227 patients included, 152 (67%) were male and the median age was 2.3 years [interquartile range (IQR), 0.7–8.6 years]. The overall 28-day mortality was 63%. The incidence of early coagulopathy was 46%. Lower age, longer duration of chest compression, lower temperature, and higher white blood cell (WBC) upon admission increased the risk of early coagulopathy. Early coagulopathy [OR, 2.20 (95% CI, 1.12–4.39), P = 0.023] was independently associated with 28-day mortality after adjusting for confounders.ConclusionsEarly coagulopathy occurred in almost half of pediatric patients with OHCA. Lower age, longer duration of chest compression, lower temperature, and higher WBC increased the risk. The development of early coagulopathy was independently associated with increased mortality.

Short-term outcome of perinatal hypoxic-ischaemic encephalopathy at Chiang Mai University Hospital, Thailand: a 15-year retrospective study

ABSTRACT Background The outcome of perinatal hypoxic-ischaemic encephalopathy (HIE) in middle-to-low-income countries varies between regions. Objectives To determine the mortality and morbidity, and factors influencing the deaths of infants with perinatal HIE. Methods A retrospective study was conducted at Chiang Mai University Hospital, Thailand. Perinatal HIE infants of >35 weeks gestation, birthweight ≥2000 g and admitted during 2005-2019 were reviewed. Baseline Characteristics, clinical course and outcome at discharge were compared between the period before and after initiation of therapeutic hypothermia (TH). Risk of death in HIE infants who underwent TH was identified Results A total of 162 HIE infants were included. Compared to the period before TH initiation, the mortality rate was significantly decreased in the TH period. (27% vs. 12.8%, p=0.04) Among 100 HIE infants who underwent TH, the mortality rates was 14%(14/100), of whom 2.5% (2/76) and 50% (12/24) were in the moderate and severe HIE groups. Apgar score at 5 mins ≤1, severe HIE, seizures, hypoglycaemia, organ involvement ≥ five sites, ammonia ≥100 umol/L, lactate ≥14 mmol/L, and requirement for two or more inotropic drugs were risks of death. Multivariate analysis demonstrated that severe HIE (aOR 732.8, 95% CI 4.7–114643, p=0.01) and a need for two or more inotropic drugs (aOR 45.7, 95% CI 1.5–1040, p=0.029) were significant factors for mortality. Conclusion In the period of TH, perinatal HIE infants had decreased mortality. Severe HIE and a need for two or more inotropic drugs were associated with death in the infant with HIE who underwent TH. Abbreviations: AED: anti-epileptic drug; BW, birthweight; CI: confidence interval; CMU: Chiang Mai University; EEG: electro-encephalogram; GA: gestational age; HIE: hypoxic-ischaemic encephalopathy; IQR: interquartile range; NICU: neonatal intensive care unit; SD: standard deviation; TH: therapeutic hypothermia.

Comments on "Neonatal infratentorial subdural hematoma contributing to obstructive hydrocephalus in the setting of therapeutic cooling: A case report".

Although therapeutic hypothermia (TH) contributes significantly in the treatment of hypoxic ischemic encephalopathy (HIE), it could result in devastating complications such as intracranial hemorrhages. Laboratory examinations for possible coagulation disorders and early brain imaging can detect all these cases that are amenable to aggravation of HIE after the initiation of TH.

Diastolic Dysfunction in Neonates With Hypoxic-Ischemic Encephalopathy During Therapeutic Hypothermia: A Tissue Doppler Study.

Diastolic dysfunction often complicates myocardial ischemia with increased mortality rates. However, less is known about diastolic function after perinatal asphyxia in neonates with hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia (TH) and rewarming.AimThe aim of this study was to assess diastolic function with tissue Doppler imaging (TDI) in neonates with moderate–severe HIE during TH and rewarming.MethodNewborns at >36 weeks' gestation with moderate–severe HIE treated with TH were evaluated with targeted neonatal echocardiography (TNE), including TDI, within 24 h of TH initiation (T1), at 48–72 h of treatment (T2), and after rewarming (T3). These retrospective data were collected and compared with a control group of healthy babies at >36 weeks' gestation that was prospectively evaluated following the same protocol.ResultsA total of 21 patients with HIE + TH and 15 controls were included in the study. Myocardial relaxation before the onset of biventricular filling was prolonged in the HIE + TH group during TH with significantly longer isovolumic relaxation time (IVRT') in the left ventricle (LV), the septum, and the right ventricle (RV). This was associated with slower RV early diastolic velocity (e') and prolonged filling on T1. Total isovolumic time (t-IVT; isovolumic contraction time [IVCT'] + IVRT') and myocardial performance index (MPI') were globally increased in asphyxiated neonates. All these differences persisted after correction for heart rate (HR) and normalized after rewarming. TDI parameters assessing late diastole (a' velocity or e'/a' and E/e' ratios) did not differ between groups.ConclusionTDI evaluation in our study demonstrated a pattern of early diastolic dysfunction during TH that normalized after rewarming, whereas late diastole seemed to be preserved. Our data also suggest a possible involvement of impaired twist/untwist motion and dyssynchrony. More studies are needed to investigate the impact and therapeutic implication of diastolic dysfunction in these babies, as well as to clarify the role of TH in these findings.

Therapeutic Hypothermia on Transport: The Quest for Efficiency: Results of a Quality Improvement Project.

Introduction:Therapeutic hypothermia (TH) within 6 hours after birth is known to improve both survival and neurodevelopmental outcomes in neonates with hypoxic ischemic encephalopathy (HIE). Meeting this recommended target temperature for neonates who require transport for TH treatment can be complex for various reasons. This study aimed to reduce the time from birth to the initiation of TH and target temperature, thereby increasing the proportion of transported neonates reaching target temperature within 6 hours to >50%.Methods:We evaluated the effect of three quality improvement interventions, including revised transport team processes, outreach education/resources, and the use of a servo-controlled cooling device on land transports. We compared key outcome TH metrics for cohorts before and after implementation.Results:The study team compared baseline data for 77 to 102 neonates born between 2009 and April 2015 (preintervention) and September 2015 and September 2020 (postintervention(s)). We observed reductions in both the time from birth to the initiation of passive cooling (38%) and time to reach target TH temperature (23%), with an increase in the proportion of neonates reaching target temperature by 6 hours of age from 50% to 71%.Conclusions:We used quality improvement methodology to identify key areas for intervention(s) and improvement. Targeted interventions have successfully and consistently improved the timing and delivery of TH to neonates with hypoxic ischemic encephalopathy within the transport environment, with a 20% increase in neonates reaching target temperature by 6 hours of age.

Feeding during therapeutic hypothermia is safe and may improve outcomes in newborns with perinatal asphyxia

Objective We assessed the impact of early enteral feeding introduction during therapeutic hypothermia on time to reach full enteral feeding (FEF) and other feeding related outcomes in infants born at ≥35 weeks gestational age and diagnosed with moderate to severe Hypoxic-Ischemic Encephalopathy. Methods A prospective cohort with historical control study, conducted on infants admitted to the Alberta Children’s Hospital level III NICU in Calgary between January 2013 and December 2018. Infants were divided into 2 groups: (1) unfed group (UG), which was kept nil per os during the 72 h of therapeutic Hypothermia (TH), with subsequent introduction of feeding and gradual increase to FEF; (2) fed group (FG), which received feeding at 10 mL/kg/day during TH then increased gradually to FEF. Groups were compared for time to FEF and the type of milk they were being fed on discharge. Other gut related health risks such as NEC and sepsis were examined. Results During the study period, 146 infants received therapeutic hypothermia, of whom 75 in the UG and 71 in the FG. The FG compared to the UG received the first feed sooner after TH initiation (median 57 vs. 86.5 h, p < .001), reached FEF earlier (median 6 vs. 8 days, p = .012), had a higher rate of being fully fed in the first week of life (70 vs. 53%, p < .035), was kept NPO for shorter duration (median 2 vs. 4 days, p < .001), and had a higher rate of breast milk feeding at discharge (41 vs. 13%, p < .001). There were no cases of necrotizing enterocolitis or late onset sepsis in either group during the hospital stay. Conclusion Minimal enteral feeding during therapeutic hypothermia appears to be safe and leads to a shorter time to FEF and higher rates of breast milk feeding at discharge.

Process variations between Swiss units treating neonates with hypoxic-ischemic encephalopathy and their effect on short-term outcome

ObjectiveTo compare therapeutic hypothermia (TH) treatment of term and near-term neonates with hypoxic-ischemic encephalopathy (HIE) between neonatal units.Study designPopulation-based, retrospective analysis of TH initiation and maintenance, and of diagnostic imaging. The comparison between units was based on crude data analysis, indirect standardization, and adjusted logistic regression.ResultsTH was provided to 570 neonates with HIE between 2011 and 2018 in 10 Swiss units. We excluded 121 off-protocol cooled neonates to avoid selection bias. Of the remaining 449 neonates, the outcome was favorable to international benchmarks, but there were large unit-to-unit variations in baseline perinatal data and TH management. A total of 5% neonates did not reach target temperature within 7 h (3–10% between units), and 29% experienced over- or undercooling (0–38%).ConclusionAlthough the neonates had favorable short-term outcomes, areas for improvement remain for Swiss units in both process and outcome measures.

Noninvasive monitoring of evolving urinary metabolic patterns in neonatal encephalopathy.

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). 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. 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. This study shows the potential of urinary metabolic profiles for the noninvasive monitoring of brain injury of infants with NE during TH. 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.

Association of Routinely Measured Proinflammatory Biomarkers With Abnormal MRI Findings in Asphyxiated Neonates Undergoing Therapeutic Hypothermia

Background: The neuroprotective treatment effect of therapeutic hypothermia (TH) following perinatal asphyxia may be negatively influenced by neonatal sepsis and concomitant inflammation. We aimed to correlate routinely used blood biomarkers for perinatal sepsis in cooled asphyxiated newborns with MRI findings.Methods: Perinatal data was retrospectively collected from 67 cooled asphyxiated newborns. Levels of C-reactive protein (CRP), white blood cells and platelets were analyzed before, during and after TH. Interleukin-6 blood levels were analyzed before initiation of TH. Magnetic resonance imaging (MRI) on postnatal day 5–7 was used defining short-term outcome. Adverse outcome was defined as death or adverse MRI findings. Amplitude-integrated electroencephalography (aEEG) was additionally analyzed and correlated with short-term MRI outcome.Results: Forty-nine newborns had favorable short-term MRI outcome. Perinatal data referring to perinatal sepsis did not differ significantly between groups. IL-6 levels before initiation of TH and CRP levels on day three and after TH were significantly higher in newborns with adverse short-term MRI outcome. Males with adverse short-term MRI outcome had significantly increased CRP values at the end of the cooling phase. aEEG strongly correlated with short-term MRI outcome.Conclusion: Routinely used blood biomarkers may be helpful early identifying newborns at high risk of unfavorable outcome and in need of close neurodevelopmental follow-up.

Guidelines for Assessment and Initiation of Therapeutic Hypothermia (Cooling) Treatment for Moderate or Severe Hypoxic Ischaemic Encephalopathy

Aims of the Guideline To ensure that babies with suspected HIE are appropriately assessed to see whether therapeutic hypothermia (cooling) is appropriate. To ensure that cooling is initiated in a safe and timely manner. To outline the care pathway for ongoing cooling treatment.

Organ Complications of Infants with Hypoxic Ischemic Encephalopathy Before Therapeutic Hypothermia.

Hypoxic ischemic encephalopathy (HIE) is a serious neurological complication that may develop in asphyxiated infants. Severity of encephalopathy may vary, and concurrent multiorgan dysfunctions are commonly observed. Analyzing the incidence of such complications according to severity of HIE, and how they correlate with each other, may shape clinical judgment and allow for early intervention. The study included a total of 57 HIE infants, in which 27/57 (47.37%) met Sarnat inclusion criteria for moderate stage II HIE (Group A) and 30/57 (52.63%) for severe stage III HIE (Group B). Both groups were assessed and compared for incidence of kidney dysfunction, liver dysfunction, coagulopathy, qualitative cardiac abnormalities, respiratory-related dysfunction, and bone marrow insufficiency/thrombocytopenia. All assessments were performed before initiation of therapeutic hypothermia. The complications were further assessed for the presence of correlations. Group B experienced significantly higher incidence of kidney dysfunction (A: 2/27 [7.4%] vs. B: 21/30 [70%], p < 0.001), liver dysfunction (A: 14/27 [51.8%] vs. B: 28/30 [93.3%], p < 0.001), and thrombocytopenia (A: 8/27 [29.6%] vs. B 21/30 [70%], p = 0.002) in our study group. Kidney dysfunction and bone marrow insufficiency showed the highest affiliation with other organ systems in both groups, correlating positively with each other as well as HIE severity, cardiac abnormalities, liver dysfunction, and infant death. A total of 8/57 (14%) infant deaths were observed, all originating from grade III severe HIE group (p = 0.003). Multiorgan dysfunction showed a significant difference between HIE severity (A: 12/27 [44.4%] vs. B: 28/30 [93.3%], p < 0.001). A positive correlation was obtained between multiorgan dysfunction, HIE severity, and infant death. Stage III HIE infants are more likely to experience abnormalities in the kidneys, liver, bone marrow as compared with stage II HIE infants. Correlations between organ complications are present, and should be taken into account during clinical assessment of HIE infants. The probability of mortality is higher in stage III HIE infants with observed multiorgan dysfunctions.

Determinants of outcomes for acute encephalopathy with reduced subcortical diffusion

Acute encephalopathy with reduced subcortical diffusion (AED), characterised by seizure onset and widespread reduced apparent diffusion coefficient in the cortex/subcortical white matter, is one of the most common acute encephalopathies in children in East Asia. This 14-year single-centre retrospective study on 34 patients with AED showed that therapeutic hypothermia was used for patients with more severe consciousness disturbance after the first seizure or second phase initiation, extrapolating from neonatal hypoxic encephalopathy and adult post-cardiac arrest syndrome. The basal ganglia/thalamus lesions and the Tada score were the poor outcome determinants in the multivariate analysis. The correlation between the worse outcomes and the duration from the first seizure to the initiation of therapeutic hypothermia was observed only in the patients with AED cooled before the second phase. This correlation was not observed in the overall AED population. There was a moderate negative association between the worse outcomes and the duration between the first seizure and the second phase. Therefore, the basal ganglia/thalamus lesions and the Tada score were the outcome determinants for patients with AED. Further investigation is required to examine the efficacy of therapeutic hypothermia in this population while considering the timing of the therapeutic hypothermia initiation and the second phase.

Metabolic Phenotypes of Hypoxic-Ischemic Encephalopathy with Normal vs. Pathologic Magnetic Resonance Imaging Outcomes.

Hypoxic-Ischemic Encephalopathy (HIE) is one of the most relevant contributors to neurological disability in term infants. We hypothesized that clinical outcomes of newborns with (HIE) can be associated with changes at plasma metabolic level enabling the detection of brain injury. Plasma samples of a cohort of 55 asphyxiated infants who evolved to moderate/severe HIE were collected between birth and completion of therapeutic hypothermia (TH). Samples were analyzed employing a quantitative gas chromatography–mass spectrometry method for the determination of lactate and pyruvate and an untargeted liquid chromatography–time-of-flight mass spectrometry method for metabolic fingerprinting. Brain injury was assessed employing magnetic resonance imaging (MRI). A critical assessment of the usefulness of lactate, pyruvate, and pyruvate/lactate for outcome prediction was carried out. Besides, metabolic fingerprinting identified a dynamic perturbation of eleven metabolic pathways, including amino acid and purine metabolism, and the steroid hormone biosynthesis, in newborns with pathologic MRI outcomes. Although data suggest the usefulness of lactate and pyruvate monitoring during 72 h for discerning outcomes, only the steroid hormone biosynthesis pathway was significantly altered in early plasma samples (i.e., before the initiation of TH). This study highlights pathways that might potentially be targeted for biomarker discovery or adjuvant therapies to be combined with TH.

Targeted temperature management: State of the Art

One of the indicated elements of post-resuscitation care is therapeutic hypothermia or temperature treatment management. the survivability of out-of-hospital cardiac arrest (OHCA) till admission to hospital is only 23%. Efficient thermoregulatory mechanisms are the basis for maintaining optimal body temperature. Therapeutic hypothermia shows normalizing effect on metabolic processes disturbed in ischaemic conditions, including improving metabolism and maintaining glucose balance in the brain, lowering the concentration of lactates, limiting the secretion of free radicals in damaged neurons, lowering the production of pro-inflammatory cytokines, stabilizes the blood-brain barrier and reduces endothelial dysfunction preventing ischaemic damage to tissues and organs. Hypothermia has a wide multidirectional effect on the human body, which can be useful in patients. Most available scientific studies show the efficacy and benefits of hypothermia in patients with out-of-hospital sudden cardiac arrest, including especially with ventricular fibrillation. The delay in the initiation of therapeutic hypothermia and reaching target temperature significantly increased the odds of a poor neurological outcome. Current American Heart Association (AHA) and European Resuscitation Council (ERC) resuscitation guidelines recommend that targeted temperature management should be implemented in all adult coma patients with return of spontaneous circulation (ROCS) after sudden cardiac arrest. The target temperature should be between 32°C and 36°C and then maintained for at least 24 hours. In patients with coma after TTM, fever should be actively prevented. For patients with out-of-hospital cardiac arrest, it is not recommended to routinely cool patients in prehospital conditions with a rapid intravenous infusion of cold fluids after ROSC.