Introduction Of Therapeutic Hypothermia Research Articles

THERAPEUTIC HYPOTHERMIA OF NEWBORNS: RECOMMENDATIONS OF UNIVERSITÄTSKLINIKUM CARL-GUSTAV-CARUS (DRESDEN, GERMANY)

Therapeutic hypothermia (TH) is a modern standard of care for newborns with gestational age ≥36 weeks who have moderate to severe hypoxic-ischemic encephalopathy. The introduction of TH is based on evidence-based medicine, and multiple randomized controlled trials confirm its efficiency in significantly reducing the risk of death or severe infant disability. Recent practice emphasizes the vital importance of clearly defined protocols for TH and its use in neonatal care settings with facilities for multidisciplinary care and adequate resources for comprehensive monitoring and treatment.The article reports on the local protocol of TH in the neonatal intensive care unit of the University Hospital at Carl-Gustav-Carus at the Technical University Dresden (Dresden, Germany). TH is administered to newborns with moderate or severe hypoxic-ischemic encephalopathy who were born at a gestational age of ≥ 36+0 weeks, are less than 6 hours old and have no signs of massive intracranial hemorrhage. Exclusion criteria are threat to life, congenital malformations, severe intracranial hemorrhage and poor prognosis. Whole-body cooling to an internal body temperature of 33.5°C is preferred. The cooling period is 72 hours, with warming at a rate of 0.2°C per hour, followed by normothermia over the next 48 hours.Comprehensive assessment of the infant's status includes the Thompson score, amplitude and standard electroencephalography, magnetic resonance imaging, control of blood coagulation, acid-base status and blood gases, etc. Follow-up therapy is aimed at providing adequate ventilatory support to prevent hypocapnia, sufficient fluid supply, effective analgesia and anticonvulsant therapy, etc. Emphasis is placed on the need for further cathemnestic monitoring of infants who underwent TH.

Prognostic value of somatosensory-evoked potentials in the newborn with hypoxic-ischemic encephalopathy after the introduction of therapeutic hypothermia.

The present study demonstrates the good predictive capacity of SEPs performed in the first two weeks of life in newborns with HIE and TH to detect an increased risk of neuroimaging lesions and neurodevelopmental impairment at two years of age. • Bilateral absence of the N20 cortical component of somatosensory evoked potentials has been associated with poor neurological outcome in neonates with hypoxic-ischemic encephalopathy. • This work confirms the predictive capacity of SEPs by adding two important aspects: the value of latency when interpreting SEPs results and the absence of effect of the hypothermia method used on the results of SEPs.

Long-Term Outcomes after Neonatal Hypoxic-Ischemic Encephalopathy in the Era of Therapeutic Hypothermia: A Longitudinal, Prospective, Multicenter Case-Control Study in Children without Overt Brain Damage.

Background. Data on long-term outcomes in the era before therapeutic hypothermia (TH) showed a higher incidence of cognitive problems. Since the introduction of TH, data on its results are limited. Methods. Our sample population consisted of 40 children with a history of hypoxic-ischemic encephalopathy (HIE) treated with TH, with an average age of 6.25 years (range 5.5, 7.33), 24 (60%) males; and 33 peers with an average age of 8.8 years (6.08, 9.41), 17 (51%) males. Long-term follow-up data belong to two centers in Padova and Torino. We measured general intelligence (WPPSI-III or WISC-IV) and neuropsychological functioning (language, attention, memory, executive functions, social skills, visual motor abilities). We also administered questionnaires to their parents on the children’s psychopathological profiles and parental stress. Results. We found differences between groups in several cognitive and neuropsychological domains: intelligence, visuomotor skills, executive functions, and attention. Interestingly, IQ test results effectively differentiated between the groups (HIE vs. controls). Furthermore, the incidence of psychopathology appears to be significantly higher in children with HIE (35%) than in control peers (12%). Conclusions. Our study supports previous findings on a higher incidence of neuropsychological, cognitive, and psychopathological sequelae after HIE treated with TH. As hypothesized, TH does not appear to ameliorate the outcome after neonatal HIE in those children who survive without major sequelae.

Role of Optical Neuromonitoring in Neonatal Encephalopathy-Current State and Recent Advances.

Neonatal encephalopathy (NE) in term and near-term infants is a significant global health problem; the worldwide burden of disease remains high despite the introduction of therapeutic hypothermia. Assessment of injury severity and effective management in the neonatal intensive care unit (NICU) relies on multiple monitoring modalities from systemic to brain-specific. Current neuromonitoring tools provide information utilized for seizure management, injury stratification, and prognostication, whilst systemic monitoring ensures multi-organ dysfunction is recognized early and supported wherever needed. The neuromonitoring technologies currently used in NE however, have limitations in either their availability during the active treatment window or their reliability to prognosticate and stratify injury confidently in the early period following insult. There is therefore a real need for a neuromonitoring tool that provides cot side, early and continuous monitoring of brain health which can reliably stratify injury severity, monitor response to current and emerging treatments, and prognosticate outcome. The clinical use of near-infrared spectroscopy (NIRS) technology has increased in recent years. Research studies within this population have also increased, alongside the development of both instrumentation and signal processing techniques. Increasing use of commercially available cerebral oximeters in the NICU, and the introduction of advanced optical measurements using broadband NIRS (BNIRS), frequency domain NIRS (FDNIRS), and diffuse correlation spectroscopy (DCS) have widened the scope by allowing the direct monitoring of oxygen metabolism and cerebral blood flow, both key to understanding pathophysiological changes and predicting outcome in NE. This review discusses the role of optical neuromonitoring in NE and why this modality may provide the next significant piece of the puzzle toward understanding the real time state of the injured newborn brain.

Brain cooling reduces the risk of postneonatal epilepsy in newborns affected by moderate to severe hypoxic-ischemic encephalopathy.

BACKGROUND Neonatal hypoxic-ischemic encephalopathy is still a significant cause of neonatal death and neurodevelopmental disabilities, such as cerebral palsy, mental delay, and epilepsy. After the introduction of therapeutic hypothermia, the prognosis of hypoxic-ischemic encephalopathy has improved, with reduction of death and disabilities. However, few studies evaluated whether hypothermia affects rate and severity of postneonatal epilepsy. We evaluated rates, characteristics and prognostic markers of postneonatal epilepsy in infants with moderate to severe hypoxic-ischemic encephalopathy treated or not with therapeutic hypothermia. METHODS We analyzed clinical data, EEG recordings, cerebral Magnetic Resonance Imaging (MRI) and outcome in 23 cooled and 26 non-cooled asphyxiated neonates (≥36 weeks' gestation), admitted from 2004 to 2012. RESULTS Among 49 neonates 11 (22%) had postneonatal epilepsy, of which 9 (18%) were non-cooled and 2 (4%) were cooled (P=0.05). Six of 11 infants (55%) had West syndrome, 4 (36%) had focal epilepsy and 1 (9%) had Lennox-Gastaut Syndrome. At multiple logistic regression analysis MRI pattern significantly correlated with postneonatal epilepsy (OR 0.19, 95% CI 0.04-0.88, P=0.03). Extensive lesions in basal ganglia and thalami plus cortical and white matter were associated with postneonatal epilepsy. CONCLUSIONS Only perinatal asphyxia with extensive lesions in basal ganglia and thalami plus cortical and white matter lesion conveys a high risk for early and severe postneonatal epilepsy. Moreover, therapeutic hypothermia is associated with a decrease of the risk of developing postneonatal epilepsy.

Persistent pulmonary hypertension in neonates with perinatal asphyxia and therapeutic hypothermia: a frequent and perilous combination

Therapeutic hypothermia in neonates with perinatal asphyxia may increase the risk of PPHN. This potentially affects outcome. Objectives (1) To investigate whether neonates with perinatal asphyxia and therapeutic hypothermia more often developed PPHN compared to a control group with perinatal asphyxia not treated with hypothermia; (2) To identify risk factors for severe PPHN during hypothermia and evaluate short-term outcome. Methods This single-center retrospective cohort study included (near-)term neonates with perinatal asphyxia admitted between 2004 and 2016. Neonates with perinatal asphyxia and hypothermia were compared to a historical control group without hypothermia. Primary outcome was PPHN, defined as severe hypoxemia requiring mechanical ventilation and inhaled nitric oxide, confirmed by echocardiography. Short-term adverse outcome was defined as mortality within one month and/or severe brain injury on MRI. Results Incidence of PPHN was 23% (26/114) in the hypothermia group and 11% (8/70) in controls. In multivariate analysis, PPHN was 2.5 times more common among neonates with hypothermia. Neonates developing PPHN during hypothermia often had higher fraction of inspired oxygen at baseline. PPHN was not associated with a higher risk of severe brain injury. However, early mortality was higher and three infants died due to severe refractory PPHN during hypothermia. Conclusions In this study PPHN occurred more often since the introduction of therapeutic hypothermia. This was usually reversible and did not lead to overall increased adverse outcome. However, in individual cases with PPHN deterioration occurred rapidly. In such cases the benefits of hypothermia should be weighed against the risk of a complicated, fatal course.

Changes in the electrobiological activity of the brain in full-term newborns with hypoxic-ischemic encephalopathy

Early diagnosis of hypoxyc encephalopathy contributes to the timely correction of neurofunctional disorders, which reduces mortality and the severity of acute and distant neurological complications of cerebral injurie. The importance of early detection of cerebral disorders in newborns has become especially relevant with the introduction of therapeutic hypothermia in full-term infants with hypoxic encephalopathy. It has been established that with the early onset of therapeutic hypothermia, full-term neurological prognosis in the long-term period, including motor, is observed in full-term newborns. The correspondence between structural disorders and neurophysiological changes in the brain at different age periods is proved. Among the methods for the early diagnosis of cerebral injuries in newborns, the electroencephalogram is one of the leading places. The correspondence between structural disorders and neurophysiological changes in the brain at different age periods is proved. Such characteristics of the electroencephalography method as non-invasiveness, high sensitivity in assessing neurobiological activity, safety, delicacy in maintaining the stability of a critical patient, allows electroencephalography in newborns from the first hours of life. The relevance of the review is associated not only with the scattered information about changes in the electrical activity of the brain in children with hypoxic-ischemic encephalopathy in the neo. Describes the main poor prognostic EEG patterns in the form of a suppression rate (decrease in the amplitude with the maximum manifestation of the oppression of the electrobiological activity in the form of a pattern burst suppression), slowing of the basic rhythm, rarely revealed epileptic, epileptiform activity, focal sharp activity. Such characteristics of the electroencephalography method as non-invasiveness, high sensitivity in assessing neurobiological activity, safety, delicacy in maintaining the stability of a critical patient, allows electroencephalography in newborns from the first hours of life. The relevance of the review is associated not only with the scattered information about changes in the electrical activity of the brain in children with hypoxic-ischemic natal period, but also with the peculiarity of brain electrogenesis during the neonatal period.

Results of the hypothermia registry of the University Hospital Dresden from 2010-2017. Application of hypothermia therapy in newborns in Germany

Therapeutic hypothermia (TH) improves the outcome in newborns with hypoxic-ischemic encephalopathy (HIE) and should be used in case of perinatal asphyxia and signs of moderate/severe HIE. Frequency of HIE and the application of TH were extracted from the neonatal survey, a registry that collects data from all German hospitals, and from the hypothermia registry, established in 2010. The latter was also used to analyze short-term outcomes of the newborns. Between 2010 and 2017, 106 of Germany's 213 perinatal centers joined the registry. Response rates varied between 22 and 60%. The registry recorded 164 (IQR 115-224) TH cases per year in newborns with HIE. In the neonatal survey, 517 (382-664) TH and 543 (432-581) HIE cases were reported. Since 2014 there have been more cases of TH than HIE. After TH, 10.4% (8-13%) of the newborns died, 81% (78-82%) of the newborns were discharged home, 3.6% (3-5%) to a rehabilitation facility, and 5.4% (5-7%) transferred to another clinic. 89% (87-89%) were on complete oral feedings. After the introduction of TH in the clinical routine, the number of treated newborns increased continuously. Currently, the number of TH is higher than the number of children with HIE, which is difficult to explain, as the presence of a moderate or severe HIE is a mandatory requirement for TH. The data from the hypothermia registry showed no significant changes in mortality or neurological outcome over time.

Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis

Introduction: Prediction of neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy remains an important challenge. Various studies have shown that the predictive ability of different modalities changed after the introduction of therapeutic hypothermia. This paper reviews the diagnostic test accuracy of the different modalities that are being used to predict neurodevelopmental outcomes following therapeutic hypothermia. Methods: A systematic literature search was performed using Embase and PubMed. Two reviewers independently included eligible studies and extracted data. The quality of the studies was assessed using the Quality in Prognosis Studies Tool. Meta-analyses were performed where possible. Results: Forty-seven articles and 3 conference abstracts were included, reporting on 3,072infants of whom 39% died or had an adverse neurodevelopmental outcome. A meta-analysis could be performed using 37 articles on (amplitude-integrated) electroencephalography (EEG), conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and proton magnetic resonance spectroscopy (¹H-MRS). Amplitude-integrated EEG (aEEG) at 24 and 72 h showed similar high diagnostic OR, while aEEG at 6 h and EEG performed less, both due to a low specificity. For MRI, most studies reported scoring systems in which early (<8 days) MRI performed better than late (≥8 days) MRI. Injury to the posterior limb of the internal capsule on MRI or to the thalami on DWI were strong individual predictors, as was an increased lactate/N-acetylaspartate peak on ¹H-MRS. Conclusions: In the era of therapeutic hypothermia, the different modalities remain good predictors of neurodevelopmental outcome. However, timing should be taken into account. aEEG may initially be false positive and gets more reliable after 24 h. In contrast, MRI should be used during the first week, as its predictive value decreases afterwards.

Maternal risk factors for adverse outcome in asphyxiated newborns treated with hypothermia: parity and labor duration matter

Introduction Perinatal asphyxia remains a frequent cause of neonatal mortality and long-term neurodevelopmental sequelae, despite the introduction of therapeutic hypothermia. Specific maternal characteristics may predispose asphyxiated newborns treated with hypothermia to worse outcome. Objective To investigate the possible association between specific maternal factors and adverse outcome in asphyxiated newborns treated with hypothermia. Methods We conducted a retrospective review of our database of 215 asphyxiated newborns treated with hypothermia from 2008 to 2015. We collected maternal characteristics including parity and labor duration, and we defined adverse outcome as death and/or brain injury. We compared the maternal characteristics between the asphyxiated newborns who developed adverse outcome and those who did not. Results Asphyxiated newborns born to nulliparous mothers had a significantly higher risk of adverse outcome (61%), compared to asphyxiated newborns born from primiparous (19%) and multiparous (20%) mothers (p = .002). Labor duration was longer in nulliparous mothers (p = .04). Among mothers who delivered vaginally, labor duration was significantly longer in newborns developing adverse outcome (p = .04). In multivariable analysis, parity was confirmed as an independent predictor of adverse outcome in all newborns, but labor duration showed a borderline non-significant association with adverse outcome (p = .051) only in newborns born vaginally. Labor duration beyond 12 h of life was associated with maximal sensitivity and specificity in detecting asphyxiated newborns at an increased risk of adverse outcome despite hypothermia treatment (AUC 0.62, p = .044). Conclusions Newborns with evidence of perinatal asphyxia, born to nulliparous mothers, and especially to those in whom the duration of labor has been prolonged, might be at higher risk of death or brain injury despite the use of therapeutic hypothermia.

Effects of therapeutic hypothermia on cerebral tissue oxygen saturation in a swine model of post-cardiac arrest.

Since the introduction of therapeutic hypothermia (TH), trends have changed in the monitoring indicators used during and after cardiac arrest. During hypothermia, the cerebral metabolic rate of oxygen is reduced, which leads to uncertainty in regional cerebral tissue oxygen saturation (SctO2). The aim of the present study was to evaluate the effect of TH on changes in SctO2 using near-infrared spectroscopy. A total of 23 male domestic pigs were randomized into three groups: TH (n=9), normothermia (NT; n=9) and control (n=5). Animals in the control group underwent surgical preparation only. The animal models were established using 8 min of ventricular fibrillation and 5 min of cardiopulmonary resuscitation. In the TH group, at 5 min after resuscitation, the animals were cooled with a cooling blanket and ice packs for 24 h. SctO2 was recorded throughout the experiment. In all groups, The mean arterial pressure, arterial carbon dioxide partial pressure, arterial oxygen partial pressure, lactate, neuron-specific enolase (NSE) and S100B were measured at baseline and at 1, 3, 6, 12, 24 and 30 h after resuscitation. SctO2 significantly decreased after ventricular fibrillation, compared with the baseline. Following resuscitation, the SctO2 values gradually increased to 55.6±3.8% of baseline in the TH group and 51.2±3.5% in the NT group (P=0.039). Significant differences between the two groups were observed, starting at 6 h after cardiac arrest. Throughout the hypothermic period, NSE and S100B showed an increasing trend, then decreased during rewarming in the TH and NT groups. NSE and S100B showed greater improvement in the TH group compared with the NT group at 6 and 24 h after resuscitation. Following cardiac arrest, therapeutic hypothermia could increase SctO2 after resuscitation and could improve neurological outcome. In conclusion, SctO2 may be a feasible marker for use in the early assessment of brain damage during and after cardiac arrest.

Impact of therapeutic hypothermia on infantile spasms: an observational cohort study.

AimTo establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic‐ischemic encephalopathy (HIE).MethodChildren born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome.ResultsForty‐two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1–40.0wks]). The aetiology for infantile spasms was identified in almost two‐thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138).InterpretationThis study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants.What this paper adds The incidence of infantile spasms and patient characteristics in the southern region of the Republic of Ireland is similar to internationally published data.None of the infants with a history of mild hypoxic‐ischemic encephalopathy (HIE) developed infantile spasms.The risk of infantile spasms was higher in infants with severe HIE.Infantile spasms were more frequent in infants with severe HIE not treated with therapeutic hypothermia.

Brain cooling reduces the risk of postneonatal epilepsy in newborns affected by moderate to severe hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic encephalopathy is still a significant cause of neonatal death and neurodevelopmental disabilities, such as cerebral palsy, mental delay, and epilepsy. After the introduction of therapeutic hypothermia, the prognosis of hypoxic-ischemic encephalopathy has improved, with reduction of death and disabilities. However, few studies evaluated whether hypothermia affects rate and severity of postneonatal epilepsy. We evaluated rates, characteristics and prognostic markers of postneonatal epilepsy in infants with moderate to severe hypoxic-ischemic encephalopathy treated or not with therapeutic hypothermia. We analyzed clinical data, EEG recordings, cerebral Magnetic Resonance Imaging (MRI) and outcome in 23 cooled and 26 non-cooled asphyxiated neonates (≥36 weeks' gestation), admitted from 2004 to 2012. Among 49 neonates 11 (22%) had postneonatal epilepsy, of which 9 (18%) were non-cooled and 2 (4%) were cooled (P=0.05). Six of 11 infants (55%) had West syndrome, 4 (36%) had focal epilepsy and 1 (9%) had Lennox-Gastaut Syndrome. At multiple logistic regression analysis MRI pattern significantly correlated with postneonatal epilepsy (OR 0.19, 95% CI 0.04-0.88, P=0.03). Extensive lesions in basal ganglia and thalami plus cortical and white matter were associated with postneonatal epilepsy. Only perinatal asphyxia with extensive lesions in basal ganglia and thalami plus cortical and white matter lesion conveys a high risk for early and severe postneonatal epilepsy. Moreover, therapeutic hypothermia is associated with a decrease of the risk of developing postneonatal epilepsy.

Epilepsy Outcome in Cooled Hypoxic–Ischemic Encephalopathic Newborns

AbstractEpilepsy is a frequent consequence of neonatal hypoxic–ischemic encephalopathy. It is not yet known if the introduction of therapeutic hypothermia modifies the rate and the characteristics of epilepsy. We report on 59 infants who suffered from hypoxic–ischemic encephalopathy and underwent therapeutic hypothermia. Birth, physiological and biochemical data, frequent electroencephalography (EEG) recordings or continuous EEG monitoring, and magnetic resonance imaging (MRI) were documented in the neonatal period. Prechtl's General Movements evaluation was performed and the Griffiths Scales of Mental Development were applied at 3 and 24 months of age, respectively. Children were followed up for at least 3 years (mean 5 ± 1.6 years). Six children (10%) developed epilepsy. All of them had a severe hypoxic–ischemic encephalopathy and were neurologically impaired at 2 years of age. Furthermore, all of them had a severe pattern of MRI injury and poor neonatal EEG backgrounds. Four of them suffered from neonatal status epilepticus. Four out of six showed a similar epileptic pattern: their epilepsy started early; it was drug resistant; it required an aggressive polytherapy; and it showed a spontaneous improvement after 2 years. The rate of epilepsy in our cooled infants was similar to those reported in other studies on noncooled ones. Only severe hypoxic–ischemic encephalopathy predisposed the cooled infants toward epilepsy. Neonatal status epilepticus and persisting poor EEG backgrounds were predictive of the development of epilepsy in our sample.

Heart rate variability in hypoxic ischemic encephalopathy during therapeutic hypothermia.

Therapeutic hypothermia (TH) aims to ameliorate further injury in infants with moderate and severe hypoxic ischemic encephalopathy (HIE). We aim to assess the effect of TH on heart rate variability (HRV) in infants with HIE. Multichannel video-electroencephalography (EEG) and electrocardiography were assessed at 6-72 h after birth in full-term infants with HIE, recruited prior to (pre-TH group) and following (TH group) the introduction of TH in our neonatal unit. HIE severity was graded using EEG. HRV features investigated include: mean NN interval (mean NN), standard deviation of NN interval (SDNN), triangular interpolation (TINN), high-frequency (HF), low-frequency (LF), very low-frequency (VLF), and LF/HF ratio. Linear mixed model comparisons were used. 118 infants (pre-TH: n = 44, TH: n = 74) were assessed. The majority of HRV features decreased with increasing EEG grade. Infants with moderate HIE undergoing TH had significantly different HRV features compared with the pre-TH group (HF: P = 0.016, LF/HF ratio: P = 0.006). In the pre-TH group, LF/HF ratio was significantly different between moderate and severe HIE grades (P = 0.002). In the TH group, significant differences were observed between moderate and severe HIE grades for SDNN: P = 0.020, TINN: P = 0.005, VLF: P = 0.029, LF: P = 0.010, and HF: P = 0.006. The HF component of HRV is increased in infants with moderate HIE undergoing TH.

Hypoxic-Ischemic Encephalopathy and Therapeutic Hypothermia: The Hemodynamic Perspective

Hypoxic-ischemic encephalopathy (HIE) is a severe central nervous system injury in neonates secondary to perinatal asphyxia. It may cause devastating lifelong neurocognitive impairments including cerebral palsy. The introduction of therapeutic hypothermia (TH) as standard therapy for neonates >36 weeks gestational age with HIE has improved patient outcomes and is supported by evidence from both animal studies and large-scale clinical trials in humans. TH has been shown to produce clinically important improvements in both neonatal mortality (number needed to treat = 11) and neurodevelopmental impairment in survivors (number needed to treat = 8) in patients with moderate or severe encephalopathy. 1 Jacobs S.E. Berg M. Hunt R. Tarnow-Mordi W.O. Inder T.E. Davis P.G. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013; (CD003311) Crossref Scopus (390) Google Scholar Although this intervention is the standard of care in many institutions, the rates of death or neurodevelopmental impairment are approximately 45%-55% despite optimal application of TH 1 Jacobs S.E. Berg M. Hunt R. Tarnow-Mordi W.O. Inder T.E. Davis P.G. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013; (CD003311) Crossref Scopus (390) Google Scholar ; reasons for this disparity remain elusive. The relative contribution of hemodynamic instability or treatment for it to the injurious process remains poorly understood; most clinicians “feel” a compulsion to treat presumed low blood pressure or low cardiac output based on traditional viewpoints. Multiorgan dysfunction is common 2 Shah P. Riphagen S. Beyene J. Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2004; 89: F152-5 Crossref PubMed Scopus (239) Google Scholar and cardiovascular dysfunction, defined as either evidence of transient myocardial ischemia or hypotension requiring an inotrope >24 hours, is noted in 62% of neonates with a diagnosis of HIE. 2 Shah P. Riphagen S. Beyene J. Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2004; 89: F152-5 Crossref PubMed Scopus (239) Google Scholar

Biochemical Derangements in Patients with Hypoxic Ischemic Encephalopathy Treated With Therapeutic Hypothermia

Abstract BACKGROUND: Therapeutic hypothermia is the standard of care for treating moderate or severe hypoxic ischemic encephalopathy (HIE) due to birth asphyxia. During the cooling period, altered intermediary metabolism coupled with multi-organ injury due to the underlying hypoxia may result in significant metabolic and biochemical derangements. Since the introduction of therapeutic hypothermia we have noticed an apparent increase in hyperglycemia and hyponatremia though such has not been formally documented. OBJECTIVES: This study sought to determine if there is a difference in the incidence of biochemical derangements in patients undergoing therapeutic hypothermia for moderate to severe HIE compared to a historical control group receiving standard supportive care. DESIGN/METHODS: A retrospective chart review was performed with a cluster sampling technique to select all patients ≥35 weeks PMA with a primary admission diagnosis of HIE in the years 2006, 2009, and 2012 at a single institution. This covered a time period before therapeutic hypothermia was established as standard of care, when it was in its implementation phase, and once fully established. Other than the hypothermia itself, there were no major changes in management of these patients, particularly, no change in fluid management regimens. Gestational age, birth weight, APGARs, severity of HIE, medications, blood glucose, electrolytes, liver and renal function were collected retrospectively at all time points during the 72 hour cooling window. Analysis was performed using unpaired students ttest using 0.05 as a definition of statistical significance. RESULTS: 155 patients were identified, 20 were excluded due to gestational age or suspected/confirmed underlying genetic disorder leaving n=60 cooled neonates and n=75 uncooled. The average gestational age in the cooled group was 39 and 3/7 weeks and in the uncooled group it was 38 and 5/7 weeks. In both groups, there were slightly more males than females with 57% (n=34) in the cooled group and 59% (n=44) in the uncooled group. There is a statistically significant increase in plasma glucose in the cooled group on day one (7.37±1.73 vs. 5.49±1.89, P&amp;lt;0.01) and day two (6.26±1.61 vs 5.34±1.79, P &amp;lt;0.05). There was no difference on day three. Serum sodium was lower in the cooled group on all three days, though it was only statistically significant on day 1 (130.29±4.84 vs. 132.27±4.58, P&amp;lt;0.05). CONCLUSION: Our results suggest that without significant changes in fluid management, therapeutic hypothermia is associated with an increased incidence of hyperglycemia and hyponatremia. Further work is needed to determine if these derangements significantly affect short or long-term outcomes.

79. Status epileptics and myoclonus in comatose patients after cardiac arrest: To treat or not to treat

Status epilepticus and myoclonus are common in comatose patients after cardiac arrest (Krumholz et al., 1988; Young et al., 1990). There is no consensus on when and for how long to treat this condition. This point became more relevant after introduction of therapeutic hypothermia (TH) because of some patients with MS treated with TH recovered consciousness (Rossetti et al., 2009). We propose a treatment protocol based on clinical-EEG features and somatosensory evoked potentials (SEPs) as prognostic indicator. In patients with absent SEPs we do not treat aggressively with AED considering the poor outcome. In patients with preserved SEPs we treat myoclonus if associated with GPEDs, convulsive status epilepticus and non convulsive status epilepticus (Beniczky et al., 2013). We use a combination of AED (valproate, levetiracetam) with sedation (propofol or midazolam). We present two representative cases in which we describe in more detail our therapeutic approach.

2: Renal Haemodynamics and Acute Kidney Injury During Therapeutic Hypothermia and Re-Warming in Neonates with Hypoxic-Ischaemic Encephalopathy

Birth asphyxia is associated with acute kidney injury (AKI); severity may correspond with degree of hypoxia. Previous work by our group demonstrated lower cardiac output in neonates undergoing therapeutic hypothermia (TH). The relevance of these changes to AKI remains unknown. To describe longitudinal renal haemodynamic changes during TH and re-warming (RW) and evaluate their relationship with cardiac output in neonates with and without AKI. Prospective observational study of 18 term and near-term infants with hypoxic-ischaemic encephalopathy (HIE) who received TH. Doppler ultrasound was used to assess left ventricular output (LVO) and renal artery (RA) blood flow parameters – systolic and end-diastolic velocity (Vs and Vd), and resistive index (RI) during cooling [TH I (24 h) and II (72 h)] and post re-warming [RW I (12 h) and II (>24 h)]. AKI was defined as anuria/oliguria (100 mmol/L; or anuria/oliguria for >36 h; or any serum creatinine >125 mmol/L; or rising serum creatinine postnatally. There was no difference in baseline demographics or severity of HIE between neonates with (n=8) vs without (n=10) AKI. All 18 infants survived till discharge. Neonates who developed AKI had higher RA RI 24 h after TH was initiated [Table 1]. There was a temporal increase in LVO in both groups (P<0.01, two-way ANOVA), without intergroup difference. Neonates in the non-AKI group only showed an increase in RI (P=0.01) and a trend towards increase in RA Vs over time (P=0.05). Early changes in end-diastolic flow (EDF) were seen in both groups, which normalized over time. Elevated RA RI at 24 h after introduction of TH is associated with and predicts AKI. The fall in cardiac output and renal systolic flow after TH is not associated with AKI.

Use of bispectral index EEG monitoring for a fast and reliable detection of epileptic activity in postcardiac arrest patients

Assessment of prognosis in postcardiac arrest (post-CA) patients became very challenging since the Introduction of therapeutic hypothermia (TH). Continuous EEG monitoring has been proposed to improve prognostication; however, its use is limited due to difficulties in ready interpretation. Thus emerges the need for a simple EEG montage. The bispectral index (BIS) monitor is a simplified EEG system, mainly calculating an index ranging from 0 (isoelectric EEG) to 100 (full consciousness) to provide information on hypnotic depth of anaesthesia. The aim of the study was to validate the accuracy of simplified EEG monitoring in a CA setting.