Technical feasibility of using auditory phase-targeted stimulation after pediatric severe traumatic brain injury in an intensive care setting.

BACKGROUND: Supplementary treatment options after pediatric severe traumatic brain injury (TBI) are needed to improve neurodevelopmental outcome. Evidence suggests enhancement of brain delta waves via auditory phase-targeted stimulation might support neuronal reorganization, however, this method has never been applied in analgosedated patients on the pediatric intensive care unit (PICU). Therefore, we conducted a feasibility study to investigate this approach: In a first recording phase, we examined feasibility of recording over time and in a second stimulation phase, we applied stimulation to address tolerability and efficacy. METHODS: Pediatric patients (> 12 months of age) with severe TBI were included between May 2019 and August 2021. An electroencephalography (EEG) device capable of automatic delta wave detection and sound delivery through headphones was used to record brain activity and for stimulation (MHSL-SleepBand version 2). Stimulation tolerability was evaluated based on report of nurses, visual inspection of EEG data and clinical signals (heart rate, intracranial pressure), and whether escalation of therapy to reduce intracranial pressure was needed. Stimulation efficacy was investigated by comparing EEG power spectra of active stimulation versus muted stimulation (unpaired t-tests). RESULTS: In total, 4 out of 32 TBI patients admitted to the PICU (12.5%) between 4 and 15 years of age were enrolled in the study. All patients were enrolled in the recording phase and the last one also to the stimulation phase. Recordings started within 5 days after insult and lasted for 1-4 days. Overall, 23-88 h of EEG data per patient were collected. In patient 4, stimulation was enabled for 50 min: No signs of patient stress reactions were observed. Power spectrums between active and muted stimulation were not statistically different (all P > .05). CONCLUSION: Results suggests good feasibility of continuously applying devices needed for auditory stimulation over multiple days in pediatric patients with TBI on PICU. Very preliminary evidence suggests good tolerability of auditory stimuli, but efficacy of auditory stimuli to enhance delta waves remains unclear and requires further investigation. However, only low numbers of severe TBI patients could be enrolled in the study and, thus, future studies should consider an international multicentre approach.

Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy - an 11-year single-center experience.

OBJECTIVES: Although neonates with moderate to severe hypoxic ischemic encephalopathy (HIE) receive therapeutic hypothermia (TH), 40-50% die or have significant neurological disability. The aim of this study is to analyse the association of placental pathology and neurodevelopmental outcome in cooled neonates with HIE at 18-24 months of age. METHODS: Retrospective analysis of prospectively collected data on 120 neonates registered in the Swiss National Asphyxia and Cooling Register born between 2007 and 2017. This descriptive study examines the frequency and range of pathologic findings in placentas of neonates with HIE. Placenta pathology was available of 69/120 neonates, whose results are summarized as placental findings. As neonates with HIE staged Sarnat score 1 (21/69) did not routinely undergo follow-up assessments and of six neonates staged Sarnat Score 2/3 no follow-up assessments were available, 42/48 (88%) neonates remain to assess the association between placental findings and outcome. RESULTS: Of the 42/48 (88%) neonates with available follow up 29% (12/42) neonates died. Major placenta abnormalities occurred in 48% (20/42). Major placenta abnormality was neither associated with outcome at 18-24 months of age (OR 1.75 [95% CI 0.50-6.36, p=0.381]), nor with death by 2 years of age (OR 1.96 [95% CI 0.53-7.78, p=0.320]). CONCLUSIONS: In this study cohort there could not be shown an association between the placenta findings and the neurodevelopmental outcome at 18-24 months of age.

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency.

BACKGROUND: Recognition of viral nucleic acids is one of the primary triggers for a type I interferon-mediated antiviral immune response. Inborn errors of type I interferon immunity can be associated with increased inflammation and/or increased susceptibility to viral infections as a result of dysbalanced interferon production. NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. The role of ZNFX1 in the human immune response is not known. OBJECTIVE: We studied 15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic lymphohistiocytosis-like disease, early-onset seizures, and renal and lung disease. METHODS: Whole exome sequencing was performed on 13 patients from 8 families. We investigated the transcriptome, posttranscriptional regulation of interferon-stimulated genes (ISGs) and predisposition to viral infections in primary cells from patients and controls stimulated with synthetic double-stranded nucleic acids. RESULTS: Deleterious homozygous and compound heterozygous ZNFX1 variants were identified in all 13 patients. Stimulation of patient-derived primary cells with synthetic double-stranded nucleic acids was associated with a deregulated pattern of expression of ISGs and alterations in the half-life of the mRNA of ISGs and also associated with poorer clearance of viral infections by monocytes. CONCLUSION: ZNFX1 is an important regulator of the response to double-stranded nucleic acids stimuli following viral infections. ZNFX1 deficiency predisposes to severe viral infections and a multisystem inflammatory disease.

Treatment of Catheter-Related Arterial Thrombosis in Children: A 15-Year Single- Center Experience.

OBJECTIVE: To investigate treatment modalities for children with extremity indwelling catheter (EIC)- or cardiac catheter-related arterial thrombosis. STUDY DESIGN: The treatment of consecutive cases of catheter-related arterial thrombosis (CAT) at our institution between 2002 and 2017 was analyzed retrospectively. RESULTS: A total of 242 CATs developed in 224 children. Of these, 125 (52%) were EIC-related and 117 (48%) were cardiac catheter-related. Treatment included heparin alone in 60 cases (25%), acetylsalicyclic acid (ASA) alone in 6 cases (2%), heparin followed by ASA in 171 cases (71%), heparin followed by vitamin K antagonist (VKA) in 4 cases (1.5%), and VKA alone in 1 case (0.5%). Complete resolution of CAT was observed in 173 cases (71.5%), partial resolution in 13 cases (5.4%), and no resolution in 56 cases (23.1%). No statistical significance in the resolution rate was observed between treatment groups (P = .23). In 66% of cases, complete resolution occurred at a median of 18 days (range, 4-44 days) with heparin alone. A switch from heparin to ASA in children with partial or no resolution of CAT did not increase the resolution rate at follow-up. CONCLUSIONS: Heparin is an efficient treatment modality for CAT in pediatric patients. Long-term, subsequent treatment with ASA does not increase the resolution rate.

Risk Factors for Postprocedural Arterial Ischemic Stroke in Children With Cardiac Disease.

BACKGROUND AND PURPOSE: Cardiac pathologies are the second most frequent risk factor (RF) in children with arterial ischemic stroke (AIS). This study aimed to analyze RFs for AIS in children with cardiac disease and cardiac intervention. METHODS: Data were drawn from the Swiss Neuropediatric Stroke Registry. Patients with cardiac disease and postprocedural AIS registered from 2000 until 2015 were analyzed for the cause of cardiac disease and for potential RFs. RESULTS: Forty-seven out of 78 children with cardiac disease had a cardiac intervention. Of these, 36 presented a postprocedural AIS. Median time from cardiac intervention to symptom onset was 4 days (interquartile range, 2-8.5); time to diagnosis of AIS was 2 days (interquartile range, 0-5.8). Main RFs for postprocedural AIS were hypotension, prosthetic cardiac material, right-to-left shunt, arrhythmias, low cardiac output, and infections. CONCLUSIONS: In children with postprocedural AIS, time to diagnosis was delayed. Most patients presented multiple potentially modifiable RFs as hemodynamic alterations and infections.

Short-term neurological improvement in neonates with hypoxic-ischemic encephalopathy predicts neurodevelopmental outcome at 18-24 months.

Objectives To evaluate the association of short-term neurological improvement until day of life 4 in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with neurodevelopmental outcome at 18-24 months. Methods This is a retrospective analysis of prospectively collected data of 174 neonates with HIE registered in the Swiss National Asphyxia and Cooling Register between 2011 and 2013. TH was initiated according to national guidelines, and Sarnat staging was performed daily. Short-term neurological improvement was defined if Sarnat stage improved from admission until day 4 of life. Standardized neurodevelopmental assessments were performed at 18-24 months. Unfavorable outcome was defined as death before 2 years of age or severe or moderate disability at follow-up. Results One hundred and sixty-four of 174 neonates (94%) received TH, of those 30 (18%) died in the neonatal period (no late mortality). Eighty-one percent of the survivors (109/134) were seen at 18-24 months. Of the 164 cooled neonates, 62% had a short-term neurological improvement, and the Sarnat score remained unchanged in 33%. Short-term neurological improvement was associated with an odds ratio (OR) of 0.118 [95% confidence interval (CI) 0.051-0.271] for an unfavorable outcome at 18-24 months. Conclusion Short-term neurological improvement predicts neurodevelopmental outcome at 18-24 months in the era of TH. Clinical examination must be part of a comprehensive evaluation for prognostication in HIE.

Abdominal compartment syndrome and decompressive laparotomy in children: a 9-year single-center experience.

PURPOSE: Abdominal compartment syndrome (ACS) in children results in 100% mortality if left untreated. Decompressive laparotomy (DL) is the only effective treatment if conservative medical therapies have failed. This study aims to determine the incidence of ACS among pediatric patients who underwent an emergency laparotomy (EL), to describe the effect of DL on clinical and laboratory parameters and, to make a better prediction on fatal outcome, to analyze variables and their association with mortality. METHODS: This retrospective study includes 418 children up to the age of 16 years who underwent EL between January 2010 and December 2018 at our tertiary pediatric referral center. ACS was defined according to the latest guidelines of the World Society of the Abdominal Compartment Syndrome. RESULTS: Fourteen patients had emergency DL for ACS. 6 h preoperatively; median intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) were 22.5 mmHg and 29 mmHg, respectively. After DL, IAP decreased and APP increased, both by an average of 60%. Six patients survived, eight patients had a fatal outcome, resulting in a mortality of 57%. An age under 1 year, weight under the 3rd percentile, an open abdomen treatment, an intestinal resection and an elevated serum lactate > 1.8 mmol/L were associated with an increased relative risk of death. CONCLUSIONS: Improving the outcome in pediatric patients with ACS by removing or attenuating risk factors is difficult. This emphasizes the need for early diagnosis and prompt DL once the diagnosis of ACS is made.

Video Recordings to Analyze Preventable Management Errors in Pediatric Resuscitation Bay.

OBJECTIVE: In treating patients of different ages and diseases in the pediatric resuscitation bay, management errors are common. This study aimed to analyze the adherence to advanced trauma life support and pediatric advanced life support guidelines and identify management errors in the pediatric resuscitation bay by using video recordings. METHODS: Video recording of all patients admitted to the pediatric resuscitation bay at University Children's Hospital Zurich during a 13-month period was performed. Treatment adherence to advanced trauma life support guidelines and pediatric advanced life support guidelines and errors per patient were identified. RESULTS: During the study period, 128 patients were recorded (65.6% with surgical, 34.4% with medical diseases). The most common causes for admission were traumatic brain injury (21.1%), multiple trauma (20.3%), and seizures (14.8%). There was a statistically significant correlation between accurate handover from emergency medical service to hospital physicians and adherence to airway, breathing, circulation, and disability sequence (correlation coefficient [CC], 0.205; P = 0.021), existence of a defined team leader and adherence to airway, breathing, circulation, and disability sequence (CC, 0.856; P < 0.001), and accurate hand over and existence of a defined team leader (CC, 0.186; P = 0.037). Unexpected errors were revealed. Cervical spine examination/stabilization was omitted in 40% of admitted surgical patients, even in 20% of patients with an injury of spine/limbs. CONCLUSIONS: Video recording is a useful tool to evaluate patient management in the pediatric resuscitation bay. Analyzing errors of missing the adherence to the guidelines helps to pay attention and focus on specific items to improve patient care.

Transthoracic intracardiac catheters in pediatric cardiac patients: A single-center experience.

BACKGROUND: Transthoracic intracardiac catheters are frequently inserted in children during congenital heart surgery for monitoring and vascular access purposes. Their use entails a small potential risk. AIM: We aimed to evaluate both catheter-associated morbidities related to maintenance and removal of transthoracic intracardiac catheters in pediatric cardiac patients, and predictors for catheter-associated adverse events. METHODS: Single-center retrospective cohort study of prospectively collected data of children aged 0-14 years receiving a transthoracic intracardiac catheter inserted in the operating room during 7 consecutive years at the University Children's Hospital Zurich. RESULTS: A total of 115 transthoracic intracardiac catheters were placed in 112 patients: 45 right atrial, 68 left atrial, and 2 pulmonary artery catheters. Five catheters (4.3%) had to be removed due to catheter-associated adverse events (infection, 2; nonfunction, 2; and leakage 1). After catheter removal, 19% of patients suffered adverse events, these were minor in 16 (14%) and serious in 6 (5.1%) (symptomatic bleeding in four (3.5%) patients, pericardial tamponade leading to death in one (0.8%), and tension pneumothorax in one (0.8%)). Catheter position in the right atrium and the need for platelet transfusion prior to removal were risk factors for adverse events. CONCLUSIONS: Transthoracic intracardiac catheters are useful in the management of specific patient groups with complex congenital heart defects. Adverse events do occur; most of them do not require intervention. The insertion technique plays an important role in avoiding adverse events. Strict guidelines for the use and removal of transthoracic intracardiac catheters are required. Low platelet count should delay catheter removal. The wealth of information and therapeutic options offered by these catheters appear to outweigh the associated potential adverse events in this specific patient group.

Postoperative Amplitude-Integrated Electroencephalography Predicts Four-Year Neurodevelopmental Outcome in Children with Complex Congenital Heart Disease.

OBJECTIVES: To evaluate the predictive value of pre- and postoperative amplitude-integrated electroencephalography (aEEG) on neurodevelopmental outcomes in children operated for congenital heart disease (CHD). STUDY DESIGN: Prospectively enrolled cohort of 60 infants with CHD who underwent cardiac surgery with cardiopulmonary bypass in the first 3 months of life. Infants with a genetic comorbidity were excluded. aEEG was assessed for 12 hours pre- and 48 hours postoperatively. Background pattern was classified by the use of standard categories, and the presence of seizures and sleep-wake cycles (SWCs) was noted. Outcome at 1 and 4 years of age was assessed with standardized developmental tests. RESULTS: Preoperatively, infants either showed continuous normal voltage (n = 56) or discontinuous normal voltage (n = 4). Postoperatively, abnormal background pattern (flat trace, burst suppression, or continuous low voltage) was detected in 7 (12%), discontinuous normal voltage in 37 (61%), and continuous normal voltage in 16 (27%) infants. Nineteen infants (32%) did not return to normal SWCs within the recording period. Seizures were detected in 4 infants preoperatively and in another 4 postoperatively. After we controlled for surgical and postoperative risk factors, abnormal postoperative background pattern and lack of return to SWCs independently predicted poorer intelligence quotient at 4 years (P = .03 and P = .04 respectively) but was not related to motor outcome. CONCLUSION: aEEG is a useful bedside tool that helps to predict outcome in infants undergoing open-heart surgery for CHD. Abnormal postoperative background pattern and lack of return to SWCs are markers for subsequent impaired cognitive development.

Long-Term Outcome of Catheter-Related Arterial Thrombosis in Infants with Congenital Heart Disease.

OBJECTIVES: To investigate the long-term outcome of catheter-related arterial thrombosis in children. STUDY DESIGN: Data from clinical and radiologic long-term follow-up of infants with congenital heart disease developing arterial thrombosis following femoral catheterization are presented. RESULTS: Ninety-five infants with radiologically proven arterial thrombosis because of cardiac catheter (n = 52; 55%) or indwelling arterial catheter (n = 43; 45%) were followed for a median time of 23.5 months (IQR 13.3-47.3). Overall, radiologic complete thrombus resolution was observed in 64 (67%), partial resolution in 8 (9%), and no resolution in 23 (24%) infants. Complete resolution was significantly more frequent in infants with indwelling arterial catheter-related thrombosis compared with cardiac catheter-related thrombosis (P = .001). Patients with complete resolution had a significantly lower blood pressure difference and increased ankle-ankle index compared with patients with partial or no resolution (P < .0001). However, symptoms of claudication were present only in 1 case and clinical significant legs growth retardation (≥ 15 mm) was present in 1%. CONCLUSIONS: A significant percentage of persistent occlusion is present in children with arterial catheter-related thrombosis on long-term follow-up. In these children, the magnitude of leg growth retardation is small and possibly not clinically relevant. However, in children with congenital heart disease, the high prevalence of persistent arterial occlusion may hamper future diagnostic and/or interventional catheterization.

The Morbidity and Mortality Conference in Pediatric Intensive Care as a Means for Improving Patient Safety.

OBJECTIVES: To present our experience in an interdisciplinary and interprofessional morbidity and mortality conference, with special emphasis on its usefulness in improving patient safety. DESIGN: Retrospective analysis. SETTING: Tertiary interdisciplinary neonatal PICU. PATIENTS: Morbidity and mortality conference minutes on 48 patients (newborns to 17 yr), January 2009 to June 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors' PICU implemented a morbidity and mortality conference guideline in 2009 using a system-based approach to identify medical errors, their contributing factors, and possible solutions. In the subsequent 5.5 years, there were 44 mortality conferences (of 181 deaths [27%] over the same period) and four morbidity conferences. The median death/morbidity event-morbidity and mortality conference interval was 90 days (range, 7 d to 1.5 yr). The median age of patients was 4 months (range, newborn to 17 years). In six cases, the primary reason for PICU admission was a treatment complication. Unsafe processes/medical errors were identified and discussed in 37 morbidity and mortality conferences (77%). In seven cases, new autopsy findings prompted the discussion of a possible error. The 48 morbidity and mortality conferences identified 50 errors, including 30 in which an interface problem was a contributing factor. Fifty-four improvements were identified in 34 morbidity and mortality conferences. Four morbidity and mortality conferences discussed specific ethical issues. CONCLUSIONS: From our experience, we have found that the interdisciplinary and interprofessional morbidity and mortality conference has the potential to reveal unsafe processes/medical errors, in particular, diagnostic and communication errors and interface problems. When formatted as a nonhierarchical tool inviting contributions from all staff levels, the morbidity and mortality conference plays a key role in the system approach to medical errors.

Postoperative Hyperglycemia and 4-Year Neurodevelopmental Outcome in Children Operated for Congenital Heart Disease.

OBJECTIVES: To study the long-term neurodevelopmental effects of hyperglycemia in infant bypass surgery for congenital heart disease (CHD). STUDY DESIGN: Prospective cohort study on neurodevelopmental outcome after infant cardiac bypass surgery. EXCLUSION CRITERIA: age older than 1 year at first surgery, genetic comorbidity, and birth weight <2000 g. Of 167 eligible infants, follow-up examination at 4 years was completed in 150 children (90%). Intraoperative and postoperative highest and lowest glucose levels within 24 hours after bypass surgery were prospectively collected. Neurodevelopmental outcome at 4 years of age was assessed using standardized IQ tests and the Movement Assessment Battery for Children-second version for motor outcome assessment. RESULTS: Mean age at surgery was 2.8 months (0.1-10.7 months), 33% of children had an acyanotic CHD and 67% a cyanotic CHD. Glucose levels were elevated (>8 mmol/L) in 21 (14%) children in the first 24 postoperative hours. Glucose levels normalized in all children within 48 hours, 7 children (4%) received insulin infusions. Mean total IQ was within the normal range, but significantly lower than the normal population (92.5 [SD 15.0], P < .001). Higher postoperative glucose levels were related to better cognitive performance in the univariate analysis (P < .03), but not when other risk factors were taken into account. Independent risk factors for adverse outcome were lower socioeconomic status, higher risk adjustment for congenital heart surgery score, and longer duration of intensive care stay. CONCLUSION: Hyperglycemia is common in the early postoperative course after infant bypass surgery for CHD and normalizes within 48 hours. Hyperglycemia has no adverse effect on long-term neurodevelopmental outcome.

Subcutaneous fat necrosis in neonates with hypoxic ischaemic encephalopathy registered in the Swiss National Asphyxia and Cooling Register.

BACKGROUND: Neonates with hypoxic ischaemic encephalopathy (HIE) are routinely treated with therapeutic hypothermia (TH) for 72 h in order to improve neurological outcome. Subcutaneous fat necrosis (SCFN) is an adverse event occurring in neonates with HIE. METHODS: We analyzed risk factors for SCFN regarding demographic factors, cooling methods and deviation from target temperature range during hypothermia therapy. Data of all neonates registered in the National Asphyxia and Cooling Register in Switzerland between 2011 and 2013 were analyzed. RESULTS: 2.8% of all cooled neonates with HIE developed SCFN. Perinatal and neonatal characteristics did not differ between neonates with and without SCFN. Applied cooling methods did not correlate with the occurrence of SCFN. In neonates with SCFN 83.3% of all noted temperatures were within the target temperature range versus 77.5% in neonates without SCFN. Neonates with SCFN showed 3.6% of all measured temperatures below target temperature range compared to 12.7% in neonates without SCFN. CONCLUSION: Subcutaneous fat necrosis in the neonate with HIE undergoing TH is a potential adverse event that seems to occur independently from the whole-body cooling method applied and proportion of temperature measurements outside target temperature range. In this cohort, moderate overcooling associated with moderate hypothermia (33.0-34.0 °C) does not seem to be an independent risk factor for SCFN. There is no correlation between the severity of HIE and incidence of SCFN.

Does amplitude-integrated electroencephalogram background pattern correlate with cerebral injury in neonates with hypoxic-ischaemic encephalopathy?

AIMS: To determine the correlation between amplitude-integrated electroencephalogram (aEEG) background pattern and cerebral magnetic resonance imaging (MRI) in infants with hypoxic-ischaemic encephalopathy (HIE) and to examine whether the correlation changes with therapeutic hypothermia. METHODS: We included 38 term-born infants with HIE of whom 17 were cooled. All were continuously monitored with aEEG. Background pattern was scored at the beginning and the end of the recording. Cerebral MRI was obtained on median day 5 (2-11 days). Abnormalities were classified using a predefined scoring system for basal ganglia, watershed and overall injury, and then grouped into mild-moderate and severe. RESULTS: Abnormal aEEG background pattern correlated with more severe cerebral injury on MRI in the non-cooled infants (P < 0.01). In addition, cooled infants had less severe cerebral injury than non-cooled infants, in particular on T2-weighted images (watershed P = 0.04 and total injury score = 0.07). CONCLUSIONS: Abnormal aEEG background pattern is predictive of abnormal MRI, but therapeutic hypothermia seems to reduce this association. Thus, when cooling is applied in a clinical setting, the predictive value of aEEG may be limited.

Parents' Experiences of Therapeutic Hypothermia for Neonates With Hypoxic-Ischemic Encephalopathy (HIE): A Single-Center Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: The purpose of the study is to assess parental experiences of therapeutic hypothermia for moderate to severe hypoxic-ischemic encephalopathy with the goal of improving local clinical practice guidelines and fostering family-integrated care in neonates with hypoxic-ischemic encephalopathy. METHODS: This single-center retrospective cross-sectional study included neonates and their parents registered in the Swiss National Asphyxia and Cooling Register between 2011 and 2021. Based on a literature review, an anonymous survey of parents of neonates with hypoxic-ischemic encephalopathy was developed and conducted using an online survey tool. Descriptive statistics were used to analyze the survey results. RESULTS: The overall response rate to this survey was 64% (46/72). Sufficient information about hypoxic-ischemic encephalopathy was reported by 78% (36/46) of parents and sufficient information about the process of therapeutic hypothermia by 87% (40/46) of parents. The majority of parents indicated the need for, and at least a satisfactory perception of, professional (91%; 42/46) and emotional (87%; 40/46) support. Parents identified fostering family involvement and regular family communication that focuses on family integrated care as areas for improvement. CONCLUSIONS: There is still an unmet need for multidisciplinary teams to provide professional, empathetic, high quality, and family-integrated care to families with a neonate receiving therapeutic hypothermia for moderate or severe hypoxic-ischemic encephalopathy.

Blood Lactate Levels during Therapeutic Hypothermia and Neurodevelopmental Outcome or Death at 18-24 Months of Age in Neonates with Moderate and Severe Hypoxic-Ischemic Encephalopathy.

INTRODUCTION: Blood lactate levels in neonates with hypoxic-ischemic encephalopathy (HIE) vary, and their impact on neurodevelopmental outcome is unclear. We assessed blood lactate course over time in neonates with HIE during therapeutic hypothermia (TH) and investigated if blood lactate values were associated with neurodevelopmental outcome at 2 years of age. METHODS: This is a retrospective cohort study of neonates with HIE born between 2013 and 2019, treated at the University Children's Hospital Zurich. We recorded blood lactate values over time and calculated time until lactate was ≤2 mmol/L. Neurodevelopmental outcome was assessed at 18-24 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and categorized as favorable or unfavorable. We investigated associations between blood lactate values and outcome using logistic regression and adjusted for Sarnat stage. RESULTS: 33/45 neonates (69%) had a favorable and 14 (31%) an unfavorable neurodevelopmental outcome. Mean initial lactate values were lower in the favorable (13.9 mmol/L, standard deviation [SD]: 2.9) versus unfavorable group (17.1 mmol/L, SD 3.2; p = 0.002). Higher initial and maximal blood lactate levels were associated with unfavorable outcome, also when adjusted for Sarnat stage (adjusted odds ratio [aOR]: 1.37, 95% CI: 1.01-1.88, p = 0.046, and aOR: 1.35, 95% CI: 1.01-1.81, p = 0.041, respectively). CONCLUSION: In neonates with HIE receiving TH, initial and maximal blood lactate levels were associated with neurodevelopmental outcome at 18-24 months of age, also when adjusted for Sarnat stage. Further investigations to analyze blood lactate as a biomarker for prognostic value are needed.

Long-term neurodevelopmental outcome with hypoxic-ischemic encephalopathy.

OBJECTIVES: To determine the long-term neurodevelopmental outcome for children after hypoxic-ischemic encephalopathy (HIE) without major disability, and to examine neonatal injury patterns detected on cerebral magnetic resonance imaging (MRI) in relation to later deficits. STUDY DESIGN: Prospectively enrolled children with HIE and neonatal cerebral MRI data (n = 68) were examined at a mean age of 11.2 years (range, 8.2-15.7 years). Eleven children had a major disability (ie, cerebral palsy or mental retardation). Brain injury was scored according to the region and extent of injury. RESULTS: Children without major disability (n = 57) had lower full-scale and performance IQ scores compared with norms (P = .02 and .01, respectively), and the proportion of children with an IQ <85 was higher than expected (P = .04). Motor performance on the Zurich Neuromotor Assessment was affected in the pure motor, adaptive fine motor, and gross motor domains, as well as in the movement quality domain (all P < .001). Watershed injury pattern on neonatal MRI correlated with full-scale and verbal IQ scores (P = .006 and <.001, respectively), but neonatal MRI pattern did not correlate with motor performance in children without major disability. CONCLUSION: Children who sustained neonatal HIE without major disability are at increased risk for long-term intellectual, verbal, and motor deficits. The severity of watershed injury is correlated with later intellectual performance. Long-term follow-up examinations are necessary for early detection of neurodevelopmental impairment and early initiation of adequate therapies.

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.

Intermittent flushing improves cannula patency compared to continuous infusion for peripherally inserted venous catheters in newborns: results from a prospective observational study.

AIMS: Peripheral cannulas in newborns are commonly used for intravenous treatment. However sustained maintenance of cannula patency is often difficult to achieve in this age group. This study compares the duration for which cannula patency can be maintained in newborns under continuous infusion, or an intermittent flushing regimen, with normal saline. METHODS: A prospective observational study was conducted during a 12-month period. All newborns admitted to the 16-bed intermediate care unit, who required intravenous treatment, received either continuous peripheral infusion with 0.9% saline at an infusion rate of 2 mL/h or an intravenous cannula, which was flushed with 1 mL of 0.9% saline at least once every 24 h. RESULTS: A total of 53 patients with 86 cannulas were included. Twenty-five (47%) patients received 41 continuous infusions. The intermittent flushing group consisted of 28 (53%) patients with 45 cannulas administered. The cannula patency was significantly longer in the intermittent flushing group (mean 62.1 vs. 92.8 h, P=0.01). The patient's underlying disease and the cannula insertion site were not related with the duration of the cannula patency. CONCLUSIONS: Our study shows that intermittent cannula flushing is associated with improved cannula patency for peripherally inserted venous catheters in newborns.