Enteral plasma supports brain repair in newborn pigs after birth asphyxia.

Newborns exposed to birth asphyxia transiently experience deficient blood flow and a lack of oxygen, potentially inducing hypoxic-ischaemic encephalopathy and subsequent neurological damage. Immunomodulatory components in plasma may dampen these responses. Using caesarean-delivered pigs as a model, we hypothesized that dietary plasma supplementation improves brain outcomes in pigs exposed to birth asphyxia. Mild birth asphyxia was induced by temporary occlusion of the umbilical cord prior to caesarean delivery. Motor development was assessed in asphyxiated (ASP) and control (CON) piglets using neonatal arousal, physical activity and gait test parameters before euthanasia on Day 4. The ASP pigs exhibited increased plasma lactate at birth, deficient motor skills and increased glial fibrillary acidic protein levels in CSF and astrogliosis in the putamen. The expression of genes related to oxidative stress, inflammation and synaptic functions was transiently altered in the motor cortex and caudate nucleus. The number of apoptotic cells among CTIP2-positive neurons in the motor cortex and striatal medium spiny neurons was increased, and maturation of preoligodendrocytes in the internal capsule was delayed. Plasma supplementation improved gait performance in the beam test, attenuated neuronal apoptosis and affected gene expression related to neuroinflammation, neurotransmission and antioxidants (motor cortex, caudate). We present a new clinically relevant animal model of moderate birth asphyxia inducing structural and functional brain damage. The components in plasma that support brain repair remain to be identified but may represent a therapeutic potential for infants and animals after birth asphyxia.

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

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

Chest compressions superimposed with sustained inflations during cardiopulmonary resuscitation in asphyxiated pediatric piglets.

BACKGROUND: Pediatric resuscitation guidelines recommend continuous chest compression with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation. We recently described that providing a constant high distending pressure, or sustained inflation (SI) while performing continuous chest compressions (CC = CC + SI) reduces time to return of spontaneous circulation (ROSC) in neonatal and pediatric piglets with asphyxia-induced cardiac arrest. METHODS: To determine if CC + SI compared to CCaV will improve frequency of achieving ROSC and reduce time to ROSC in asphyxiated pediatric piglets. Twenty-eight pediatric piglets (21-24 days old) were anesthetized and asphyxiated by clamping the endotracheal tube. Piglets were randomized to CC + SI or CCaV for resuscitation (n = 14/group). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: The mean(SD) duration of resuscitation was significantly reduced with CC + SI compared to CCaV with 208(190) vs. 388(258)s, p = 0.045, respectively. The number of piglets achieving ROSC with CC + SI and CCaV were 12/14 vs. 6/14, p = 0.046. Minute ventilation, end-tidal carbon dioxide, ventilation rate, and positive end expiratory pressures were also significantly improved with CC + SI. CONCLUSIONS: CC + SI improves duration of resuscitation and increases number of piglets achieving ROSC secondary to improved minute ventilation. IMPACT: Chest compressions superimposed with sustained inflation resulted in shorter duration of resuscitation Chest compressions superimposed with sustained inflation resulted in higher number of piglets achieving return of spontaneous circulation Further animal studies are needed to examine chest compressions superimposed with sustained inflation.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Stakeholders' Perspectives on the "Helping Babies Breathe" Program Situation in Nepal Following the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic impacted healthcare systems, including resuscitation training programs such as Helping Babies Breathe (HBB). Nepal, a country with limited healthcare resources, faces challenges in delivering effective HBB training, managing deliveries, and providing neonatal care, particularly in remote areas. AIMS: This study assessed HBB skills and knowledge postpandemic through interviews with key stakeholders in Nepal. It aimed to identify strategies, adaptations, and innovations to address training gaps and scale-up HBB. METHODS: A qualitative approach was used, employing semistructured interviews about HBB program effectiveness, pandemic challenges, stakeholder engagement, and suggestions for improvement. RESULTS: The study encompassed interviews with 23 participants, including HBB trainers, birth attendants, officials, and providers. Thematic analysis employed a systematic approach by deducing themes from study aims and theory. Data underwent iterative coding and refinement to synthesize content yielding following 5 themes: (1) pandemic's impact on HBB training; (2) resource accessibility for training postpandemic; (3) reviving HBB training; (4) impacts on the neonatal workforce; and (5) elements influencing HBB training progress. CONCLUSION: Postpandemic, healthcare workers in Nepal encounter challenges accessing essential resources and delivering HBB training, especially in remote areas. Adequate budgeting and strong commitment from healthcare policy levels are essential to reduce neonatal mortality in the future.

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

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

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

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

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

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

Cardiopulmonary resuscitation in special circumstances.

Cardiopulmonary resuscitation prioritises treatment for cardiac arrests from a primary cardiac cause, which make up the majority of treated cardiac arrests. Early chest compressions and, when indicated, a defibrillation shock from a bystander give the best chance of survival with a good neurological status. Cardiac arrest can also be caused by special circumstances, such as asphyxia, trauma, pulmonary embolism, accidental hypothermia, anaphylaxis, or COVID-19, and during pregnancy or perioperatively. Cardiac arrests in these circumstances represent an increasing proportion of all treated cardiac arrests, often have a preventable cause, and require additional interventions to correct a reversible cause during resuscitation. The evidence for treating these conditions is mostly of low or very low certainty and further studies are needed. Irrespective of the cause, treatments for cardiac arrest are time sensitive and most effective when given early-every minute counts.

Assessing Neurovascular Coupling Using Wavelet Coherence in Neonates with Asphyxia.

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

Hypothermia cannot ameliorate renal fibrosis after asphyxia in the newborn piglet.

BACKGROUND: The effects of therapeutic hypothermia (TH) on renal function are not widely reported, especially in longer term animal models. The hypothesis of this study was that TH of the kidneys of hypoxic-ischemic newborn piglets would reduce pathological renal fibrosis. METHODS: Twenty-five newborn piglets obtained within 24 h of birth were classified into a control group (n = 5), an hypoxic insult with normothermia (HI-NT) group (n = 12), and an hypoxic insult with TH (HI-TH) group (33.5 °C ± 0.5 °C for 24 h; n = 8). Five days after the insult, all piglets were sacrificed under deep anesthesia by isoflurane inhalation. The kidneys were perfused with phosphate-buffered paraformaldehyde and immersed in formalin buffer. Territory fibrosis was studied and scored in the renal medulla using Azan staining. RESULTS: Fibrosis area scores (means ± standard deviations) based on Azan staining were 1.00 ± 0.46 in the control group, 2.85 ± 0.93 in the HI-NT group, and 3.58 ± 1.14 in the HI-TH group. The fibrosis area of the HI-NT and HI-TH groups was larger than that of the control. The HI-NT and HI-TH groups were not statistically different. CONCLUSIONS: Renal fibrosis is affected by perinatal asphyxia and cannot be prevented by TH, based on histopathological findings.

Human umbilical cord mesenchymal stromal cells as an adjunct therapy with therapeutic hypothermia in a piglet model of perinatal asphyxia.

BACKGROUND: With therapeutic hypothermia (HT) for neonatal encephalopathy, disability rates are reduced, but not all babies benefit. Pre-clinical rodent studies suggest mesenchymal stromal cells (MSCs) augment HT protection. AIMS: The authors studied the efficacy of intravenous (IV) or intranasal (IN) human umbilical cord-derived MSCs (huMSCs) as adjunct therapy to HT in a piglet model. METHODS: A total of 17 newborn piglets underwent transient cerebral hypoxia-ischemia (HI) and were then randomized to (i) HT at 33.5°C 1-13 h after HI (n = 7), (ii) HT+IV huMSCs (30 × 106 cells) at 24 h and 48 h after HI (n = 5) or (iii) HT+IN huMSCs (30 × 106 cells) at 24 h and 48 h after HI (n = 5). Phosphorus-31 and hydrogen-1 magnetic resonance spectroscopy (MRS) was performed at 30 h and 72 h and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells and oligodendrocytes quantified. In two further piglets, 30 × 106 IN PKH-labeled huMSCs were administered. RESULTS: HI severity was similar between groups. Amplitude-integrated electroencephalogram (aEEG) recovery was more rapid for HT+IN huMSCs compared with HT from 25 h to 42 h and 49 h to 54 h (P ≤ 0.05). MRS phosphocreatine/inorganic phosphate was higher on day 2 in HT+IN huMSCs than HT (P = 0.035). Comparing HT+IN huMSCs with HT and HT+IV huMSCs, there were increased OLIG2 counts in hippocampus (P = 0.011 and 0.018, respectively), internal capsule (P = 0.013 and 0.037, respectively) and periventricular white matter (P = 0.15 for IN versus IV huMSCs). Reduced TUNEL-positive cells were seen in internal capsule with HT+IN huMSCs versus HT (P = 0.05). PKH-labeled huMSCs were detected in the brain 12 h after IN administration. CONCLUSIONS: After global HI, compared with HT alone, the authors saw beneficial effects of HT+IN huMSCs administered at 24 h and 48 h (30 × 106 cells/kg total dose) based on more rapid aEEG recovery, improved 31P MRS brain energy metabolism and increased oligodendrocyte survival at 72 h.

Continuous chest compressions with asynchronous ventilation improve survival in a neonatal swine model of asphyxial cardiac arrest.

BACKGROUND: Guidelines for neonatal resuscitation recommend a 3:1 compression to ventilation ratio. However, this recommendation is based on expert opinion and consensus rather than strong scientific evidence. Our primary aim was to assess whether continuous chest compressions with asynchronous ventilations would increase return of spontaneous circulation (ROSC) rate and survival compared to the 3:1 chest compression to ventilation ratio. METHODS: This was a prospective, randomized, laboratory study. Twenty male Landrace-Large White pigs, aged 1-4 days with an average weight 1.650 ± 228.3 g were asphyxiated and left untreated until heart rate was less than 60 bpm or mean arterial pressure was below 15 mmHg. Animals were then randomly assigned to receive either continuous chest compressions with asynchronous ventilations (n = 10), or standard (3:1) chest compression to ventilation ratio (n = 10). Heart rate and arterial pressure were assessed every 30 s during cardiopulmonary resuscitation (CPR) until ROSC or asystole. All animals with ROSC were monitored for 4 h. RESULTS: Coronary perfusion pressure (CPP) at 30 s of CPR was significantly higher in the experimental group (45.7 ± 16.9 vs. 21.8 ± 6 mmHg, p < 0.001) and remained significantly elevated throughout the experiment. End-tidal carbon dioxide (ETCO2) was also significantly higher in the experimental group throughout the experiment (23.4 ± 5.6 vs. 14.7 ± 5.9 mmHg, p < 0.001). ROSC was observed in six (60%) animals treated with 3:1 compression to ventilation ratio and nine (90%) animals treated with continuous chest compressions and asynchronous ventilation (p = 0.30). Time to ROSC was significantly lower in the experimental group (30 (30-30) vs. 60 (60-60) sec, p = 0.021). Of note, 7 (77.8%) animals in the experimental group and 1 (16.7%) animal in the control group achieved ROSC after 30 s (0.02). At 4 h, 2 (20%) animals survived in the control group compared to 7 (70%) animals in the experimental group (p = 0.022). CONCLUSION: Continuous chest compressions with asynchronous ventilations significantly improved CPP, ETCO2, time to ROSC, ROSC at 30 s and survival in a porcine model of neonatal resuscitation.

Practical oxygen therapy for newborn piglets.

Aims: To evaluate the effect of a novel method of practical oxygen therapy on physiological parameters related to survival, weaning weight and preweaning mortality of neonatal piglets under commercial farm conditions. Methods: Piglets from hyperprolific sows born with signs of asphyxia, (n = 109; <6 on a score of respiration, meconium staining and activity) or very low birth weight (VLBW; n = 112; <1.05 kg) were selected for the study. Approximately half of each group (n = 55 VLBW piglets and n = 57 piglets with asphyxia) received 100% oxygen immediately after birth using a specially designed facemask for 45 seconds (VLBW) or 1 minute (asphyxiated). Physiological parameters (peripheral blood oxygen saturation (SpO2) blood glucose concentration and rectal temperature) were measured before oxygen treatment 5 minutes after birth (SpO2) and 24 hours later (SpO2, blood glucose concentration, temperature). Weight at birth, at 24 hours and at 21 days of age, preweaning mortality, and estimated colostrum intake were also recorded. Results: A significant treatment effect on SpO2 was observed (p = 0.013 and p < 0.001 for VLBW and asphyxiated piglets respectively). VLBW and asphyxiated piglets that received oxygen treatment had higher SpO2 after treatment (measured 5 minutes after birth, 97.7 and 97.8% respectively) compared to immediately after birth (93.3 and 86.8% respectively) while untreated piglets showed no variation. Blood glucose concentrations increased in all piglets between birth and 24 hours of age (p = 0.003 and p < 0.001 for asphyxiated and VLBW piglets respectively) and this was higher in asphyxiated piglets that received oxygen than those that did not (5.6 (SE 0.2) mmol/L; p < 0.05). Estimated colostrum intake was higher in asphyxiated (401.6 (SD 24.4) g/kg) and VLBW (374.9 (SE 23.4 g/kg) piglets that received oxygen than those that did not (273.2 (SE 24.1) g/kg; p < 0.001 and 249.0 (SE 22.5) g/kg; p < 0.001 respectively). Similarly weight at weaning was higher in asphyxiated (5.8 (SE 0.2) kg) and VLBW (4.9 (SE 0.2) kg) piglets that received oxygen therapy than control animals (4.9 (SE 0.2) kg; = 0.005 and 4.1 (SE 0.2) kg; p = 0.008 respectively). Furthermore, oxygen treatment markedly reduced preweaning mortality from 9/52 (17%) untreated to 1/57 (1.7%) oxygen-treated piglets suffering asphyxia at birth (p = 0.006). Conclusions: Oxygen therapy improves physiological and productive parameters in piglets born with signs of asphyxia or VLBW. The incorporation of this strategy as part of the farrowing routine enhances the advantages of rearing hyperprolific sows.

The Effect of Asphyxia Arrest Duration on a Pediatric End-Tidal CO2-Guided Chest Compression Delivery Model.

OBJECTIVES: To determine the effect of the duration of asphyxial arrest on the survival benefit previously seen with end-tidal CO2-guided chest compression delivery. DESIGN: Preclinical randomized controlled study. SETTING: University animal research laboratory. SUBJECTS: Two-week-old swine. INTERVENTIONS: After either 17 or 23 minutes of asphyxial arrest, animals were randomized to standard cardiopulmonary resuscitation or end-tidal CO2-guided chest compression delivery. Standard cardiopulmonary resuscitation was optimized by marker, monitor, and verbal feedback about compression rate, depth, and release. End-tidal CO2-guided delivery used adjustments to chest compression rate and depth to maximize end-tidal CO2 level without other feedback. Cardiopulmonary resuscitation for both groups proceeded from 10 minutes of basic life support to 10 minutes of advanced life support or return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: After 17 minutes of asphyxial arrest, mean end-tidal CO2 during 10 minutes of cardiopulmonary resuscitation was 18 ± 9 torr in the standard group and 33 ± 15 torr in the end-tidal CO2 group (p = 0.004). The rate of return of spontaneous circulation was three of 14 (21%) in the standard group rate and nine of 14 (64%) in the end-tidal CO2 group (p = 0.05). After a 23-minute asphyxial arrest, neither end-tidal CO2 values (20 vs 26) nor return of spontaneous circulation rate (3/14 vs 1/14) differed between the standard and end-tidal CO2-guided groups. CONCLUSIONS: Our previously observed survival benefit of end-tidal CO2-guided chest compression delivery after 20 minutes of asphyxial arrest was confirmed after 17 minutes of asphyxial arrest. The poor survival after 23 minutes of asphyxia shows that the benefit of end-tidal CO2-guided chest compression delivery is limited by severe asphyxia duration.

Hanging and near hanging in children: injury patterns and a clinical approach to early management.

Near hanging refers to survival following suspension by the neck. This is a devastating injury which can lead to mortality or serious long-term morbidity. Children and young people present to emergency departments following accidental or deliberate near hanging. This article describes the patterns of injury, the initial management and important prognostic factors.

Reducing mortality in near-hanging patients with a novel early management protocol.

BACKGROUND: Hanging is one of the most common causes of suicide world-wide, more prevalent in developing countries. There are no established protocols for early management of near-hanging patients who present to the emergency department (ED). The use of early intubation, strict blood pressure control and targeted temperature management has shown promise in small studies. OBJECTIVE: To detect changes in mortality and neurological deficits in near-hanging patients before and after implementation of a novel early management protocol in a tertiary care hospital in India. METHODS: Prospective cohort study conducted at a tertiary-care hospital in Tamil Nadu, India from August 2014-July 2016. For first year of study (pre-implementation), near-hanging patients were treated without a structured protocol. For second year of study (post-implementation), near-hanging patients were treated per a protocol including early intubation, strict blood pressure control and targeted temperature management. Primary outcomes included: (1) in-hospital mortality and (2) hospital discharge without neurological deficit. RESULTS: 65 patients were included (27 in the pre-implementation phase and 38 in the post-implementation phase.) At presentation, there was no difference between the two groups in mean heart rate, mean arterial pressure, mean oxygen saturation, Glasgow coma score, or mean respiratory rate. Protocol implementation decreased mortality (10/27 (37%) versus 2/38 (5%), P < 0.05) and increased the number of patients discharged without neurological deficit (10/27 (37%) versus 35/38 (92%), P < 0.05). CONCLUSIONS: This novel early management protocol reduced mortality and increased the number discharged without neurological deficit in near-hanging patients in a single tertiary care center in India.

Amikacin Pharmacokinetics To Optimize Dosing in Neonates with Perinatal Asphyxia Treated with Hypothermia.

Aminoglycoside pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed for treating neonates with (suspected) septicemia; however, none provide adjustments for cases of PATH. Therefore, we aimed to quantify the differences in amikacin PK between neonates with and without PATH to propose suitable dosing recommendations. Based on amikacin therapeutic drug monitoring data collected retrospectively from neonates with PATH, combined with a published data set, we assessed the impact of PATH on amikacin PK by using population modeling. Monte Carlo and stochastic simulations were performed to establish amikacin exposures in neonates with PATH after dosing according to the current guidelines and according to proposed model-derived dosing guidelines. Amikacin clearance was decreased 40.6% in neonates with PATH, with no changes in volume of distribution. Simulations showed that increasing the dosing interval by 12 h results in a decrease in the percentage of neonates reaching toxic trough levels (>5 mg/liter), from 40 to 76% to 14 to 25%, while still reaching efficacy targets compared to the results of current dosing regimens. Based on this study, a 12-h increase in the amikacin dosing interval in neonates with PATH is proposed to correct for the reduced clearance, yielding safe and effective exposures. As amikacin is renally excreted, further studies into other renally excreted drugs may be required, as their clearance may also be impaired.

Enduring disturbances in regional cerebral blood flow and brain oxygenation at 24 h after asphyxial cardiac arrest in developing rats.

BACKGROUND: Disturbances in cerebral blood flow (CBF) and brain oxygenation (PbO2) are present early after pediatric cardiac arrest (CA). CBF-targeted therapies improved neurological outcome in our CA model. To assess the therapeutic window for CBF- and PbO2-targeted therapies, we propose to determine if CBF and PbO2 disturbances persist at 24 h after experimental pediatric CA. METHODS: Regional CBF and PbO2 were measured at 24 h after asphyxial CA in immature rats (n = 26, 6-8/group) using arterial spin label MRI and tissue electrodes, respectively. RESULTS: In all regions but the thalamus, CBF recovered to sham values by 24 h; thalamic CBF was >32% higher after CA vs. sham. PbO2 values at 24 h after CA in the cortex and thalamus were similar to shams in rats who received supplemental oxygen, however, on room air, cortical PbO2 was lower after CA vs. shams. CONCLUSION: CBF remains increased in the thalamus at 24 h after CA and PbO2 is decreased to hypoxic levels in cortex at 24 h after CA in rats who do not receive supplemental oxygen. Given the enduring disturbances in this model and the lack of routine CBF or PbO2 monitoring in patients, our data suggest the need for clinical correlation.

Continuous Chest Compressions During Sustained Inflations in a Perinatal Asphyxial Cardiac Arrest Lamb Model.

OBJECTIVE: Continuous chest compressions are more effective during resuscitation in adults. Sustained inflation rapidly establishes functional residual capacity in fluid-filled lungs at birth. We sought to compare the hemodynamics and success in achieving return of spontaneous circulation in an asphyxial cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs between subjects receiving continuous chest compressions during sustained inflation and those receiving conventional 3:1 compression-to-ventilation resuscitation. DESIGN: Prospective, randomized, animal model study. SETTING: An experimental laboratory. SUBJECTS: Fourteen newborn term gestation lambs. INTERVENTIONS: Lambs were randomized into two groups: 3:1 compression-to-ventilation (control) and continuous chest compressions during sustained inflation. The umbilical cord was occluded to induce asphyxia and asystole. The control group was resuscitated per NRP guidelines. In the sustained inflation + continuous chest compressions group, sustained inflation at 35 cm H2O was provided for 30 seconds with 1-second interruptions before another sustained inflation was provided. One hundred twenty chest compressions/min started after the initial sustained inflation. The first dose of IV epinephrine was given at 6 minutes if return of spontaneous circulation was not achieved and then every 3 minutes until return of spontaneous circulation or for a total of four doses. MEASUREMENT AND RESULTS: All lambs achieved return of spontaneous circulation in a comparable median time (interquartile range) of 390 seconds (225-405 s) and 345 seconds (204-465 s) in the sustained inflation + continuous chest compressions and control groups, respectively. Four of seven (sustained inflation + continuous chest compressions) and three of six (control) lambs required epinephrine to achieve return of spontaneous circulation. Diastolic blood pressures were lower in the sustained inflation + continuous chest compressions (4 ± 2 mm Hg) compared to the control group (7 ± 2 mm Hg), p < 0.05. PaCO2, PaO2, and lactate were similar between the groups during the study period. CONCLUSION: In this perinatal cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs, sustained inflation + continuous chest compressions is as effective as 3:1 compression-to-ventilation resuscitation in achieving return of spontaneous circulation. Half the lambs achieved return of spontaneous circulation without epinephrine. continuous chest compressions during sustained inflation reduced diastolic pressures but did not alter gas exchange or carotid blood flow compared to 3:1 compression-to-ventilation resuscitation.