ABSTRACT
OBJECTIVE: To determine the causal relationship between exposure to early hyperoxemia and death or major disability in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We analyzed data from the Infant Cooling Evaluation (ICE) trial that enrolled newborns ≥35 weeks' gestation with moderate-severe HIE, randomly allocated to hypothermia or normothermia. The primary outcome was death or major sensorineural disability at 2 years. We included infants with arterial pO2 measured within 2 hours of birth. Using a directed acyclic graph, we established that markers of severity of perinatal hypoxia-ischemia and pCO2 were a minimally sufficient set of variables for adjustment in a regression model to estimate the causal relationship between arterial pO2 and death/disability. RESULTS: Among 221 infants, 116 (56%) had arterial pO2 and primary outcome data. The unadjusted analysis revealed a U-shaped relationship between arterial pO2 and death or major disability. Among hyperoxemic infants (pO2 100-500 mmHg) the proportion with death or major disability was 40/58 (0.69), while the proportion in normoxemic infants (pO2 40-99 mmHg) was 20/48 (0.42). In the adjusted model, hyperoxemia increased the risk of death or major disability (adjusted risk ratio 1.61, 95% CI 1.07-2.00, P = .03) in relation to normoxemia. CONCLUSION: Early hyperoxemia increased the risk of death or major disability among infants who had an early arterial pO2 in the ICE trial. Limitations include the possibility of residual confounding and other causal biases. Further work is warranted to confirm this relationship in the era of routine therapeutic hypothermia.
Subject(s)
Hypothermia, Induced , Hypoxia-Ischemia, Brain , Infant , Pregnancy , Female , Infant, Newborn , Humans , Hypoxia-Ischemia, Brain/therapy , Hypoxia-Ischemia, Brain/complications , Hypoxia/therapy , Cold Temperature , Hypothermia, Induced/adverse effects , Gestational AgeABSTRACT
BACKGROUND: Cord-clamping strategies may modify blood pressure (BP) and cerebral tissue oxygen saturation (rStO2) immediately after birth. METHODS: We conducted a sub-study nested within the Baby-Directed Umbilical Cord-Clamping trial. Infants ≥32+0 weeks' gestation assessed as requiring resuscitation were randomly allocated to either physiologically-based cord clamping (PBCC), where resuscitation commenced prior to umbilical cord clamping, or standard care where cord clamping occurred early (ECC). In this single-site sub-study, we obtained additional measurements of pre-ductal BP and rStO2. In a separate observational arm, non-randomised vigorous infants received 2 min of deferred cord clamping (DCC) and contributed data for reference percentiles. RESULTS: Among 161 included infants, n = 55 were randomly allocated to PBCC (n = 30) or ECC (n = 25). The mean (SD) BP at 3-4 min after birth (primary outcome) in the PBCC group was 64 (10) mmHg compared to 62 (10) mmHg in the ECC group, mean difference 2 mmHg (95% confidence interval -3-8 mmHg, p = 0.42). BP and rStO2 were similar across both randomised arms and the observational arm (n = 106). CONCLUSION: We found no difference in BP or rStO2 with the different cord clamping strategies. We report reference ranges for BP and rStO2 for late-preterm and full-term infants receiving DCC. IMPACT: Among late-preterm and full-term infants receiving varying levels of resuscitation, blood pressure (BP, at 3-4 minutes and 6 min) and cerebral tissue oxygen saturation (rStO2) are not influenced by timing of cord clamping in relation to establishment of ventilation. Infants in this study did not require advanced resuscitation, where cord clamping strategies may yet influence BP and rStO2. The reference ranges for BP and rStO2 represent the first, to our knowledge, for vigorous late-preterm and full-term infants receiving deferred cord clamping. rStO2 > 90% (~90th percentile) may be used to define cerebral hyperoxia, for instance when studying oxygen supplementation after birth.
Subject(s)
Blood Pressure , Umbilical Cord Clamping , Humans , Infant, Newborn , Female , Male , Oxygen/metabolism , Oxygen/blood , Umbilical Cord , Brain/metabolism , Oxygen Saturation , Resuscitation/methodsABSTRACT
To identify characteristics associated with delivery room clinical instability in at-risk infants. Prospective cohort study. Two perinatal centres in Melbourne, Australia. Infants born at ≥ 35+0 weeks' gestation with a first-line paediatric doctor requested to attend. Clinical instability defined as any one of heart rate < 100 beats per minute for ≥ 20 s in the first 10 min after birth, maximum fraction of inspired oxygen of ≥ 0.70 in the first 10 min after birth, 5-min Apgar score of < 7, intubated in the delivery room or admitted to the neonatal unit for respiratory support. Four hundred and seventy-three infants were included. The median (IQR) gestational age at birth was 39+4 (38+4-40+4) weeks. Eighty (17%) infants met the criteria for clinical instability. Independent risk factors for clinical instability were labour without oxytocin administration, presence of a medical pregnancy complication, difficult extraction at birth and unplanned caesarean section in labour. Decision tree analysis determined that infants at highest risk were those whose mothers did not receive oxytocin during labour (25% risk). Infants at lowest risk were those whose mothers received oxytocin during labour and did not have a medical pregnancy complication (7% risk). CONCLUSIONS: We identified characteristics associated with clinical instability that may be useful in alerting less experienced clinicians to call for senior assistance early. The decision trees provide intuitive visual aids but require prospective validation. WHAT IS KNOWN: ⢠First-line clinicians attending at-risk births may need to call senior colleagues for assistance depending on the infant's condition. ⢠Delays in effectively supporting a compromised infant at birth is an important cause of neonatal morbidity and infant-mother separation. WHAT IS NEW: ⢠This study identifies risk factors for delivery room clinical instability in at-risk infants born at ≥ 35+0 weeks' gestation. ⢠The decision trees presented provide intuitive visual tools to aid in determining the need for senior paediatric presence.
Subject(s)
Cesarean Section , Pregnancy Complications , Infant, Newborn , Infant , Pregnancy , Humans , Female , Child , Oxytocin , Prospective Studies , Gestational AgeABSTRACT
BACKGROUND: Globally, the majority of newborns requiring resuscitation at birth are full term or late-preterm infants. These infants typically have their umbilical cord clamped early (ECC) before moving to a resuscitation platform, losing the potential support of the placental circulation. Physiologically based cord clamping (PBCC) is clamping the umbilical cord after establishing lung aeration and holds promise as a readily available means of improving early newborn outcomes. In mechanically ventilated lambs, PBCC improved cardiovascular stability and reduced hypoxia. We hypothesised that PBCC compared to ECC would result in higher heart rate (HR) in infants needing resuscitation, without compromising safety. METHODS AND FINDINGS: Between 4 July 2018 and 18 May 2021, infants born at ≥32+0 weeks' gestation with a paediatrician called to attend were enrolled in a parallel-arm randomised trial at 2 Australian perinatal centres. Following initial stimulation, infants requiring further resuscitation were randomised within 60 seconds of birth using a smartphone-accessible web link. The intervention (PBCC) was to establish lung aeration, either via positive pressure ventilation (PPV) or effective spontaneous breathing, prior to cord clamping. The comparator was early cord clamping (ECC) prior to resuscitation. The primary outcome was mean HR between 60 to 120 seconds after birth, measured using 3-lead electrocardiogram, extracted from video recordings blinded to group allocation. Nonrandomised infants had deferred cord clamping (DCC) ≥120 seconds in the observational study arm. Among 508 at-risk infants enrolled, 123 were randomised (n = 63 to PBCC, n = 60 to ECC). Median (interquartile range, IQR) for gestational age was 39.9 (38.3 to 40.7) weeks in PBCC infants and 39.6 (38.4 to 40.4) weeks in ECC infants. Approximately 49% and 50% of the PBCC and ECC infants were female, respectively. Five infants (PBCC = 2, ECC = 3, 4% total) had missing primary outcome data. Cord clamping occurred at a median (IQR) of 136 (126 to 150) seconds in the PBCC arm and 37 (27 to 51) seconds in the ECC arm. Mean HR between 60 to 120 seconds after birth was 154 bpm (beats per minute) for PBCC versus 158 bpm for ECC (adjusted mean difference -6 bpm, 95% confidence interval (CI) -17 to 5 bpm, P = 0.39). Among 31 secondary outcomes, postpartum haemorrhage ≥500 ml occurred in 34% and 32% of mothers in the PBCC and ECC arms, respectively. Two hundred ninety-five nonrandomised infants (55% female) with median (IQR) gestational age of 39.6 (38.6 to 40.6) weeks received DCC. Data from these infants was used to create percentile charts of expected HR and oxygen saturation in vigorous infants receiving DCC. The trial was limited by the small number of infants requiring prolonged or advanced resuscitation. PBCC may provide other important benefits we did not measure, including improved maternal-infant bonding and higher iron stores. CONCLUSIONS: In this study, we observed that PBCC resulted in similar mean HR compared to infants receiving ECC. The findings suggest that for infants ≥32+0 weeks' gestation who receive brief, effective resuscitation at closely monitored births, PBCC does not provide additional benefit over ECC (performed after initial drying and stimulation) in terms of key physiological markers of transition. PBCC was feasible using a simple, low-cost strategy at both cesarean and vaginal births. The percentile charts of HR and oxygen saturation may guide clinicians monitoring the transition of at-risk infants who receive DCC. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000621213.
Subject(s)
Infant, Premature , Oxygen Saturation , Animals , Australia , Constriction , Female , Gestational Age , Heart Rate , Humans , Infant, Newborn , Male , Parturition , Placenta , Pregnancy , Sheep , Time FactorsABSTRACT
Blood oxygen in the fetus is substantially lower than in the newborn infant. In the minutes after birth, arterial oxygen saturation rises from around 50-60% to 90-95%. Initial respiratory efforts generate negative trans-thoracic pressures that drive liquid from the airways into the lung interstitium facilitating lung aeration, blood oxygenation, and pulmonary artery vasodilatation. Consequently, intra- (foramen ovale) and extra-cardiac (ductus arteriosus) shunting changes and the sequential circulation switches to a parallel pulmonary and systemic circulation. Delaying cord clamping preserves blood flow through the ascending vena cava, thus increasing right and left ventricular preload. Recently published reference ranges have suggested that delayed cord clamping positively influenced the fetal-to-neonatal transition. Oxygen saturation in babies with delayed cord clamping plateaus significantly earlier to values of 85-90% than in babies with immediate cord clamping. Delayed cord clamping may also contribute to fewer episodes of brady-or-tachycardia in the first minutes after birth, but data from randomized trials are awaited. IMPACT: Delaying cord clamping during fetal to neonatal transition contributes to a significantly earlier plateauing of oxygen saturation and fewer episodes of brady-and/or-tachycardia in the first minutes after birth. We provide updated information regarding the changes in SpO2 and HR during postnatal adaptation of term and late preterm infants receiving delayed compared with immediate cord clamping. Nomograms in newborn infants with delayed cord clamping will provide valuable reference ranges to establish target SpO2 and HR in the first minutes after birth.
ABSTRACT
Randomised trials in emergency settings must quickly confirm eligibility and allocate participants to an intervention group without delaying treatment. We report rapid randomisation during two neonatal resuscitation trials using the non-commercial REDCap platform accessed via smartphone. This simple, reliable method has wide applicability for trials in emergency settings. What is Known: ⢠Randomised trials in emergency settings need to rapidly allocate participants to an intervention group. ⢠This process should not delay treatment. What is New: ⢠This non-commercial, smartphone-accessible application enabled rapid, accurate randomisation at the bedside. ⢠This has broad applicability for emergency setting trials.
Subject(s)
Resuscitation , Smartphone , Humans , Infant, Newborn , Research DesignABSTRACT
Preterm newborns are highly susceptible to bacterial infections. This susceptibility is regarded as being due to immaturity of multiple pathways of the immune system. However, it is unclear whether a mechanism that unifies these different, suppressed pathways exists. Here, we argue that the immune vulnerability of the preterm neonate is critically related to arginine depletion. Arginine, a "conditionally essential" amino acid, is depleted in acute catabolic states, including sepsis. Its metabolism is highly compartmentalized and regulated, including by arginase-mediated hydrolysis. Recent data suggest that arginase II-mediated arginine depletion is essential for the innate immune suppression that occurs in newborn models of bacterial challenge, impairing pathways critical for the immune response. Evidence that arginine depletion mediates protection from immune activation during first gut colonization suggests a regulatory role in controlling gut-derived pathogens. Clinical studies show that plasma arginine is depleted during sepsis. In keeping with animal studies, small clinical trials of L-arginine supplementation have shown benefit in reducing necrotizing enterocolitis in premature neonates. We propose a novel, broader hypothesis that arginine depletion during bacterial challenge is a key factor limiting the neonate's ability to mount an adequate immune response, contributing to the increased susceptibility to infections, particularly with respect to gut-derived sepsis.
Subject(s)
Arginine/deficiency , Bacterial Infections/etiology , Disease Susceptibility/immunology , Immunity, Innate/immunology , Infant, Premature/immunology , Microbiota/immunology , Models, Immunological , Arginine/immunology , Arginine/metabolism , Bacterial Infections/immunology , Gastrointestinal Tract/microbiology , Humans , Infant, Newborn , Signal Transduction/immunologyABSTRACT
INTRODUCTION: Endotracheal (ET) epinephrine administration is an option during neonatal resuscitation, if the preferred intravenous (IV) route is unavailable. OBJECTIVES: We assessed whether endotracheal epinephrine achieved return of spontaneous circulation (ROSC), and maintained physiological stability after ROSC, at standard and higher dose, in severely asphyxiated newborn lambs. METHODS: Near-term fetal lambs were asphyxiated until asystole. Resuscitation was commenced with ventilation and chest compressions. Lambs were randomly allocated to: IV Saline placebo (5 ml/kg), IV Epinephrine (20 micrograms/kg), Standard-dose ET Epinephrine (100 micrograms/kg), and High-dose ET Epinephrine (1 mg/kg). After three allocated treatment doses, rescue IV Epinephrine was administered if ROSC had not occurred. Lambs achieving ROSC were monitored for 60 minutes. Brain histology was assessed for microbleeds. RESULTS: ROSC in response to allocated treatment (without rescue IV Epinephrine) occurred in 1/6 Saline, 9/9 IV Epinephrine, 0/9 Standard-dose ET Epinephrine, and 7/9 High-dose ET Epinephrine lambs respectively. Blood pressure during CPR increased after treatment with IV Epinephrine and High-dose ET Epinephrine, but not Saline or Standard-dose ET Epinephrine. After ROSC, both ET Epinephrine groups had lower pH, higher lactate, and higher blood pressure than the IV Epinephrine group. Cortex microbleeds were more frequent in High-dose ET Epinephrine lambs (8/8 lambs examined, versus 3/8 in IV Epinephrine lambs). CONCLUSIONS: The currently recommended dose of ET Epinephrine was ineffective in achieving ROSC. Without convincing clinical or preclinical evidence of efficacy, use of ET Epinephrine at this dose may not be appropriate. High-dose ET Epinephrine requires further evaluation before clinical translation.
Subject(s)
Animals, Newborn , Cardiopulmonary Resuscitation , Epinephrine , Heart Arrest , Animals , Epinephrine/administration & dosage , Sheep , Cardiopulmonary Resuscitation/methods , Heart Arrest/therapy , Heart Arrest/drug therapy , Vasoconstrictor Agents/administration & dosage , Dose-Response Relationship, Drug , Intubation, Intratracheal/methods , Disease Models, Animal , Return of Spontaneous Circulation/drug effects , Random AllocationABSTRACT
OBJECTIVE: During neonatal resuscitation, the return of spontaneous circulation (ROSC) can be achieved using epinephrine which optimises coronary perfusion by increasing diastolic pressure. Abdominal compression (AC) applied during resuscitation could potentially increase diastolic pressure and therefore help achieve ROSC. We assessed the use of AC during resuscitation of asystolic newborn lambs, with and without epinephrine. METHODS: Near-term fetal lambs were instrumented for physiological monitoring and after delivery, asphyxiated until asystole. Resuscitation was commenced with ventilation followed by chest compressions. Lambs were randomly allocated to: intravenous epinephrine (20 µg/kg, n=9), intravenous epinephrine+continuous AC (n=8), intravenous saline placebo (5 mL/kg, n=6) and intravenous saline+AC (n=9). After three allocated treatment doses, rescue intravenous epinephrine was administered if ROSC had not occurred. Time to achieve ROSC was the primary outcome. Lambs achieving ROSC were ventilated and monitored for 60 min before euthanasia. Brain histology was assessed for micro-haemorrhage. RESULTS: Use of AC did not influence mean time to achieve ROSC (epinephrine lambs 177 s vs epinephrine+AC lambs 179 s, saline lambs 602 s vs saline+AC lambs 585 s) or rate of ROSC (nine of nine lambs, eight of eight lambs, one of six lambs and two of eight lambs, respectively). Application of AC was associated with higher diastolic blood pressure (mean value >10 mm Hg), mean and systolic blood pressure and carotid blood flow during resuscitation. Cortex and deep grey matter micro-haemorrhage was more frequent in AC lambs. CONCLUSION: Use of AC during resuscitation increased diastolic blood pressure, but did not impact time to ROSC.
Subject(s)
Animals, Newborn , Epinephrine , Animals , Epinephrine/administration & dosage , Sheep , Heart Arrest/therapy , Cardiopulmonary Resuscitation/methods , Return of Spontaneous Circulation , Resuscitation/methods , Random Allocation , Asphyxia Neonatorum/therapy , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/therapeutic use , Disease Models, AnimalABSTRACT
BACKGROUND: The increasing frequency and intensity of dengue outbreaks in endemic and non-endemic countries requires a rational, evidence based response. To this end, we aimed to collate the experiences of a number of affected countries, identify strengths and limitations in dengue surveillance, outbreak preparedness, detection and response and contribute towards the development of a model contingency plan adaptable to country needs. METHODS: The study was undertaken in five Latin American (Brazil, Colombia, Dominican Republic, Mexico, Peru) and five in Asian countries (Indonesia, Malaysia, Maldives, Sri Lanka, Vietnam). A mixed-methods approach was used which included document analysis, key informant interviews, focus-group discussions, secondary data analysis and consensus building by an international dengue expert meeting organised by the World Health Organization, Special Program for Research and Training in Tropical Diseases (WHO-TDR). RESULTS: Country information on dengue is based on compulsory notification and reporting ("passive surveillance"), with laboratory confirmation (in all participating Latin American countries and some Asian countries) or by using a clinical syndromic definition. Seven countries additionally had sentinel sites with active dengue reporting, some also had virological surveillance. Six had agreed a formal definition of a dengue outbreak separate to seasonal variation in case numbers. Countries collected data on a range of warning signs that may identify outbreaks early, but none had developed a systematic approach to identifying and responding to the early stages of an outbreak. Outbreak response plans varied in quality, particularly regarding the early response. The surge capacity of hospitals with recent dengue outbreaks varied; those that could mobilise additional staff, beds, laboratory support and resources coped best in comparison to those improvising a coping strategy during the outbreak. Hospital outbreak management plans were present in 9/22 participating hospitals in Latin-America and 8/20 participating hospitals in Asia. CONCLUSIONS: Considerable variation between countries was observed with regard to surveillance, outbreak detection, and response. Through discussion at the expert meeting, suggestions were made for the development of a more standardised approach in the form of a model contingency plan, with agreed outbreak definitions and country-specific risk assessment schemes to initiate early response activities according to the outbreak phase. This would also allow greater cross-country sharing of ideas.
Subject(s)
Dengue/epidemiology , Disease Outbreaks , Asia/epidemiology , Evidence-Based Medicine , Humans , Latin America/epidemiology , Models, Statistical , Population Surveillance/methods , Risk AssessmentABSTRACT
INTRODUCTION: Recent reports have raised concerns of cardiorespiratory deterioration in some infants receiving respiratory support at birth. We aimed to independently determine whether respiratory support with a facemask is associated with a decrease in heart rate (HR) in some late-preterm and term infants. METHODS: Secondary analysis of data from infants born at ≥32+0 weeks of gestation at 2 perinatal centres in Melbourne, Australia. Change in HR up to 120 s after facemask placement, measured using 3-lead electrocardiography, was assessed every 3 s until 60 s and every 5 s thereafter from video recordings. RESULTS: In the 15 s after facemask placement, 10/68 (15%) infants had a decrease in mean HR by >10 beats per minute (bpm) compared with their individual baseline mean HR in the 15 s before facemask placement. In 4 (6%) infants, HR decreased to <100 bpm. Nine out of 68 (13%) infants had an increase in mean HR by >10 bpm; 7 of these infants had a baseline HR <120 bpm. In univariable comparisons, the following characteristics were found not to be risk factors for a decrease in HR by >10 bpm: prematurity; type of respiratory support; hypoxaemia; early cord clamping; mode of birth; HR <120 bpm before mask placement. Six out of 63 infants (10%) who had HR ≥120 bpm after facemask placement had a late decrease in HR to <100 bpm between 30 and 120 s after facemask placement. CONCLUSION: Facemask respiratory support at birth is temporally associated with a decrease in HR in a subset of late-preterm and term infants.
Subject(s)
Infant, Premature , Masks , Infant, Newborn , Pregnancy , Female , Humans , Infant , Heart Rate/physiology , Masks/adverse effects , Infant, Premature/physiology , Electrocardiography , AustraliaABSTRACT
Neutropenic patients with bacteraemia need prolonged intravenous antibiotic treatment. Using cytometric bead array technology, we show in children with febrile neutropenia that bacteraemia is associated with an elevation of at least 1 of 3 plasma cytokines plus C-reactive protein. The combination of interleukin (IL)-8, IL-6, IL-10, and C-reactive protein values above operator-defined cutoff levels identified 15 of 16 episodes of bacteraemia, making this a potentially useful technique in identifying high-risk patients who should not be discharged early from hospital. Furthermore, low risk of bacteraemia may be predicted by a combination of below threshold cytokines and negative clinical examination.
Subject(s)
Bacteremia/etiology , Cytokines/blood , Fever/immunology , Flow Cytometry/methods , Neoplasms/complications , Neutropenia/immunology , Bacteremia/immunology , C-Reactive Protein/analysis , Child , HumansABSTRACT
BACKGROUND: The feasibility and benefits of continuous sustained inflations (SIs) during chest compressions (CCs) during delayed cord clamping (physiological-based cord clamping; PBCC) are not known. We aimed to determine whether continuous SIs during CCs would reduce the time to return of spontaneous circulation (ROSC) and improve post-asphyxial blood pressures and flows in asystolic newborn lambs. METHODS: Fetal sheep were surgically instrumented immediately prior to delivery at ~139 days' gestation and asphyxia induced until lambs reached asystole. Lambs were randomised to either immediate cord clamping (ICC) or PBCC. Lambs then received a single SI (SIsing; 30 s at 30 cmH2O) followed by intermittent positive pressure ventilation, or continuous SIs (SIcont: 30 s duration with 1 s break). We thus examined 4 groups: ICC +SIsing, ICC +SIcont, PBCC +SIsing, and PBCC +SIcont. Chest compressions and epinephrine administration followed international guidelines. PBCC lambs underwent cord clamping 10 min after ROSC. Physiological and oxygenation variables were measured throughout. RESULTS: The time taken to achieve ROSC was not different between groups (mean (SD) 4.3±2.9 min). Mean and diastolic blood pressure was higher during chest compressions in PBCC lambs compared with ICC lambs, but no effect of SIs was observed. SIcont significantly reduced pulmonary blood flow, diastolic blood pressure and oxygenation after ROSC compared with SIsing. CONCLUSION: We found no significant benefit of SIcont over SIsing during CPR on the time to ROSC or on post-ROSC haemodynamics, but did demonstrate the feasibility of continuous SIs during advanced CPR on an intact umbilical cord. Longer-term studies are recommended before this technique is used routinely in clinical practice.
Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Insufflation , Animals , Animals, Newborn , Asphyxia , Cardiopulmonary Resuscitation/methods , Constriction , Insufflation/methods , SheepABSTRACT
OBJECTIVE: Intraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous with intravenous epinephrine administration during resuscitation of severely asphyxiated lambs at birth. METHODS: Near-term lambs (139 days' gestation) were instrumented antenatally for measurement of carotid and pulmonary blood flow and systemic blood pressure. Intrapartum asphyxia was induced by umbilical cord clamping until asystole. Resuscitation commenced with positive pressure ventilation followed by chest compressions and the lambs received either intraosseous or central intravenous epinephrine (10 µg/kg); epinephrine administration was repeated every 3 min until return of spontaneous circulation (ROSC). The lambs were maintained for 30 min after ROSC. Plasma epinephrine levels were measured before cord clamping, at end asphyxia, and at 3 and 15 min post-ROSC. RESULTS: ROSC was successful in 7 of 9 intraosseous epinephrine lambs and in 10 of 12 intravenous epinephrine lambs. The time and number of epinephrine doses required to achieve ROSC were similar between the groups, as were the achieved plasma epinephrine levels. Lambs in both groups displayed a similar marked overshoot in systemic blood pressure and carotid blood flow after ROSC. Blood gas parameters improved more quickly in the intraosseous lambs in the first 3 min, but were otherwise similar over the 30 min after ROSC. CONCLUSIONS: Intraosseous epinephrine administration results in similar outcomes to intravenous epinephrine during resuscitation of asphyxiated newborn lambs. These findings support the inclusion of intraosseous access as a route for epinephrine administration in current guidelines.
Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Hypoxia-Ischemia, Brain , Animals , Animals, Newborn , Asphyxia/therapy , Cardiopulmonary Resuscitation/methods , Epinephrine , Humans , Infant, Newborn , Resuscitation/methods , SheepABSTRACT
Background: Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration. Methods: Deceased near-term newborn lambs (139 days gestation, term â¼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0-50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges. Results: All LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r 2 = 0.71). Conclusion: LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.
ABSTRACT
OBJECTIVE: To identify risk factors associated with delivery room respiratory support in at-risk infants who are initially vigorous and received delayed cord clamping (DCC). DESIGN: Prospective cohort study. SETTING: Two perinatal centres in Melbourne, Australia. PATIENTS: At-risk infants born at ≥35+0 weeks gestation with a paediatric doctor in attendance who were initially vigorous and received DCC for >60 s. MAIN OUTCOME MEASURES: Delivery room respiratory support defined as facemask positive pressure ventilation, continuous positive airway pressure and/or supplemental oxygen within 10 min of birth. RESULTS: Two hundred and ninety-eight infants born at a median (IQR) gestational age of 39+3 (38+2-40+2) weeks were included. Cord clamping occurred at a median (IQR) of 128 (123-145) s. Forty-four (15%) infants received respiratory support at a median of 214 (IQR 156-326) s after birth. Neonatal unit admission for respiratory distress occurred in 32% of infants receiving delivery room respiratory support vs 1% of infants who did not receive delivery room respiratory support (p<0.001). Risk factors independently associated with delivery room respiratory support were average heart rate (HR) at 90-120 s after birth (determined using three-lead ECG), mode of birth and time to establish regular cries. Decision tree analysis identified that infants at highest risk had an average HR of <165 beats per minute at 90-120 s after birth following caesarean section (risk of 39%). Infants with an average HR of ≥165 beats per minute at 90-120 s after birth were at low risk (5%). CONCLUSIONS: We present a clinical decision pathway for at-risk infants who may benefit from close observation following DCC. Our findings provide a novel perspective of HR beyond the traditional threshold of 100 beats per minute.
Subject(s)
Critical Pathways/standards , Delivery, Obstetric , Electrocardiography/methods , Oxygen Inhalation Therapy , Umbilical Cord , Australia/epidemiology , Cesarean Section/adverse effects , Cesarean Section/methods , Clinical Decision-Making , Constriction , Continuous Positive Airway Pressure/methods , Delivery, Obstetric/adverse effects , Delivery, Obstetric/methods , Delivery, Obstetric/statistics & numerical data , Female , Gestational Age , Heart Rate , Humans , Infant, Newborn , Male , Monitoring, Physiologic/methods , Oxygen Inhalation Therapy/adverse effects , Oxygen Inhalation Therapy/instrumentation , Oxygen Inhalation Therapy/methods , Risk Assessment/methods , Risk Factors , Time-to-Treatment/standards , Time-to-Treatment/statistics & numerical dataABSTRACT
INTRODUCTION: Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants. METHODS: Infants born at <320/7 weeks were prospectively enrolled at 2 centres. LUS videos of both sides of the chest were obtained 5-10â¯min, 11-20â¯min, and 1-3â¯h after birth. Clinicians were masked to the results of the LUS assessment and surfactant therapy was provided according to local guidelines. LUS videos were graded blinded to clinical data. Presence of unilateral type 1 ('whiteout') LUS or worse was considered test positive. Receiver Operating Characteristic (ROC) analysis compared the accuracy of LUS and an FiO2 threshold of 0.3 to predict subsequent surfactant therapy. RESULTS: Fifty-two infants with a median age of 276/7 weeks (IQR 260/7-286/7) were studied. Thirty infants (58%) received surfactant. Area under the ROC curve (AUC) for LUS at 5-10â¯min, 11-20â¯min and 1-3â¯h was 0.78 (95% CI, 0.66-0.90), 0.76 (95% CI, 0.65-0.88) and 0.86 (95% CI, 0.75-0.97) respectively, outperforming FiO2 at the 5-10â¯min timepoint (AUC 0.45, 95% CI 0.29-0.62, pâ¯=â¯0.001). At 11-20â¯min, LUS had a specificity of 95% (95% CI 77-100%) and sensitivity of 59% (95% CI, 39-77%) to predict surfactant therapy. All infants born at 23-276/7 weeks with LUS test positive received surfactant. Twenty-six infants (50%) had worsening of LUS grades on serial assessment. CONCLUSIONS: LUS in the delivery room and accurately predicts surfactant therapy in infants <320/7 weeks.
Subject(s)
Infant, Extremely Premature , Respiratory Distress Syndrome, Newborn , Humans , Infant , Infant, Newborn , Lung/diagnostic imaging , Prospective Studies , Respiratory Distress Syndrome, Newborn/diagnostic imaging , Respiratory Distress Syndrome, Newborn/drug therapy , Surface-Active Agents , UltrasonographyABSTRACT
BACKGROUND: Studies using conventional consoles have suggested a possible link between video-gaming and laparoscopic skill. The authors hypothesized that the Nintendo Wii, with its motion-sensing interface, would provide a better model for laparoscopic tasks. This study investigated the relationship between Nintendo Wii skill, prior gaming experience, and laparoscopic skill. METHODS: In this study, 20 participants who had minimal experience with either laparoscopic surgery or Nintendo Wii performed three tasks on a Webcam-based laparoscopic simulator and were assessed on three games on the Wii. The participants completed a questionnaire assessing prior gaming experience. RESULTS: The score for each of the three Wii games correlated positively with the laparoscopic score (r = 0.78, 0.63, 0.77; P < 0.001), as did the combined Wii score (r = 0.82; P < 0.001). The participants in the top tertile of Wii performance scored 60.3% higher on the laparoscopic tasks than those in the bottom tertile (P < 0.01). Partial correlation analysis with control for the effect of prior gaming experience showed a significant positive correlation between the Wii score and the laparoscopic score (r = 0.713; P < 0.001). Prior gaming experience also correlated positively with the laparoscopic score (r = 0.578; P < 0.01), but no significant difference in the laparoscopic score was observed when the participants in the top tertile of experience were compared with those in the bottom tertile (P = 0.26). CONCLUSIONS: The study findings suggest a skill overlap between the Nintendo Wii and basic laparoscopic tasks. Surgical candidates with advanced Nintendo Wii ability may possess higher baseline laparoscopic ability.