Endotracheal epinephrine at standard versus high dose for resuscitation of asystolic newborn lambs.

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.

Protective ventilation of preterm lambs exposed to acute chorioamnionitis does not reduce ventilation-induced lung or brain injury.

BACKGROUND: The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. METHODS: Pregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. RESULTS: LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. CONCLUSIONS: Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.

Post-implementation review of pulse oximetry screening of well newborns in an Australian tertiary maternity hospital.

AIM: Despite there being evidence that pulse oximetry screening is better than clinical examination alone in early detection of CHD, implementation has been slow. The aim of this paper was to evaluate the practice after its implementation into routine care at Royal Prince Alfred Hospital in 2008. METHODS: A single pulse oximetry measurement was incorporated in the routine discharge newborn examination or, with early discharge, as a part of the Midwife Discharge Support Programme. An oxygen saturation level greater than or equal to 95% was considered normal, and a level less than 95%, confirmed on a repeat measure, triggered a review and examination by a consultant neonatal paediatrician. The saturation levels were recorded in the hospital database. Ascertainment of major CHD requiring surgery in the first 12 months was performed by searching the cardiac surgery database of the Heart Centre for Children. RESULTS: A total of 18 801 babies were screened over a 42-month period. Of these, four babies with major CHD were diagnosed prior to discharge with the main clinical alert resulting from routine pulse oximetry screening (true positive). Of the 11 cases with saturation <95% but no CHD (false positive cases), six had respiratory pathology. One baby with normal saturation level needed surgery in the first year for a large ventricular septal defect (false negative). The false positive rate of pulse oximetry screening for CHD was 0.13% with sensitivity 80%, specificity of 99.8%, a positive predictive value of 13.3% and a negative predictive value of 99.9%. Nine additional echocardiogram were required over 42 months. CONCLUSIONS: These post-implementation data confirm that pulse oximetry screening increases early diagnosis of major CHD as well as other important pathology with a very low false positive rate and minimal requirement for extra echocardiograms. Pulse oximetry screening of apparently well newborns should become a standard of care.

Use of ultrasound in the haemodynamic assessment of the sick neonate.

Clinician performed ultrasound (CPU) by the clinician caring for a sick patient is increasingly used in critical care specialties. The real-time haemodynamic information obtained helps the clinician to understand underlying physiology, target treatment and refine clinical decision-making. Neonatologists are increasingly using ultrasound to assess sick neonates with a range of clinical presentations and demand for training and accreditation programmes is increasing. This review discusses the current expanded uses for CPU in the haemodynamic assessment of the sick neonate.

Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs.

Delayed cord clamping improves circulatory stability in preterm infants at birth, but the underlying physiology is unclear. We investigated the effects of umbilical cord clamping, before and after ventilation onset, on cardiovascular function at birth. Prenatal surgery was performed on lambs (123 days) to implant catheters into the pulmonary and carotid arteries and probes to measure pulmonary (PBF), carotid (CaBF) and ductus arteriosus blood flows. Lambs were delivered at 126 ± 1 days and: (1) the umbilical cord was clamped at delivery and ventilation was delayed for about 2 min (Clamp 1st; n = 6), and (2) umbilical cord clamping was delayed for 3-4 min, until after ventilation was established (Vent 1st; n = 6). All lambs were subsequently ventilated for 30 min. In Clamp 1st lambs, cord clamping rapidly (within four heartbeats), but transiently, increased pulmonary and carotid arterial pressures (by ∼30%) and CaBF (from 30.2 ± 5.6 to 40.1 ± 4.6 ml min(-1) kg(-1)), which then decreased again within 30-60 s. Following ventilation onset, these parameters rapidly increased again. In Clamp 1st lambs, cord clamping reduced heart rate (by ∼40%) and right ventricular output (RVO; from 114.6 ± 14.4 to 38.8 ± 9.7 ml min(-1) kg(-1)), which were restored by ventilation. In Vent 1st lambs, cord clamping reduced RVO from 153.5 ± 3.8 to 119.2 ± 10.6 ml min(-1) kg(-1), did not affect heart rates and resulted in stable blood flows and pressures during transition. Delaying cord clamping for 3-4 min until after ventilation is established improves cardiovascular function by increasing pulmonary blood flow before the cord is clamped. As a result, cardiac output remains stable, leading to a smoother cardiovascular transition throughout the early newborn period.

Variation in the management of persistent pulmonary hypertension of the newborn: a survey of physicians in Canada, Australia, and New Zealand.

BACKGROUND: Despite advances in management of persistent pulmonary hypertension of the newborn (PPHN), the risk of mortality and adverse neurological sequelae remains high. Characterizing variation in practices is a crucial step toward improved patient outcome. OBJECTIVE: Evaluate intensive care practices in Canada and the Australia-New Zealand region (AUS-NZ). METHODS: A prospective cross-sectional online survey of neonatologists was conducted. A 35-item questionnaire was developed, validated, and piloted to collect information on diagnosis, inhaled nitric oxide (iNO) practices, alternative vasodilators or cardiotropes, and echocardiography. Variation among survey respondents as well as intergroup comparison was performed. RESULTS: Data were collected from 217 respondents. Echocardiography and arterial blood gas were the most common diagnostic tests to assess the severity of PPHN. iNO administration is more frequently scrutinized in Canada (36% versus 10% [AUS-NZ], p < 0.001). Canadian physicians reported higher use of intravenous milrinone (p < 0.001), vasopressin (p = 0.02), and inhaled prostacyclin (p = 0.02), but lower use of sildenafil (p = 0.01) for refractory pulmonary hypertension. A greater proportion of neonatologists in AUS-NZ were trained to perform echocardiography (p < 0.001) to optimize treatment decisions. CONCLUSION: Wide variation exists in the management of PPHN. There is a need to provide more guidance regarding principles of management in PPHN, while recognizing the dynamic nature of cardiopulmonary physiology in individual patients.

The cardiopulmonary haemodynamic transition at birth is not different between male and female preterm lambs.

Males born preterm are at greater risk of illness and death than females, principally due to respiratory disease. Much of the excess morbidity occurs within the first few hours of life. Therefore, the aim of the present study was to investigate whether or not differences in the cardiopulmonary transition soon after birth underlie the increased morbidity in males after preterm birth. Nine female and thirteen male lambs (128±2 days gestation) underwent surgery immediately before delivery for implantation of a pulmonary arterial flow-probe and catheters into the main pulmonary artery and a carotid artery. After birth lambs were ventilated for 30 min (tidal volume 7 mL kg(-1)) while anaesthetised. Arterial pressures and flows were recorded in real time and left-ventricular output measured using Doppler echocardiography. Before birth, fetal cardiopulmonary haemodynamics, arterial blood gases, pH, glucose and lactate did not differ between sexes. Similarly, in the neonatal period there were no significant differences in arterial blood gas status, ventilation parameters, respiratory indices or cardiopulmonary haemodynamics between the sexes. Our data show that the cardiopulmonary transition at birth in ventilated, anaesthetised preterm lambs is not influenced by sex. Thus, the neonatal 'male disadvantage' is not explained by an impaired cardiovascular transition at birth.

Nitric oxide in preterm infant with pulmonary hypoplasia.

Premature infants with hypoplastic lungs may have elevated pulmonary vascular resistance with right to left shunt across ductus arteriosus and/or foramen ovale. Inhaled nitric oxide (NO) being selective pulmonary vasodilator without significant effects on systemic circulation can potentially reverse this shunt. The authors herewith report a case of a premature infant with severe hypoxemic respiratory failure after preterm premature prolonged rupture of membranes leading to oligohydramnios and pulmonary hypoplasia that was treated successfully with NO and describe the neurodevelopmental outcome at 1 year of age.