Randomised trial of epinephrine dose and flush volume in term newborn lambs.

OBJECTIVES: Neonatal resuscitation guidelines recommend 0.5-1 mL saline flush following 0.01-0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest. DESIGN: Forty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored. RESULTS: Ten lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush. CONCLUSIONS: 0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

Perinatal Hypophosphatasia in a Premature Infant.

A premature male infant was delivered at 32 weeks' gestation due to category-2 fetal tracing after preterm labor. The physical exam showed shortened and bowed long bones, with calvarium felt in small area of the head. Serum alkaline phosphatase was very low on admission. Extensive metaphyseal abnormalities, bowing of long bones, and poor ossification of all bones were noted on skeletal survey (radiography). Based on ultrasound evidence of "bowing" and long bone fractures at 26 weeks, amniocentesis was performed that later diagnosed hypophosphatasia by genetic testing while ruling out osteogenesis imperfecta. Although ventilated initially, the infant gradually improved with enzyme replacement therapy (ERT) and was extubated to noninvasive ventilation for 6 weeks. Following clinical deterioration with hypoxic respiratory failure secondary to sepsis at 4 months of age, he succumbed to severe pulmonary hypertension, likely secondary to chronic lung disease and prolonged ventilation. Early diagnosis allowed timely initiation of appropriate therapy. Radiological improvement with the therapy showed promising results in this rare disease. Despite specific novel therapy being available, variability in presentation dictates prognosis in this previously universally fatal condition. The potential unknown effects of ERT on pulmonary vascular remodeling need further investigation.

Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration.

BACKGROUND: The Neonatal Resuscitation Program (NRP) recommends upper and lower limits of preductal saturations (SpO2) extrapolated from studies in infants resuscitated in room air. These limits have not been validated in asphyxia and lung disease. METHODS: Seven control term lambs delivered by cesarean section were ventilated with 21% O2. Thirty lambs with asphyxia with meconium aspiration were randomly assigned to resuscitation with 21% O2 (n = 6), 100% O2 (n = 6), or initiation with 21% O2 followed by variable FIO2 to maintain NRP target SpO2 ranges (n = 18). Hemodynamic and ventilation parameters were recorded for 15 min. RESULTS: Control lambs maintained preductal SpO2 near the lower limit of NRP target range. Asphyxiated lambs had low SpO2 (38 ± 2%), low arterial pH (6.99 ± 0.01), and high PaCO2 (96 ± 7 mm Hg) at birth. Resuscitation with 21% O2 resulted in SpO2 values below the target range with low pulmonary blood flow (Qp) compared to variable FIO2 group. The increase in PaO2 and Qp with variable FIO2 resuscitation was similar to control lambs. CONCLUSION: Maintaining SpO2 as recommended by NRP by actively adjusting inspired O2 leads to effective oxygenation and higher Qp in asphyxiated lambs with lung disease. Our findings support the current NRP SpO2 guidelines for O2 supplementation during resuscitation of an asphyxiated neonate.

Oxygen saturation index and severity of hypoxic respiratory failure.

BACKGROUND: The oxygenation index (OI = mean airway pressure, MAP × FiO2 × 100 : PaO2) is used to assess the severity of hypoxic respiratory failure (HRF) and persistent pulmonary hypertension of the newborn (PPHN). An indwelling arterial line or arterial punctures are necessary to obtain PaO2 for the calculation of OI. Oxygenation can be continuously and noninvasively assessed using pulse oximetry. The use of the oxygen saturation index (OSI = MAP × FiO2 × 100 : SpO2) can be an alternate method of assessing the severity of HRF. OBJECTIVE: To evaluate the correlation between OSI and OI in the following: (1) neonates with HRF and (2) a lamb model of meconium aspiration syndrome. METHODS: Human neonates: a retrospective chart review of 74 ventilated late preterm/term neonates with indwelling arterial access and SpO2 values in the first 24 h of life was conducted. OSI and OI were calculated and correlated. Lamb model: arterial blood gases were drawn and preductal SpO2 was documented in 40 term newborn lambs with asphyxia and meconium aspiration. OI and OSI were calculated and correlated with pulmonary vascular resistance (PVR). RESULTS: Mean values of OSI and OI showed a correlation coefficient of 0.952 in neonates (mean value of 308 observations in 74 neonates) and 0.948 in lambs (mean value of 743 observations in 40 lambs). In lambs, with increasing PVR, there was a decrease in OI and OSI. CONCLUSION: OSI correlates significantly with OI in infants with HRF. This noninvasive measure may be used to assess the severity of HRF and PPHN in neonates without arterial access.