Bobby Mathew

Pulmonary hemodynamics in neonatal lambs resuscitated with 21%, 50%, and 100% oxygen.

The effect of resuscitation with varying levels of O2 on pulmonary hemodynamics at birth is not well known. We hypothesized that the decrease in pulmonary vascular resistance (PVR) and subsequent response to pulmonary vasoconstrictors and vasodilators will differ following resuscitation with 21%, 50%, or 100%O2 for 30 min at birth in normal term lambs. Lambs at 141 d gestation were delivered by cesarean section and ventilated with 21% (21% Res; n = 6), 50% (50% Res; n = 6), or 100% O2 (100% Res; n = 7) for 30 min followed by ventilation with 21% O2 in all three groups. A greater decrease in PVR was seen with 50% and 100% O2 ventilation than with 21% O2 (0.21 ± 0.02, 0.21 ± 0.02, and 0.34 ± 0.05 mm Hg/mL/min/kg, respectively). Subsequent pulmonary vasoconstriction to hypoxia (10% O2) and the thromboxane analog U46619 (0.5 and 1 μg/kg/min) was similar in all three groups. After inducing a stable elevation in PVR with U46619, impaired pulmonary vasodilation to inhaled NO (59 ± 4, 65 ± 4, and 74 ± 5% of baseline PVR with 21, 50, and 100%Res, respectively) and acetylcholine infusion (67 ± 8, 75 ± 6, and 87 ± 4% of baseline PVR with 21, 50, and 100%Res, respectively) and rebound pulmonary hypertension following their withdrawal were observed in the 100%Res group. We conclude that, while ventilation with 100% O2 at birth results in a greater initial decrease in PVR, subsequent pulmonary vasodilation to NO/acetylcholine is impaired.

Oxygen targeting in preterm infants: a physiological interpretation.

Randomized controlled trials evaluating low-target oxygen saturation (SpO2:85% to 89%) vs high-target SpO2 (91% to 95%) have shown variable results regarding mortality and morbidity in extremely preterm infants. Because of the variation inherent to the accuracy of pulse oximeters, the unspecified location of probe placement, the intrinsic relationship between SpO2 and arterial oxygen saturation (SaO2) and between SaO2 and partial pressure of oxygen (PaO2) (differences in oxygen dissociation curves for fetal and adult hemoglobin), the two comparison groups could have been more similar than dissimilar. The SpO2 values were in the target range for a shorter period of time than intended due to practical and methodological constraints. So the studies did not truly compare ‘target SpO2 ranges’. In spite of this overlap, some of the studies did find signficant differences in mortality prior to discharge, necrotizing enterocolitis and severe retinopathy of prematurity. These differences could potentially be secondary to time spent beyond the target range (SpO2 <85 or >95%) and could be avoided with an intermediate but wider target SpO2 range (87% to 93%). In conclusion, significant uncertainty persists about the desired target range of SpO2 in extremely preterm infants. Further studies should focus on studying newer methods of assessing oxygenation and strategies to limit hypoxemia (<85% SpO2) and hyperoxemia (>95% SpO2).

Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated with 21 and 100% oxygen

An increase in oxygen tension is an important factor in decreasing pulmonary vascular resistance (PVR) at birth. Birth asphyxia results in acidosis and increased PVR. We determined the effect of resuscitation with 21 vs. 100% O(2) on pulmonary hemodynamics, pulmonary arterial (PA) reactivity, and oxidant stress in a lamb model of in utero asphyxia. Term fetal lambs were acutely asphyxiated by intrauterine umbilical cord occlusion for 10 min resulting in acidosis (pH 6.96 ± 0.05 and Pco(2) 103 ± 5 Torr), bradycardia, systemic hypotension, and increased PVR. Lambs were treated with 30 min of resuscitation with 21% or 100% O(2) (n = 6 each). Pa(O(2)) was significantly elevated with 100% O(2) resuscitation compared with 21% O(2) (430 ± 38 vs. 64 ± 8 Torr), but changes in pH and Pa(CO(2)) were similar. The 100% O(2) induced greater increase in pulmonary blood flow and decrease in PVR at 1 min of life, but subsequent values were similar to 21% O(2) group between 2 and 30 min of life. Oxygen uptake from the lung and systemic oxygen extraction was similar between the two groups. Pulmonary arteries showed increased staining for superoxide anions and increased contractility to norepinephrine following resuscitation with 100% O(2). The increased PA contractility induced by 100% O(2) was reversed by scavenging superoxide anions with superoxide dismutase and catalase. We conclude that resuscitation of asphyxiated lambs with 100% O(2) increases Pa(O(2)) but does not improve lung oxygen uptake, decrease PVR at 30 min, or increase systemic oxygen extraction ratios. Furthermore, 100% O(2) also induces oxidative stress and increases PA contractility. These findings support the new neonatal resuscitation guidelines recommending 21% O(2) for initial resuscitation of asphyxiated neonates.

Critical congenital heart disease screening by pulse oximetry in a neonatal intensive care unit

Objective:Critical congenital heart disease (CCHD) screening is effective in asymptomatic late preterm and term newborn infants with a low false-positive rate (0.035%). (1) To compare 2817 neonatal intensive care unit (NICU) discharges before and after implementation of CCHD screening; and (2) to evaluate CCHD screening at <35 weeks gestation.Study Design:Collection of results of CCHD screening including pre- and postductal pulse oximetry oxygen saturation (SpO2) values.Result:During the pre-CCHD screen period, 1247 infants were discharged from the NICU and one case of CCHD was missed. After 1 March 2012, 1508 CCHD screens were performed among 1570 discharges and no CCHDs were missed. The pre- and postductal SpO2 values were 98.8±1.4% and 99±1.3%, respectively, in preterm and 98.9±1.3% and 98.9±1.4%, respectively, in term infants. Ten infants had false-positive screens (10/1508=0.66%).Conclusion:Performing universal screening in the NICU is feasible but is associated with a higher false-positive rate compared with asymptomatic newborn infants.

Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide

Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in one-third of patients with PPHN. Inhaled NO is less effective in the management of PPHN secondary to congenital diaphragmatic hernia (CDH), extreme prematurity, and bronchopulmonary dysplasia (BPD). Intravenous pulmonary vasodilators such as prostacyclin, alprostadil, sildenafil, and milrinone have been successfully used in PPHN resistant to iNO. Oral pulmonary vasodilators such as endothelin receptor antagonist bosentan and phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are used both during acute and chronic phases of PPHN. In the absence of infection, glucocorticoids may also be effective in PPHN. Many of these pharmacologic agents are not approved for use in PPHN and our knowledge is based on case reports and small trials. Large multicenter randomized controlled trials with long-term follow-up are required to evaluate alternate pharmacologic strategies in PPHN.

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.

Tracheal suctioning improves gas exchange but not hemodynamics in asphyxiated lambs with meconium aspiration

Background:Current neonatal resuscitation guidelines recommend tracheal suctioning of nonvigorous neonates born through meconium-stained amniotic fluid.Methods:We evaluated the effect of tracheal suctioning at birth in 29 lambs with asphyxia induced by cord occlusion and meconium aspiration during gasping.Results:Tracheal suctioning at birth (n = 15) decreased amount of meconium in distal airways (53 ± 29 particles/mm2 lung area) compared to no suction (499 ± 109 particles/mm2; n = 14; P < 0.001). Three lambs in the suction group had cardiac arrest during suctioning, requiring chest compressions and epinephrine. Onset of ventilation was delayed in the suction group (146 ± 11 vs. 47 ± 3 s in no-suction group; P = 0.005). There was no difference in pulmonary blood flow, carotid blood flow, and pulmonary or systemic blood pressure between the two groups. Left atrial pressure was significantly higher in the suction group. Tracheal suctioning resulted in higher Pao2/FiO2 levels (122 ± 21 vs. 78 ± 10 mm Hg) and ventilator efficiency index (0.3 ± 0.05 vs.0.16 ± 0.03). Two lambs in the no-suction group required inhaled nitric oxide. Lung 3-nitrotyrosine levels were higher in the suction group (0.65 ± 0.03 ng/µg protein) compared with the no-suction group (0.47 ± 0.06).Conclusion:Tracheal suctioning improves oxygenation and ventilation. Suctioning does not improve pulmonary/systemic hemodynamics or oxidative stress in an ovine model of acute meconium aspiration with asphyxia.

Neonatal resuscitation: evolving strategies

Birth asphyxia accounts for about 23% of the approximately 4 million neonatal deaths each year worldwide (Black et al., Lancet, 2010, 375(9730):1969-87). The majority of newborn infants require little assistance to undergo physiologic transition at birth and adapt to extrauterine life. Approximately 10% of infants require some assistance to establish regular respirations at birth. Less than 1% need extensive resuscitative measures such as chest compressions and approximately 0.06% require epinephrine (Wyllie et al. Resuscitation, 2010, 81 Suppl 1:e260–e287). Transition at birth is mediated by significant changes in circulatory and respiratory physiology. Ongoing research in the field of neonatal resuscitation has expanded our understanding of neonatal physiology enabling the implementation of improved recommendations and guidelines on how to best approach newborns in need for intervention at birth. Many of these recommendations are extrapolated from animal models and clinical trials in adults. There are many outstanding controversial issues in neonatal resuscitation that need to be addressed. This article provides a comprehensive and critical literature review on the most relevant and current research pertaining to evolving new strategies in neonatal resuscitation. The key elements to a successful neonatal resuscitation include ventilation of the lungs while minimizing injury, the judicious use of oxygen to improve pulmonary blood flow, circulatory support with chest compressions, and vasopressors and volume that would hasten return of spontaneous circulation. Several exciting new avenues in neonatal resuscitation such as delayed cord clamping, sustained inflation breaths, and alternate vasopressor agents are briefly discussed. Finally, efforts to improve resuscitative efforts in developing countries through education of basic steps of neonatal resuscitation are likely to decrease birth asphyxia and neonatal mortality.

Association between caffeine citrate exposure and necrotizing enterocolitis in preterm infants

PURPOSE The results of a case-control study of the potential role of caffeine citrate therapy in the development of necrotizing enterocolitis (NEC) are presented. METHODS Patient records for a 10-year period were reviewed to collect sufficient data to test the hypothesis that newborns treated in a hospitals perinatal intensive care unit for NEC might have had a higher cumulative exposure to caffeine citrate relative to that of neonates of similar postconceptional and postnatal age who did not develop NEC. Ninety-five cases of NEC were identified; each case was matched to a control case by gestational age and birth weight. To enable comparative analyses, each control was assigned an index date according to the number of days from birth to NEC diagnosis in the paired case. Data collected for analysis included patient demographics, information on caffeine citrate and concomitant medication use, and potential confounding factors. RESULTS Analysis of aggregated data for the entire seven-day NEC event timeframe indicated no significant differences between cases and controls with regard to average caffeine citrate loading doses (p = 0.5), cumulative exposure (p = 0.2), and trough serum concentrations (p = 0.5); mean cumulative exposure values differed significantly at one time point (four days prior to NEC diagnosis (p = 0.04). CONCLUSION Cumulative exposure to caffeine citrate among infants who developed NEC and infants who did not develop NEC differed significantly at only one of six evaluated time points during the seven days before NEC development or the index date. There was no significant difference between groups in the proportions of patients who received caffeine citrate or in mean serum caffeine concentrations.

Evaluation of Timing and Route of Epinephrine in a Neonatal Model of Asphyxial Arrest.

Background Epinephrine administered by low umbilical venous catheter (UVC) or endotracheal tube (ETT) is indicated in neonates who fail to respond to positive pressure ventilation and chest compressions at birth. Pharmacokinetics of ETT epinephrine via fluid‐filled lungs or UVC epinephrine in the presence of fetal shunts is unknown. We hypothesized that epinephrine administered by ETT or low UVC results in plasma epinephrine concentrations and rates of return of spontaneous circulation (ROSC) similar to right atrial (RA) epinephrine. Methods and Results Forty‐four lambs were randomized into the following groups: RA epinephrine (0.03 mg/kg), low UVC epinephrine (0.03 mg/kg), postcompression ETT epinephrine (0.1 mg/kg), and precompression ETT epinephrine (0.1 mg/kg). Asystole was induced by umbilical cord occlusion. Resuscitation was initiated following 5 minutes of asystole. Thirty‐eight of 44 lambs achieved ROSC (10/11, 9/11, and 12/22 in the RA, UVC, and ETT groups, respectively; subsequent RA epinephrine resulted in a total ROSC of 19/22 in the ETT groups). Median time (interquartile range) to achieve ROSC was significantly longer in the ETT group (including those that received RA epinephrine) compared to the intravenous group (4.5 [2.9–7.4] versus 2 [1.9–3] minutes; P=0.02). RA and low UVC epinephrine administration achieved comparable peak plasma epinephrine concentrations (470±250 versus 450±190 ng/mL) by 1 minute compared to ETT values of 130±60 ng/mL at 5 minutes; P=0.03. Following ROSC with ETT epinephrine alone, there was a delayed peak epinephrine concentration (652±240 ng/mL). Conclusions The absorption of ETT epinephrine is low and delayed at birth. RA and low UVC epinephrine rapidly achieve high plasma concentrations resulting in ROSC.