273 - Optimal approach to perinatal acidosis in birth asphyxia with PPHN

Publication Number: 4269.273

Paulina Hume, University of California Davis Children's Hospital, Sacramento, CA, United States; Sylvia Bowditch, University of California Davis Children's Hospital, Sacramento, CA, United States; Deepika Sankaran, University of California Davis Children's Hospital, Sacramento, CA, United States; Evan M. Giusto, UC Davis Health, Sacramento, CA, United States; Payam Vali, University of California, Davis, School of Medicine, sacramento, CA, United States; Amy Lesneski, UC Davis, Davis, CA, United States; Rebecca Valdez, University of California Davis Children's Hospital, Sacramento, CA, United States; Evan Maher, University of California, Davis, School of Medicine, Woodland, CA, United States; Victoria Hammitt, UC Davis Stem Cell Research, Davis, CA, United States; Michelle J. Lim, University of California, Davis, School of Medicine, Sacramento, CA, United States; Satyan Lakshminrusimha, UC Davis, Sacramento, CA, United States

Background: Metabolic acidosis is commonly associated with birth asphyxia and hypoxic ischemic encephalopathy (HIE). Persistent pulmonary hypertension (PPHN) is often secondary to meconium aspiration syndrome (MAS) and is seen in nearly a quarter of neonates with moderate-to-severe HIE. Metabolic acidosis can increase pulmonary vascular resistance and worsen PPHN. Large doses of sodium bicarbonate (NaHCO3) were previously used to correct severe metabolic acidosis but are associated with harmful effects including alterations in cerebral and pulmonary blood flow. More recently, boluses of lactated Ringer (LR) or 0.9% saline (NS) are used to improve perfusion and correct acidosis. The acute effects of slow infusion of smaller doses of NaHCO3 or boluses of LR or NS on pH, cerebral and pulmonary hemodynamics remain unknown.

Objective: To evaluate the effect of an infusion of NaHCO3, LR or NS over 30 mins on cerebral and pulmonary hemodynamics, and pH in an ovine model of MAS+PPHN+HIE.

Design/Methods: Asphyxia was induced by meconium instillation and umbilical cord occlusion in 134-139 day gestation lambs and subjected to therapeutic hypothermia. Lambs were randomized to receive NaHCO3 (1 mEq/kg), LR (10 ml/kg) and NS (10 ml/kg) in a random sequence over 30 mins when metabolic acidosis (pH < 7.25 or a base deficit > -10 mEq/L) was observed. Following recovery, the lambs were ventilated targeting PaCO2 (45-60 mmHg). Invasive hemodynamics (left carotid artery flow-CaF and left pulmonary arterial blood flow-LPA flow) and blood gas parameters were monitored.

Results: The baseline characteristics were similar between the lambs included in the study. The CaF and LPA flow were not different at 30, 60 and 90 min after infusion of NaHCO3, LR and NS, respectively (figures 1, 2). pH was not significantly different between the groups (figure 3).

Conclusion(s): In an ovine model of MAS, PPHN and metabolic acidosis, slow infusion of 1 mEq/kg of NaHCO3 was not associated with adverse effects on cerebral or pulmonary blood flow. Further studies are needed to investigate the safety of slow infusion of small doses of NaHCO3 to correct metabolic acidosis in the NICU.

Fig 1. Change in Carotid Artery Flow with Sodium Bicarbonate, LR, and NS, respectively
Observed carotid artery flow over time in lambs administered sodium bicarbonate, LR, and NS in random sequence. Values indicate relative change from baseline over 30 minute intervals. Two-way ANOVA performed on bolus and time.

Fig 2. Change in LPA Flow with Sodium Bicarbonate, LR, and NS, respectively
Observed LPA flow over time in lambs administered sodium bicarbonate, LR, and NS in random sequence. Values indicate relative change from baseline over 30 minute intervals. Two-way ANOVA performed on bolus and time.

Fig 3. Change in pH with Sodium Bicarbonate, LR, and NS, respectively
Observed pH over time in lambs administered sodium bicarbonate, LR, and NS in random sequence. Values indicate absolute values over 30 minute intervals. Student t-test comparing significance of means at 60 min intervals and baseline.