Abstract
Objective
To determine the safety and effectiveness of sodium bicarbonate administration in the management of metabolic acidemia and short-term outcomes in neonates with hypoxic-ischemic encephalopathy (HIE).
Study design
Retrospective cohort study of neonates born at ≥35 weeks of gestation and receiving therapeutic hypothermia. Demographics, pH, lactate, base deficit, treatment, MRI findings, seizure incidence, death prior to discharge were collected.
Results
There was higher mortality (p = 0.010) and injury on MRI (p = 0.008)—primarily deep gray matter (p < 0.001) and cortical injury (p = 0.003)—in the bicarbonate group compared to controls in univariate analysis. The combined outcome of death or abnormal MRI was not significantly associated (OR 1.97, 95% CI 0.80–4.87, p = 0.141) with bicarbonate administration when adjusting for sex, 5-minute Apgar, and initial base deficit.
Conclusion
This study demonstrated association between bicarbonate use after HIE and negative short-term outcomes. Future prospective trials could overcome the treatment bias limitation demonstrated in this retrospective study.
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Data availability
The de-identified dataset generated and analyzed in the current study is available from the corresponding author on reasonable request.
References
Lee ACC, Kozuki N, Blencowe H, Vos T, Bahalim A, Darmstadt GL.et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74 Suppl 1:50–72.
Davidson JO, Wassink G, van den Heuij LG, Bennet L, Gunn AJ. Therapeutic hypothermia for neonatal Hypoxic–Ischemic encephalopathy – where to from here? Front Neurol. 2015;6:198.
Jacobs SE, Berg M, Hunt R, Tarnow‐Mordi WO, Inder TE, Davis PG, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Libr. 2013;2013:CD003311.
Van Anh TN, Hao TK, Chi NTD, Son NH. Predictions of hypoxic-ischemic encephalopathy by umbilical cord blood lactate in newborns with birth asphyxia. Open access Macedonian J Med Sci. 2019;7:3564–7.
Magistretti P, Allaman I. A cellular perspective on brain energy metabolism and functional imaging. Neuron (Camb, Mass) 2015;86:883–901.
Tassinari I, de Fraga L. Potential use of lactate for the treatment of neonatal hypoxic-ischemic encephalopathy. Neural Regeneration Res. 2022;17:788–90.
Aschner JL, Poland RL. Sodium bicarbonate: basically useless therapy. Pediatrics (Evanst). 2008;122:831–5.
Nair J, Kumar VHS. Current and emerging therapies in the management of hypoxic ischemic encephalopathy in neonates. Child (Basel). 2018;5:99.
Massenzi L, Aufieri R, Donno S, Agostino R, Dotta A. Use of intravenous sodium bicarbonate in neonatal intensive care units in italy: a nationwide survey. Ital J Pediatrics. 2021;47:63.
Shankaran S, Pappas A, Laptook AR, McDonald SA, Ehrenkranz RA, Tyson JE, et al. Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy. Pediatrics (Evanst). 2008;122:e791–8.
Westgate J, Garibaldi JM, Greene KR. Umbilical cord blood gas analysis at delivery: a time for quality data. BJOG: Int J Obstet Gynaecol. 1994;101:1054–63.
Kallet R, Jasmer R, Luce J, Lin L, Marks J. The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM). Am J Respiratory Crit Care Med. 2000;161:1149–53.
Allen KA, Brandon DH. Hypoxic ischemic encephalopathy: Pathophysiology and experimental treatments. Newborn Infant Nurs Rev. 2011;11:125–33.
Remzső G, Németh J, Varga V, Kovács V, Tóth-Szűki V, Kaila K, et al. Brain interstitial pH changes in the subacute phase of hypoxic-ischemic encephalopathy in newborn pigs. PLOS ONE. 2020;15:e0233851.
Forni LG, Hodgson LE, Selby NM. The janus faces of bicarbonate therapy in the ICU: not sure. Intensive Care Med. 2020;46:522–4.
Gehlbach BK, Schmidt GA. Bench-to-bedside review: Treating acid-base abnormalities in the intensive care unit-the role of buffers. Crit Care. 2004;8:259–65.
Mathieu D, Neviere R, Billard V, Fleyfel M, Wattel F. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: A prospective, controlled clinical study. Crit Care Med. 1991;19:1352–6.
Mochizuki K, Fujii T, Paul E, Anstey M, Pilcher DV, Bellomo R. Early metabolic acidosis in critically ill patients: a binational multicentre study. Crit Care Resuscitation. 2021;23:67–75.
Zhang Z, Zhu C, Mo L, Hong Y. Effectiveness of sodium bicarbonate infusion on mortality in septic patients with metabolic acidosis. Intensive Care Med. 2018;44:1888–95.
Shah S, Tracy M, Smyth J. Postnatal lactate as an early predictor of short-term outcome after intrapartum asphyxia. J Perinatol. 2004;24:16–20.
Rudnick MR, Blair GJ, Kuschner WG, Barr J. Lactic acidosis and the role of sodium bicarbonate: a narrative opinion. Shock (Augusta, Ga) 2020;53:528–36.
Ros J, Pecinska N, Alessandri B, Landolt H, Fillenz M. Lactate reduces glutamate-induced neurotoxicity in rat cortex. J Neurosci. 2001;66:790–4.
Roumes H, Dumont U, Sanchez S, Mazuel L, Blanc J, Raffard G, et al. Neuroprotective role of lactate in rat neonatal hypoxia-ischemia. J Cereb Blood Flow Metab. 2021;41:342–58.
Gupta BD, Sharma P, Bagla J, Parakh M, Soni JP. Renal failure in asphyxiated neonates. Indian Pediatrics. 2005;42:928–34.
Rhee CJ, da Costa CS, Austin T, Brady KM, Czosnyka M, Lee JK. Neonatal cerebrovascular autoregulation. Pediatr Res. 2018;84:602–10.
Massaro AN, Govindan RB, Vezina G, Chang T, Andescavage NN, Wang Y, et al. Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. J Neurophysiol. 2015;114:818–24.
Segar JL, Chock VY, Harer MW, Selewski DT, Askenazi DJ. Fluid management, electrolytes imbalance and renal management in neonates with neonatal encephalopathy treated with hypothermia. Semin Fetal Neonatal Med. 2021;26:101261.
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ESP and ET contributed to study design, interpretation of the data, drafted the initial manuscript, and reviewed and critically revised the manuscript. ERL performed the analysis, contributed to interpretation of the data, and reviewed and critically revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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This study was approved by the University of Nebraska Medical Center Institutional Review Board (0205-22-EX) with waiver of consent.
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Thuo, E., Lyden, E.R. & Peeples, E.S. Effect of early clinical management on metabolic acidemia in neonates with hypoxic-ischemic encephalopathy. J Perinatol (2024). https://doi.org/10.1038/s41372-024-02005-2
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DOI: https://doi.org/10.1038/s41372-024-02005-2