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Effect of early clinical management on metabolic acidemia in neonates with hypoxic-ischemic encephalopathy



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.


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.


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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Fig. 1
Fig. 2: Primary outcomes between the group receiving bicarbonate and those who did not (no treatment).

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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.


  1. Lee ACC, Kozuki N, Blencowe H, Vos T, Bahalim A, Darmstadt 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.

  2. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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.

    Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. Magistretti P, Allaman I. A cellular perspective on brain energy metabolism and functional imaging. Neuron (Camb, Mass) 2015;86:883–901.

    Article  CAS  Google Scholar 

  6. Tassinari I, de Fraga L. Potential use of lactate for the treatment of neonatal hypoxic-ischemic encephalopathy. Neural Regeneration Res. 2022;17:788–90.

    Article  CAS  Google Scholar 

  7. Aschner JL, Poland RL. Sodium bicarbonate: basically useless therapy. Pediatrics (Evanst). 2008;122:831–5.

    Article  Google Scholar 

  8. Nair J, Kumar VHS. Current and emerging therapies in the management of hypoxic ischemic encephalopathy in neonates. Child (Basel). 2018;5:99.

    Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. 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.

    Article  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. Allen KA, Brandon DH. Hypoxic ischemic encephalopathy: Pathophysiology and experimental treatments. Newborn Infant Nurs Rev. 2011;11:125–33.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Forni LG, Hodgson LE, Selby NM. The janus faces of bicarbonate therapy in the ICU: not sure. Intensive Care Med. 2020;46:522–4.

    Article  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. Ros J, Pecinska N, Alessandri B, Landolt H, Fillenz M. Lactate reduces glutamate-induced neurotoxicity in rat cortex. J Neurosci. 2001;66:790–4.

    CAS  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. Gupta BD, Sharma P, Bagla J, Parakh M, Soni JP. Renal failure in asphyxiated neonates. Indian Pediatrics. 2005;42:928–34.

    CAS  PubMed  Google Scholar 

  25. Rhee CJ, da Costa CS, Austin T, Brady KM, Czosnyka M, Lee JK. Neonatal cerebrovascular autoregulation. Pediatr Res. 2018;84:602–10.

    Article  PubMed  PubMed Central  Google Scholar 

  26. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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.

    Article  PubMed  Google Scholar 

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Authors and Affiliations



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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Correspondence to Eric S. Peeples.

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The authors declare no competing interests.

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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).

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