Can rewarming after therapeutic hypothermia in a newborn with Hypoxic-Ischemic Encephalopathy (HIE) cause lactic acidosis?

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Last updated: January 14, 2026View editorial policy

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Rewarming After Therapeutic Hypothermia and Lactic Acidosis Risk

Rewarming after therapeutic hypothermia does not directly cause lactic acidosis, but the metabolic derangements from the underlying hypoxic-ischemic injury persist during rewarming, and rapid rewarming may worsen metabolic instability. 1

Understanding the Metabolic Context

The relationship between rewarming and metabolic status is complex and relates more to the severity of the underlying brain injury than to the rewarming process itself:

  • Mitochondrial dysfunction from the initial hypoxic-ischemic injury persists during rewarming, particularly in infants with moderate-to-severe encephalopathy, as evidenced by impaired cerebral oxidative metabolism 2, 3

  • Infants with higher lactate/N-acetylaspartate ratios (indicating worse brain injury) show progressively impaired relationships between mitochondrial metabolism and oxygenation during rewarming, with correlation coefficients dropping from 0.41 in mild injury to 0.01 in severe injury 2

  • The metabolic derangement is a consequence of the hypoxic-ischemic injury itself, not the rewarming process 2, 3

Critical Rewarming Protocol to Minimize Complications

Rewarming must occur slowly over at least 4 hours at approximately 0.5°C per hour to prevent complications 4, 5:

  • The American Heart Association explicitly identifies rapid rewarming as a critical pitfall to avoid 4, 5

  • Cardiovascular parameters (heart rate, blood pressure, oxygen saturation) remain stable during properly conducted rewarming 2

  • The optimal rate of rewarming remains a knowledge gap, with current recommendations based on preventing hyperthermia and other complications rather than specific metabolic endpoints 1

Monitoring During Rewarming

Maintain physiological stability throughout the rewarming period 4:

  • Monitor and maintain adequate ventilation and oxygenation 4, 5
  • Target PaCO₂ of 4.5-5.0 kPa 4
  • Maintain systolic blood pressure >110 mmHg 4
  • Continue intravenous glucose infusion to avoid hypoglycemia 4, 5
  • Monitor for and treat complications including thrombocytopenia and need for inotropic support 5

Key Clinical Caveat

Future research is specifically needed on the effect of rewarming rate on metabolic markers such as acidosis, indicating this remains an area of uncertainty 1. However, the evidence suggests that any metabolic acidosis observed during rewarming reflects the severity of the underlying hypoxic-ischemic injury and impaired mitochondrial function rather than being caused by the rewarming process itself 2, 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Therapeutic Hypothermia in Hypoxic-Ischemic Encephalopathy (HIE)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Birth Asphyxia in NICU

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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