What are the anesthetic considerations and peri‑operative management for a patient with pyruvate dehydrogenase deficiency?

Anesthetic Management of Pyruvate Dehydrogenase Deficiency

Patients with pyruvate dehydrogenase (PDH) deficiency require meticulous perioperative glucose and lactate management, with no specific anesthetic agent contraindicated, but prolonged propofol infusions must be avoided and lactate-free dextrose-containing fluids should be used throughout the perioperative period. 1, 2

Preoperative Assessment and Optimization

Critical Clinical Evaluation

• Assess for airway abnormalities, as these patients frequently present with hypotonia and neuromuscular degeneration that may complicate airway management 2, 3
• Evaluate baseline neurological status, as neurodevelopmental delay is the most common clinical sign and progressive deterioration can occur perioperatively 3, 4
• Document pre-existing respiratory abnormalities, as patients with respiratory compromise are at significantly higher risk of postoperative respiratory failure and metabolic decompensation 1
• Measure baseline lactate and acid-base status, as lactic acidosis is the hallmark of PDH deficiency and will be exacerbated by surgical stress 2, 5, 3

Preoperative Fasting Management

• Minimize preoperative fasting time aggressively—schedule surgery as the first case of the day to prevent metabolic decompensation 1, 6
• Initiate intravenous 5% or 10% dextrose in 0.9% saline (lactate-free solution) during the fasting period to maintain normoglycemia and prevent excessive glycolytic oxidation that increases lactate levels 1, 6
• Monitor capillary glucose hourly during fasting, targeting 70-180 mg/dL (3.9-10 mmol/L) 6, 7

Intraoperative Management

Fluid and Metabolic Management

• Use exclusively lactate-free intravenous fluids (5% dextrose in 0.9% saline) throughout the perioperative period, as lactated Ringer's will worsen lactic acidosis 1
• Maintain continuous glucose infusion at sufficient rates to keep blood glucose ≥70 mg/dL, as hypoglycemia triggers increased glycolysis and lactate production 1, 6, 7
• Monitor capillary glucose every hour during surgery, with any unexplained distress considered hypoglycemia until proven otherwise 6, 7, 2
• Monitor lactate levels intraoperatively, as rising lactate indicates metabolic decompensation and may predict postoperative complications 2, 5

Anesthetic Agent Selection

• Both volatile anesthetics and total intravenous anesthesia are acceptable, as there is no evidence that any specific anesthetic agent is associated with better outcomes in mitochondrial disease patients 1, 7
• Avoid prolonged propofol infusions for maintenance anesthesia, as propofol infusion syndrome can cause mitochondrial dysfunction and lactic acidosis 1
• Use neuromuscular relaxants judiciously given the underlying hypotonia and neuromuscular degeneration in these patients 1, 3
• Regional anesthesia techniques are reasonable alternatives when appropriate for the surgical procedure 1

Critical Intraoperative Monitoring

• Maintain continuous monitoring of acid-base status and lactate levels, as surgical stress and inflammatory mediators can precipitate critical mitochondrial failure 1, 2
• Monitor for signs of metabolic decompensation including unexplained tachycardia, hypotension, or rising lactate 2, 5

Postoperative Management

Immediate Recovery Period

• Continue glucose infusion until the patient is fully conscious, alert, and can resume oral feeding with demonstrated ability to maintain normoglycemia 6, 7
• Monitor glucose and lactate levels frequently in the immediate postoperative period until metabolic stability is confirmed 6, 2
• Resume oral feeding as soon as possible with small frequent meals to minimize reliance on glycolysis 6

Respiratory Monitoring

• Patients with pre-existing respiratory abnormalities require intensive monitoring, as postoperative respiratory failure is a documented complication in mitochondrial disease patients, particularly those with Leigh syndrome features 1
• Be prepared for prolonged ventilatory support or home ventilation requirements in severely affected patients 2

High-Risk Features Requiring Extra Vigilance

• Patients presenting in the first year of life with higher baseline lactate levels and lower residual enzyme activity have significantly worse outcomes and higher mortality risk 3, 4
• Patients with structural brain abnormalities (ventriculomegaly, corpus callosum dysgenesis, Leigh syndrome findings) represent more severe disease and require heightened perioperative monitoring 3, 4
• The surgical stress response with elevated inflammatory mediators can precipitate critical mitochondrial failure in the central nervous system, leading to clinical deterioration unrelated to anesthetic choice 1

Common Pitfalls to Avoid

• Using lactated Ringer's solution will directly worsen lactic acidosis—always use lactate-free crystalloids 1
• Prolonged fasting without glucose supplementation triggers metabolic crisis through increased glycolysis and lactate production 1
• Failing to monitor lactate levels intraoperatively may miss early signs of metabolic decompensation 2
• Underestimating the risk of postoperative respiratory failure, particularly in patients with documented respiratory abnormalities or severe neurological involvement 1, 2