What are the anaesthetic implications for patients with Phenylketonuria (PKU)?

Anaesthetic Implications of Phenylketonuria (PKU)

Patients with phenylketonuria (PKU) require careful perioperative management with special attention to metabolic control, as elevated phenylalanine levels can directly impact neurological function and mood, potentially complicating anesthetic management and recovery.

Understanding PKU and Its Metabolic Control

PKU is an autosomal recessive disorder characterized by deficiency or absence of phenylalanine hydroxylase enzyme activity, leading to elevated phenylalanine (Phe) levels in blood and tissues 1. If untreated, PKU results in intellectual disability, microcephaly, seizures, and behavioral abnormalities.

The cornerstone of PKU management is strict metabolic control through:

• Phenylalanine-restricted diet
• Supplementation with Phe-free formula containing tyrosine
• Regular monitoring of plasma Phe levels

Target Phe levels according to NIH consensus panel 1:

• Children up to 12 years: 2-6 mg/dL (120-365 μmol/L)
• Individuals older than 12 years: 2-15 mg/dL (120-910 μmol/L)
• Pregnant women: 2-6 mg/dL (120-365 μmol/L)

Pre-Anesthetic Assessment

1. Metabolic Status Assessment:

   • Review recent Phe levels (ideally within 1 week of surgery)
   • Assess current dietary compliance
   • Check for signs of poor metabolic control (cognitive issues, mood disturbances)

2. Neurological Evaluation:

   • Assess for cognitive impairment, which may affect perioperative communication
   • Screen for attention deficits and executive function issues 2
   • Evaluate for anxiety/depression which may be exacerbated by high Phe levels 2

3. Nutritional Status:

   • Check for micronutrient deficiencies (especially vitamin B12 and vitamin D) 3
   • Review current protein intake and supplementation

Perioperative Management

Preoperative Period

1. Maintain Metabolic Control:

   • Continue Phe-restricted diet until NPO period
   • Consider measuring Phe levels preoperatively if recent values unavailable
   • Coordinate with metabolic specialist for patients with poor control

2. Medication Considerations:

   • Review all medications for protein/aspartame content
   • Avoid medications containing aspartame (source of phenylalanine)
   • Consider potential drug interactions with any PKU medications (e.g., sapropterin, pegvaliase) 1

Intraoperative Management

1. IV Fluid Selection:

   • Use Phe-free IV solutions
   • Avoid protein-containing solutions in prolonged procedures
   • Consider dextrose-containing solutions to prevent catabolism

2. Anesthetic Technique:

   • No specific contraindications to general or regional anesthesia
   • Monitor for potential exaggerated responses to sedatives in patients with neurological involvement
   • Consider potential for increased anxiety due to high Phe levels 2

3. Metabolic Monitoring:

   • For prolonged procedures, consider monitoring blood glucose to prevent catabolism
   • Maintain normothermia to prevent increased metabolic demands

Postoperative Care

1. Early Resumption of Diet:

   • Resume Phe-restricted diet as soon as possible
   • Provide Phe-free formula/supplements when oral intake is permitted
   • Coordinate with dietitian for appropriate nutritional support

2. Monitoring:

   • Consider checking Phe levels after prolonged procedures or in patients with poor preoperative control
   • Monitor for neurological changes that could indicate metabolic decompensation
   • Assess for adequate pain control, as stress can increase catabolism

3. Medication Management:

   • Continue to avoid aspartame-containing medications
   • Resume PKU-specific medications as soon as clinically appropriate

Special Considerations

Pregnancy

For pregnant women with PKU, maintaining strict Phe control is critical 1:

• Target Phe levels: 2-6 mg/dL during pregnancy
• Poor control during pregnancy can lead to fetal complications including microcephaly, congenital heart disease, and developmental delays
• Coordinate closely with metabolic specialist and obstetrician

Emergency Surgery

In emergency situations:

• Obtain baseline Phe level if possible
• Proceed with surgery without delay
• Consult metabolic specialist as soon as possible
• Resume dietary management at earliest opportunity

Pediatric Patients

Children with PKU require special attention:

• More stringent Phe control targets (2-6 mg/dL)
• May have more pronounced neurological effects from metabolic decompensation
• Parents/caregivers should be involved in perioperative planning

Potential Complications

1. Neuropsychiatric Effects:

   • Elevated Phe levels directly impair sustained attention and mood 2
   • May affect patient cooperation and recovery
   • Can complicate postoperative pain management and rehabilitation

2. Nutritional Deficiencies:

   • Long-term dietary restrictions may lead to micronutrient deficiencies
   • May affect wound healing and recovery

3. Stress Response:

   • Surgical stress may increase protein catabolism
   • Can lead to increased Phe levels postoperatively

Conclusion

The key to successful anesthetic management of PKU patients lies in maintaining metabolic control throughout the perioperative period. Close coordination with the patient's metabolic specialist, early resumption of dietary therapy, and careful medication selection are essential components of care.