February 16, 2001

Severe neurological impairment in an infant after nitrous oxide anesthesia

McNeely JK, Buczulinski B, Rosner DR.
Anesthesiology 2000; 93 1549-50

Commentary by Charles Coté, M.D.

Return to the Current Literature Review

see abstract below

In the December 2000 issue of Anesthesiology, McNeely and colleagues reported an infant who developed severe neurologic impairment following an apparently uneventful nitrous oxide anesthetic for correction of craniosynostosis [1]. This impairment first developed several weeks after the anesthetic and during evaluation the child was discovered to be deficient in vitamin B₁₂. Apparently "nitrous oxide irreversibly oxidizes the cobalt atom of vitamin B₁₂ such that the activity of two vitamin B₁₂ -dependent enzymes, methionine synthetase and thymidylate synthetase, are decreased [2,3]." It is the methionine synthetase enzyme that converts homocysteine to methionine. Methionine is necessary for maintenance of the myelin sheath. The mother of the infant, who was breast feeding her baby, was vegetarian, and took no vitamin supplements. She also was borderline vitamin B₁₂ deficient. The authors concluded that "nitrous oxide should be avoided in an infant with unexplained neurologic impairment until vitamin B₁₂ deficiency can be ruled out."

This is a very interesting case report which has important implications, i.e. should we avoid the use of nitrous oxide in all patients at risk for vitamin B₁₂ deficiency? Over the years there have been a number of case reports of myeloneuropathy associated with the use of nitrous oxide in patients with vitamin B-12 deficiency [4-10] as well as case reports of neurologic degeneration with chronic exposure to nitrous oxide or abuse of nitrous oxide [11,12]. It is known that many populations are deficient in vitamin B₁₂, e.g. alcoholics, the elderly [13] vegetarians [14,15] adult patients and their breast-fed infants in less advantaged countries with poor dietary intake [16.17]. Avoiding the use of nitrous oxide in these populations would avoid the issue of enzyme inhibition and the potential for patient harm but it may deprive the patient of the benefits of nitrous oxide, i.e., less exposure to potent inhalation agents and analgesia. In some countries this may limit anesthesia to ketamine only. Although the case report suggests a cause and effect relationship between the vitamin deficiency and the subsequent neurologic demise of the patient, definitive proof is still lacking. This theoretic concern is just that--theoretical. Since nitrous oxide has been used for so many years in many hundreds of millions of patients from countries around the world with considerable variability in nutritional status it would seem likely that if such a cause and effect relationship was a real threat to patient safety that this would have been reported with a high frequency long before now. Certainly my knowledge of this area of medicine is very limited but common sense suggests that if, as the report suggests, there really is a cause and effect relationship, then there must also be another co-factor that causes the syndrome develop in a small number of patients but not in the vast majority–that is, the tens of millions of exposed patients at risk for B₁₂ deficiency. Until further information is developed, I see no reason to change current anesthetic practice.

References

1. McNeely JK, Buczulinski B, Rosner DR: Severe neurological impairment in an infant after nitrous oxide anesthesia.[In Process Citation].Anesthesiology 2000; 93: 1549-50
   
   
2. Guttormsen AB, Refsum H, Ueland PM: The interaction between nitrous oxide and cobalamin. Biochemical effects and clinical consequences. Acta Anaesthesiol Scand. 1994; 38: 753-6
   
   
3. Drummond JT, Matthews RG: Nitrous oxide inactivation of cobalamin-dependent methionine synthase from Escherichia coli: characterization of the damage to the enzyme and prosthetic group. Biochemistry 1994; 33: 3742-50. Link to abstract
   
   
4. Kinsella LJ, Green R: Anesthesia paresthetica': nitrous oxide-induced cobalamin deficiency. Neurology 1995; 45: 1608-10. Link to abstract
   
   
5. Flippo TS, Holder WD, Jr.: Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency. Arch Surg 1993; 128: 1391-5. Link to abstract
   
   
6. Sesso RM, Iunes Y, Melo AC: Myeloneuropathy following nitrous oxide anesthaesia in a patient with macrocytic anaemia. Neuroradiology 1999; 41: 588-90. Link to abstract
   
   
7. Marie RM, Le Biez E, Busson P, Schaeffer S, Boiteau L, Dupuy B, Viader F: Nitrous oxide anesthesia-associated myelopathy. Arch Neurol. 2000; 57: 380-2. Link to abstract
   
   
8. Rosener M, Dichgans J: Severe combined degeneration of the spinal cord after nitrous oxide anaesthesia in a vegetarian [letter]. J Neurol Neurosurg Psychiatry 1996; 60: 354.
   
   
9. Hadzic A, Glab K, Sanborn KV, Thys DM: Severe neurologic deficit after nitrous oxide anesthesia. Anesthesiology 1995; 83: 863-6
   
   
10. Holloway KL, Alberico AM: Postoperative myeloneuropathy: a preventable complication in patients with B12 deficiency. J Neurosurg. 1990; 72: 732-6. Link to abstract
    
    
11. Pema PJ, Horak HA, Wyatt RH: Myelopathy caused by nitrous oxide toxicity [see comments]. Am J Neuroradiol. 1998; 19: 894-6. Link to abstract
    
    
12. Layzer RB: Myeloneuropathy after prolonged exposure to nitrous oxide. Lancet 1978; 2: 1227-30. Link to abstract
    
    
13. Allen LH, Casterline J: Vitamin B-12 deficiency in elderly individuals: diagnosis and requirements [comment]. Am J Clin Nutr. 1994; 60: 12-4
    
    
14. Millet P, Guilland JC, Fuchs F, Klepping J: Nutrient intake and vitamin status of healthy French vegetarians and nonvegetarians. Am J Clin Nutr. 1989; 50: 718-27. Link to abstract
    
    
15. Helman AD, Darnton-Hill I: Vitamin and iron status in new vegetarians. Am J Clin Nutr. 1987; 45: 785-9. Link to abstract
    
    
16. Casterline JE, Allen LH, Ruel MT: Vitamin B-12 deficiency is very prevalent in lactating Guatemalan women and their infants at three months postpartum. J Nutr 1997; 127: 1966-72. Link to abstract
    
    
17. Allen LH, Rosado JL, Casterline JE, Martinez H, Lopez P, Munoz E, Black AK: Vitamin B-12 deficiency and malabsorption are highly prevalent in rural Mexican communities. Am J Clin Nutr. 1995; 62: 1013-9. Link to abstract

ABSTRACT

Severe neurological impairment in an infant after nitrous oxide anesthesia

AUTHORS:
McNeely JK, Buczulinski B, Rosner DR.

SOURCE:
Anesthesiology 2000; 93: 1549-50

ABSTRACT:
No abstract available.