Neurologic Degeneration Associated With Nitrous Oxide Anesthesia in Patients With Vitamin B12 Deficiency

Abstract

Vitamin B12 (cyanocobalamin) is an integral component of two biochemical reactions in man: the conversion of L-methylmalonyl coenzyme A into succinyl coenzyme A and the formation of methionine by methylation of homocysteine. The transmethylation reaction is essential to DNA synthesis and to the maintenance of the myelin sheath by the methylation of myelin basic protein. Active vitamin B12 contains cobalt in its reduced form (Co+). Nitrous oxide produces irreversible oxidation to the Co++ and Co forms that renders vitamin B12 inactive. Five cases (four from the literature and one new case) are presented in which patients unsuspected of having vitamin B12 deficiency developed subacute combined degeneration of the spinal cord following nitrous oxide anesthesia. Patients with vitamin B12 deficiency are exceedingly sensitive to neurologic deterioration following nitrous oxide anesthesia. If unrecognized, the neurologic deterioration becomes irreversible and may result in death.

Biological methylation of myelin basic protein: Enzymology and biological significance

“…When the experimental diet was supplemented with methionine, however, the animals were free of any detectable clinical changes (Scott e/ (I/., 1981). Crang and Jacobson (1980) and Flippo and Holder (1993) further demonstrated that a neurological syndrome similar to vitamin B,, deficiency can be produced in mice by injecting cycloleucine. Cycloleucine is an analogue of methionine that inhibits the biosynthesis of AdoMet.…”

Acupuncture for analgesia in the emergency department: a multicentre, randomised, equivalence and non‐inferiority trial

“…Patients deficient in vitamin B12, including those with a subclinical deficiency (ie without an associated anaemia), may develop a severe and progressive myeloneuropathy even after brief exposure to N 2 O. There are many examples of such case reports (Schilling, 1986;Holloway & Alberico, 1990;Flippo & Holder, 1993;Kinsella & Green, 1995;Nestor & Stark, 1996;Rosener & Dichgans, 1996;Sesso et al, 1999;Marie et al, 2000;Waters et al, 2005;Cartner et al, 2007;Wu et al, 2007;Meyers & Judge, 2008;Singer et al, 2008;Somyreddy & Kothari, 2008). Those at risk of vitamin B12 deficiency include some vegetarians (in particular vegans), the newborn of vegetarian mothers, patients with GI pathology, elderly people or patients taking PPIs and H2 blockers, and alcoholics (Schilling, 1986;Rosener & Dichgans, 1996;Nilsson-Ehle, 1998;Schenk et al, 1999;Carmel, 2000;McNeely et al, 2000;Sanders et al, 2008).…”

Unrecognized cobalamin deficiency, nitrous oxide, and reversible subacute combined degeneration

“…4 N 2 O accelerates the development of cobalamin deficiency symptoms by irreversibly inactivating cobalamin, and by decreasing methionine synthetase activity directly. 5 Previous reports suggest that the symptoms of early subacute combined degeneration following N 2 O exposure may be reversible with repletion of vitamin B 12 . 5,6 Recovery to independent ambulation has been reported in as few as 4 weeks with cobalamin therapy, with near-complete symptom resolution thereafter, 5 and with imaging improvement on MRI.…”

“…5 Previous reports suggest that the symptoms of early subacute combined degeneration following N 2 O exposure may be reversible with repletion of vitamin B 12 . 5,6 Recovery to independent ambulation has been reported in as few as 4 weeks with cobalamin therapy, with near-complete symptom resolution thereafter, 5 and with imaging improvement on MRI. 7 This case highlights anemia and DVT as an uncommon pair of symptoms from cobalamin deficiency, the latter due to secondary hyperhomocysteinemia.…”