Journal: Br J Anaesth 99(6):812-818, 2007. 40 References
Reprint: Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Munster, Albert Schweizer Str. 33, 48129 Munster, Germany (JR Nofer, MD) RK.05 JU0820/170 ©2008
Faculty Disclosure: Abstracted by R. Klotz, who has nothing to disclose.
Nitrous oxide (N2O) is generally regarded as a safe anesthetic agent, but there is considerable evidence that intraoperative exposure to N2O causes adverse effects on the hematopoietic and nervous systems. Complications ranging from subtle hematologic changes to agranulocytosis, spinal cord degeneration, and polyneuropathy have been reported. Clinical symptoms after the exposure to N2O are highly reminiscent of those encountered in vitamin B12 (cobalamin) deficiency. Accordingly, adverse effects accompanying N2O anesthesia were aggravated in patients with subclinical cobalamin deficiency.
N2O acts by oxidizing vitamin B12 from the active cob(I)alamin to the inactive cob(III)alamin, which renders methylcobalamin, a metabolite of cobalamin, inactive as a cofactor of methionine synthase and impairs the conversion of homocysteine to methionine. Increased level of total homocysteine (tHcy) in serum is, therefore, an indicator of cobalamin deficiency and a biomarker of N2O exposure.
Healthcare workers in the operating room (OR) are repeatedly exposed to N2O in ambient air. Therefore, the authors investigated the biochemical indices of vitamin B12 metabolic status among surgical nurses working under various levels of exposure to N2O; 95 full-time OR nurses with a history of exposure and 90 unexposed counterparts were examined.
No apparent symptoms of acute N2O intoxication (headache, drowsiness, nausea and vomiting, paresthesia, and reduced tendon reflexes) were registered in an exposed group. All subjects denied receiving vitamin B12 or folic acid therapy during the 3 years preceding the study.
Nurses in both groups were examined once in the course of the study. Blood and air samples were collected on the same day. Blood was obtained simultaneously in both groups at the end of the daily shift. For determination of hematological parameters (RBC, HgB, Hct, MCH, MCV, and MCHC) EDTA-blood was collected and blood counts were tested within 2 hours. Vitamin B12 and folic acid were determined. No changes in vitamin B12 concentrations were observed in serum samples saturated with N2O excluding the direct interference of N2O with the immunoassay. Serum B12 concentrations (normal 156-672) were arbitrarily categorized as low (150-250), border low (250-300), medium (250-350), or high (>350). Values in the low category are encountered at increased frequency in subjects with disturbed vitamin B12 metabolism.
N2O and volatile anesthetics in the ambient air were evaluated in 26 ORs of 10 hospitals. Fifteen of the 26 ORs had provision for anesthetic gas scavenging devices. Anesthetic concentrations were measured continuously during consecutive surgeries carried out with anesthesia maintained with N2O and sevoflurane, isoflurane, or halothane. Each monitoring session was carried out for the duration of the anesthetic but not shorter than 75% of the shift, which allowed expression of the N2O air concentration in terms of occupational exposure limit.
No differences were observed in erythrocyte count, Hgb, Hct, MCH, MCV, and MCHC. In contrast, serum concentrations of vitamin B12 were significantly lower in exposed subjects. Monitoring of anesthetics in the ORs revealed that N2O most severely contributed to ambient air pollution. N2O levels measured in the respiratory area of nurses varied over three orders of magnitude and ranged from 35.8 to 1502 mg/mL depending on the ventilation system. In contrast, none of the ORs’ concentrations of volatile anesthetics, including isoflurane and halothane, exceeded values recommended.
In this study, the authors found significantly reduced vitamin B12 levels in surgical nurses when compared with hospital staff outside the OR. This observation was the first indication that repeated occupational exposure to N2O may disturb vitamin B12 metabolic status. Previous studies have demonstrated that the air pollution with N2O during surgical procedures is critically dependent on the waste scavenging systems in the ORs. Only combinations of exhaust ventilation or air conditioning with scavenging devices were revealed to reduce the level of N2O contamination. Only nurses working in the environment, in which occupational exposure limit values greater than 180, presented with decreased vitamin B12 and increased tHcy levels.
The authors conclude that the clinical relevance of the present results remains unclear. Maintaining N2O concentrations in ORs under occupational exposure limit is sufficient for preventing disturbances in vitamin B12 metabolism. Conversely, excessive repeated occupational exposure to N2O is associated with alterations of vitamin B12, the extent which is critically dependent on the level of exposure. |
