- Cobalamin/N2O related risks are actually smaller in participants than in nonparticipants. Several layers of protection against the small risks associated with the study include the cobalamin-related evaluation that is not otherwise done routinely before N2O anesthesia to identify patients who are at known risk from N2O; continued postoperative monitoring for changes in cobalamin status and significant cognitive decline; intervention with cobalamin therapy in possibly affected patients; institution of a Data Safety Monitoring plan with an independent safety monitor; and interim analysis of study findings.