Effects of subanesthetic dose of nitrous oxide on cerebral blood flow and metabolism: A multimodal magnetic resonance imaging study in healthy volunteers

Background: Nitrous oxide, in a concentration of 50% or more, is a known cerebral vasodilator. This study investigated whether a lower dose (30%) of nitrous oxide would also increase cerebral blood flow. In addition, the authors wished to study whether the increase in cerebral blood flow was accompanied by an increase in cerebral metabolism. Methods: Multimodal Magnetic Resonance Imaging at 3T was performed, and data were obtained in 17 healthy volunteers during three inhalation conditions: medical air, oxygen-enriched medical air (40% oxygen), and 30% nitrous oxide with oxygen-enriched medical air (40% oxygen). Arterial spin labeling was used to derive the primary tissue specific hemodynamic outcomes: cerebral blood flow, arterial blood volume and arterial transit times. Magnetic Resonance Susceptometry and proton Magnetic Resonance Spectroscopy were used for secondary metabolic outcomes: venous oxygenation, oxygen extraction fraction, cerebral metabolic oxygen rate and prefrontal metabolites. Results: Nitrous oxide in 40% oxygen, but not 40% oxygen alone, significantly increased gray matter cerebral blood flow (22%; P <0.05) and arterial blood volume (41%; P <0.05). Venous oxygenation increased in both oxygen and nitrous oxide conditions. Compared with medical air inhalation, nitrous oxide condition caused a significantly larger decrease in oxygen extraction fraction than 40% oxygen alone (mean [SD] 11.3 [5.6]% vs. 8.3 [5.9]% P <0.05), while global cerebral metabolic rate and prefrontal metabolites remained unchanged. Conclusions: This study demonstrates that 30% nitrous oxide in oxygen-enriched air (40% oxygen) significantly increases cerebral perfusion, and reduces oxygen extraction fraction, reflecting a strong arterial vasodilatory effect without associated increases in metabolism.