Nitrous oxide consistently attenuates thermogenic and thermoperceptual responses to repetitive cold stress in humans.

Divers are at enhanced risk of hypothermia, due to the independent action of the inspired inert gases on thermoregulation. Thus, narcosis induced by acute (≤2 h) exposure to either hyperbaric nitrogen or normobaric nitrous oxide (N ₂ O) impairs shivering thermogenesis and accelerates body core cooling. Animal-based studies, however, have indicated that repeated and sustained N ₂ O administration may prevent N ₂ O-evoked hypometabolism. We, therefore, examined the effects of prolonged intermittent exposure to 30% N ₂ O on human thermoeffector plasticity in response to moderate cold. Fourteen men participated in two ∼12-h sessions, during which they performed sequentially three 120-min cold-water immersions (CWIs) in 20°C water, separated by 120-min rewarming. During CWIs, subjects were breathing either normal air or a normoxic gas mixture containing 30% N ₂ O. Rectal and skin temperatures, metabolic heat production (via indirect calorimetry), finger and forearm cutaneous vascular conductance (CVC; laser-Doppler fluxmetry/mean arterial pressure), and thermal sensation and comfort were monitored. N ₂ O aggravated the drop in rectal temperature ( P = 0.01), especially during the first (by ∼0.3°C) and third (by ∼0.4°C) CWIs. N ₂ O invariably blunted the cold-induced elevation of metabolic heat production by ∼22%-25% ( P < 0.001). During the initial ∼30 min of the first and second CWIs, N ₂ O attenuated the cold-induced drop in finger ( P ≤ 0.001), but not in forearm CVC. N ₂ O alleviated the sensation of coldness and thermal discomfort throughout ( P < 0.001). Thus, the present results demonstrate that, regardless of the cumulative duration of gas exposure, a subanesthetic dose of N ₂ O depresses human thermoregulatory functions and precipitates the development of hypothermia. NEW & NOTEWORTHY Human thermoeffector plasticity was evaluated in response to prolonged iterative exposure to 30% N ₂ O and moderate cold stress. Regardless of the duration of gas exposure, N ₂ O-induced narcosis impaired in a persistent manner shivering thermogenesis and thermoperception.