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

Abstract

Divers are at enhanced risk of hypothermia, due to the independent action of the inspired inert gases on thermoregulation. Thus, narcosis induced by acute (≤2h) exposure to either hyperbaric nitrogen, or normobaric nitrous oxide (N2O) impairs shivering thermogenesis and accelerates body core cooling. Animal-based studies, however, have indicated that repeated and sustained N2O administration may prevent the N2O-evoked hypometabolism. We therefore examined the effects of prolonged intermittent exposure to 30% N2O 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 immersions (CWI) in 20˚C water, separated by 120-min rewarming. During CWIs, subjects were breathing either normal air, or a normoxic gas mixture containing 30% N2O. 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. N2O aggravated the drop in rectal temperature ( P = 0.01), especially during the first (by ~0.3°C) and third (by ~0.4°C) CWIs. N2O 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, N2O attenuated the cold-induced drop in finger ( P ≤ 0.001), but not in forearm CVC. N2O alleviated the sensation of coldness and thermal discomfort throughout ( P < 0.001). Thus, present results demonstrate that, regardless of the cumulative duration of gas exposure, a subanasthetic dose of N2O depresses human thermoregulatory functions, and precipitates the development of hypothermia.

Combined effects of mild hypothermia and nitrous-oxide-induced narcosis on manual and cognitive performance

“…In support of our hypothesis, N 2 O interfered with sensory, affective, and intellectual processes, compromising markedly all cognitive domains tested. N 2 O also suppressed autonomic thermoeffector function (i.e., shivering thermogenesis, as indicated by the blunted elevation in V̇ o 2 ), accelerating the rate of body core cooling; a finding that conforms to those from other works ( 34 – 37 ) and has been discussed extensively in our previous study ( 38 ). Considering that, in the present investigation, intersession differences in cognition were assessed by using an open-loop experimental approach (i.e., subjects’ thermal status remained unclamped), it may be reasoned that the augmented cognitive decline in N 2 O was dictated by the more prominent hypothermia obtained in this condition.…”

“…A subset of the temperature, thermoperceptual, and cardiorespiratory data have been presented and discussed previously (see Ref. 38 ); however, the data concerning the neurocognitive and psychomotor performance are novel.…”

“…An a priori power analysis was not performed for the specific data set, because the present work addressed a secondary purpose of the larger project (see Ref. 38 ). All subjects resided in the Stockholm region for ≥6 mo before the study, were physically active, were nonsmokers, and were not taking any prescription medications.…”

“…CWIs were separated by a 120-min rewarming period, during which subjects were inspiring room air, and their rectal temperature (T rec ) returned to the CWI A preimmersion values (see Ref. 38 ). In both test sessions, subjects reported to the laboratory at 07:00; CWI A , CWI B , and CWI C were performed at ∼8:30, 12:30, and 16:30 h, respectively.…”

“…Human-based studies have demonstrated that behavioral tolerance to N 2 O does not develop, given that its deleterious effects on cognition fail to subside over prolonged and/or repeated N 2 O administration ( 31 – 33 ). Notably, normobaric N 2 O, as well as hyperbaric N 2 , also perturbs autonomic and behavioral thermoregulation to cold; namely, shivering thermogenesis and thermoperception are suppressed consistently ( 34 – 38 ). However, to our knowledge, the manner in which inert gas narcosis interferes with cognitive processes during cold stress has as yet not been determined.…”