British Journal of Anaesthesia, Vol 76, Issue 5 652-656, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia
J. D. Young, J. W. Sear and E. M. Valvini
Inhaled nitric oxide is used increasingly to treat pulmonary hypertension
and ventilation/perfusion mismatching in seriously ill patients, but little
is known of the pharmacokinetics of its two principal metabolites,
methaemoglobin and nitrogen oxides (nitrates and nitrites). We have studied
the changes in these metabolites in six healthy volunteers during and after
3 h inhalation of 100 volumes per million of nitric oxide. Mean nitric
oxide uptake was 0.49 (SD 0.08) ml min-1 at standard temperature and
pressure, corresponding to 74% of the inhaled dose. During inhalation,
methaemoglobin increased monoexponentially with a time constant of 45.6
(11.1) min by 1.77 (0.47)% of total haemoglobin. Serum nitrogen oxides
increased from 36.7 (7.6) to 124 (17) mumol litre-1, with a time constant
of 172 (91.4) min and a volume of distribution of 331 (104) ml kg-1. The
volume of distribution for methaemoglobin calculated from nitric oxide
uptake and the increase in methaemoglobin, was, on average, 14.3% less than
predicted blood volume, suggesting that most of the absorbed nitric oxide
initially forms methaemoglobin. Serum nitrogen oxides declined initially
after inhalation ceased but then increased to a second peak between 45 and
180 min later. The cause of the second peak was not determined.
CLINICAL INVESTIGATIONS
Kinetics of methaemoglobin and serum nitrogen oxide production during inhalation of nitric oxide in volunteers
Nuffield Department of Anaesthetics, Radcliffe Infirmary, Woodstock Rd, Oxford OX2 6HE
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