Ventilatory Responses to Acute Metabolic Acidemia in Humans Awake, Sedated, and Anesthetized with Halothane

Abstract

Acute metabolic acidemia was induced in human subjects awake, sedated with halothane (0.1 MAC [minimum alveolar concentration]), and anesthetized with halothane (1.0 MAC) by infusing L-arginine HCl, 5-6 mmol .cntdot. kg-1, over 3 h. Ventilation was recorded at resting arterial H ion concentration ([H+]a) and at 2-4 isocapnic increments of [H+]a, in each case, while end-tidal O2 tension (PETO2), was varied between > 300 mm Hg and 45 mm Hg. Total increments of [H+]a in awake, sedated and anesthetized subjects were 13 .+-. 4, 12 .+-. 2 and 12 .+-. 3 nmol .cntdot. l-1 (means .+-. SD). In the awake state, metabolic acidemia increased ventilation (.ovrhdot.VI) in proportion to [H+]a. The magnitude of response increased with reduced PETO2, such that the response to acidemia and hypoxemia combined was synergistic. The .DELTA..ovrhdot.VI/.DELTA.[H+]a slopes at PETO2 values of > 300, 100-120, and 45 mm Hg were 0.47 .+-. 0.27, 0.85 .+-. 0.24, and 3.01 .+-. 1.30 l .cntdot. min-1 .cntdot. nmol-1 .cntdot. l, respectively (means .+-. SD). Halothane sedation reduced the responses to added [H+]a determined at PETO2 values of 100-120 and 45 mm Hg, as well as the response to hypoxemia and to the interaction of acidemia and hypoxemia, each to less than half awake values. Halothane anesthesia further impaired the responses to [H+]a and virtually abolished the response to hypoxemia and to acidemia-hypoxemia interaction. A small residual response to added [H+]a during anesthesia could be accounted for by a slight concurrent increase of PaCO2 [arterial CO2 partial pressure] leaving no response attributable to metabolic [H+]a itself. The lack of ventilatory response to metabolic [H+] during anesthesia, when a response to CO2 was clearly present, suggests that the metabolic acid stimulus did not reach the medullary chemoreceptors. Halothane in humans markedly reduces the peripheral chemoreceptor-mediated responses to metabolic acidemia and to acidemia-hypoxemia interaction, in parallel with its previously described effect on the response to hypoxemia. During light halothane anesthesia, ventilation is virtually unaffected by either the acidity or the O2 tension of the blood.