Metabolic, ventilatory and circulatory effects of doxapram in anaesthetized pigs during normoxia and hypoxia

In a previous clinical study doxapram was found to improve ventilatory efficacy postoperatively, presumably via effects on hypoxic pulmonary vasoconstriction (HPV). The present study was designed to see whether doxapram induced any changes of arterial oxygenation and pulmonary vascular resistance during normoxia or hypoxia and whether the changes were influenced by the anaesthetic agents.

Seventeen piglets were anaesthetized by combinations of either midazolam + fentanyl + pancuronium + pentobarbital (TIVA, n = 9), or by midazolam + fentanyl + pancuronium + halothane, 0.5% in end-tidal gas (Hal, n = 8). Analyses of expired gas and mixed venous and arterial blood in combination with determinations of central blood flow and pressures allowed for calculations of standard metabolic, ventilatory and circulatory data. Values were obtained at normoventilation using normoxic (FIO2 = 0.3) and hypoxic (FIO2 = 0.08) gas mixtures at calculated doxapram plasma concentrations of 1, 2 and 4 micrograms.ml-1.

With few exceptions doxapram administration affected the investigated variables only moderately during normoxia. In group Hal, PVR and SVR showed a biphasic raise (P < 0.05), CO fell (P < 0.05-P > or = 0.05) and C (a-v)O2 rose (P < 0.05). In group TIVA, PaO2 fell (P < 0.01-0.05) despite unchanged PVR, CO and VD/VT. Hypoxia affected a moderate increase in PVR in group TIVA (P < 0.05), which was slightly lower at the lowest and highest plasma levels of doxapram (P < 0.05). In group Hal, the induction of hypoxia induced a more pronounced rise in PVR (P < 0.05) which showed a biphasic response to increasing dose levels of doxapram, the lowest dose affecting a further rise (P < 0.05) and the highest a reduction to values below hypoxia control levels (P < 0.05). Pronounced differences between the two groups with respect to values for metabolic and circulatory variables make the interpretation of data difficult.

Doxapram administration to anaesthetized animals did not induce any effects indicative of augmentation of the HPV response.