Effects of Inhaled Anesthetics on Pulmonary Vasculature in Humans

One obvious explanation for differences in results between in vitro and in vivo studies is the influence of cardiac output. The direct effects of anesthetics on HPV compared with indirect actions mediated through changes in cardiac output were evaluated using data from several studies.^[193] The efficacy of HPV varies inversely with cardiac output (i.e., pulmonary arterial blood flow), and a direct inhibition of HPV by anesthetics may be opposed by a reduction in cardiac output such that HPV may appear to be unaffected. The net HPV response to volatile agents may be unchanged when the cardiac output is reduced, but it may be fully intact or minimally attenuated when cardiac output is maintained (e.g., during administration of nitrous oxide). These data emphasize the flow dependence of HPV in the presence of an inhaled anesthetic.

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Isoflurane does not alter pulmonary shunt function in healthy patients even at concentrations that produce systemic hypotension.^[194] The effects of diethyl ether and halothane on pulmonary blood flow distribution during nitrogen ventilation of one lung were examined in humans.^[185] HPV occurred in the nitrogen-ventilated lung during intravenous anesthesia with barbiturates but disappeared with the inhalation of halothane or diethyl ether in the ventilated lung. Abolition of HPV was accompanied in most patients by a decrease in arterial oxygenation. In contrast to the findings of this study, observations in experimental animals or in patients undergoing single-lung ventilation failed to demonstrate clinically significant attenuation of HPV during administration of halothane or desflurane.^[195] Isoflurane, sevoflurane, and desflurane have been shown to impair oxygenation more than intravenous infusions of propofol during single-lung ventilation in pigs and humans.^{[196] [197]} However, the differences in oxygenation observed in these studies are small and may be of little clinical relevance. These results differ from other findings demonstrating that shunt fraction is similar in patients receiving propofol or sevoflurane during single-lung ventilation.^[198] No significant differences in shunt fraction or arterial oxygen tension were observed when pulmonary gas exchange was compared during intravenous infusions of ketamine (which does not inhibit HPV) and administration of enflurane.^[199] Isoflurane and desflurane decreased shunt fraction and did not affect oxygenation during single-lung ventilation.^[200] Most clinical thoracic surgery is usually undertaken in the lateral position with an open chest, dramatically altering the relative distribution of ventilation and perfusion. Under these circumstances, a diseased, nondependent lung may substantially affect pulmonary vascular responsiveness to hypoxia, as may surgical manipulation of the lung itself. ^[201] These well-known observations limit applicability of studies evaluating the effects of inhaled anesthetics on shunt fraction and oxygenation conducted in animals or patients with normal lungs in the absence of surgical intervention.

Benumof and colleagues^[202] provided convincing evidence that inhaled anesthetics may be used safely in patients undergoing thoracotomy and single-lung ventilation. Halothane and isoflurane only minimally impair arterial oxygenation under these conditions ( Fig. 6-11 ). The increase in shunt and decrease in oxygenation caused by halothane or isoflurane in this study was consistent with an approximately 20% inhibition of HPV at 1 MAC. Instead of a reduction in pulmonary blood flow of 50% in a hypoxic lung in the absence of a volatile anesthetic, blood flow decreases by 40% during hypoxia in the presence of 1 MAC halothane or isoflurane. This change in flow corresponds to an increase in pulmonary shunt by about 4% of cardiac output.^[202] Similar and rather modest changes in shunt fraction and oxygenation were shown to occur with isoflurane, desflurane,^[203] and sevoflurane ^[204] in patients undergoing thoracotomy and single-lung ventilation. The use of total intravenous anesthesia with propofol and alfentanil did not decrease the risk of hypoxemia during single-lung ventilation.^[205] Isoflurane appears to be safe to use during single-lung ventilation, and administration of isoflurane before

Figure 6-11 Arterial oxygenation (PaO₂ ) and intrapulmonary shunt (Q_s /Q_t ) in patients ventilated with both lungs (2-LV) or with one lung (1-LV). Patients received an inhalational agent (IH) halothane or isoflurane followed by an intravenous anesthetic (IV) thiopental. Notice the minimal effect on PaO₂ and the shunt that occurs in changing from a volatile anesthetic to an IV agent. (Adapted from Benumof JL, Augustine SD, Gibbons JA: Halothane and isoflurane only slightly impair arterial oxygenation during one-lung ventilation in patients undergoing thoracotomy. Anesthesiology 67:910, 1987.)

Important factors that modulate the effects of HPV may also be baseline pulmonary artery blood flow and pressure. High pulmonary artery pressures may tend to cause passive distention of constricted vascular beds and thereby reverse HPV. Alternatively, reflex pulmonary and systemic vasoconstriction in response to hypotension may increase PVR in healthy lung segments, leading to a shift of blood flow to hypoxic areas of lung.

Remarkable increases in pulmonary shunting have been demonstrated by administration of pulmonary vasodilators (e.g., sodium nitroprusside, nitroglycerin) in dogs with oleic acid-induced pulmonary edema.^[135] Some volatile anesthetics may produce a similar response in patients with adult respiratory distress syndrome or with other types of pulmonary pathology associated

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The precise effects of inhaled anesthetics on HPV and pulmonary shunts in patients with preexisting pulmonary disease remain to be defined, but the action of these agents on the pulmonary vasculature itself must be considered when evaluating causes of hypoxemia during anesthesia. Additional investigations will be required in humans before the actions of inhaled anesthetics on these determinants of pulmonary function can be precisely predicted.

Clinical observations suggest that inhaled anesthetics exert only modest inhibitory effects on HPV and oxygenation. This relatively minor inhibition of HPV by inhaled anesthetics should not significantly influence clinical decision making, especially given the efficacy of nondependent lung continuous positive pressure in improving oxygenation. The net effect of anesthetics on HPV is multifactorial and depends on a number of other intraoperative factors that commonly occur during anesthesia and surgery.

Figure 6-12 Aspects of the reflex control of ventilation. Sensors include central and peripheral chemoreceptors as well as a variety of mechanoreceptors. Inputs from these many sources interact to alter ventilatory controller output from pontomedullary sites to muscles of respiration, altering ventilation and ultimately gas exchange.