Systemic and hepatic O2 deliveries decreased with increasing concentrations of desflurane (Figure 2; Table 1). In contrast to the dose-dependent reductions in whole-body and hepatic O2 supply, small intestinal O2 delivery decreased at 0.5 MAC but did not show any further reduction at 1.0 MAC (Figure 2). The dose-dependent decrease in hepatic O2 delivery was not only due to a decrease in blood flow but also the result of a decrease in portal venous O2 saturation (Table 1). Oxygen uptake of whole body, liver, and small intestine did not change significantly. However, systemic and small intestinal O2 extraction ratios increased in a dose-dependent fashion (Table 1). Hepatic O2 extraction ratio remained unchanged at 0.5 MAC but increased at the higher concentration. The respective changes in hepatic and small intestinal O2 deliveries and extraction ratios resulted in dose-dependent reductions in superior mesenteric and hepatic venous O2 saturations.
Desflurane produced a dose-dependent decrease in mean liver surface PO (2) and a leftward shift of summary surface PO2 histograms of the liver (Figure 3). However, there were no PO2 values in the hypoxic range (0-10 mm Hg). Mean small intestinal surface PO2 remained unchanged at 0.5 MAC but decreased at 1.0 MAC. Summary surface PO2 histograms of the intestinal serosa broadened at both concentrations of desflurane.
As shown in Table 1, there was no change in hepatic lactate uptake and intestinal lactate production at either desflurane concentration. Ketone-body ratio in arterial blood did not change throughout the entire experiment (Table 1). The plasma activity of ALT and AST remained within normal limits at both concentrations of desflurane.
Hemoglobin concentration and body temperature remained unchanged (Table 1). In the three control animals, differences between baseline values and those obtained 1 and 2 h thereafter did not exceed 10%.
The principal findings of this study are as follow: 1) Hepatic arterial blood flow was maintained at 0.5 MAC of desflurane, whereas portal venous, total hepatic, and superior mesenteric arterial blood flows decreased at this concentration. All splanchnic blood flows decreased at 1.0 MAC of desflurane. 2) Oxygen delivery of whole body, liver, and small intestine was markedly reduced at both concentrations. However, the uptake of total systemic, liver, and small intestinal O2 did not change significantly. The decreases in hepatic and small intestinal O2 deliveries were reflected by changes in surface PO2. 3) Desflurane had no adverse effects on indicators of hepatic and small intestinal metabolic function.
We studied young pigs because the MAC of desflurane for pigs had previously been determined in a study with animals three to four months of age and weighing 14 to 22 kg . The investigated pigs (aged four to five months) have to be considered adolescent since they reach sexual maturity at the age of nine months. One has to take into account that anesthetic requirements for desflurane decreases progressively with increasing age. The results do therefore not necessarily apply to human adults.
Laparotomy and mechanical ventilation are both known to interfere with splanchnic perfusion [2,16,17]. Ketamine  and vecuronium  have no or little effect on hepatic and preportal circulation. The effects of flunitrazepam on the splanchnic circulation are unknown. It must be emphasized that the effects observed during desflurane occurred during baseline anesthesia and surgery. Both baseline anesthesia and surgery may have resulted in spontaneous deterioration of the preparation over time. However, data obtained in control animals during baseline conditions exclude such deterioration. The effect of desflurane was studied under baseline anesthesia in order to mimic the clinical condition of balanced anesthesia where a volatile anesthetic is added to deepen anesthesia. In addition, this experimental design allows comparison of these results with those of isoflurane anesthesia in the same experimental model . Both concentrations of desflurane were administered in random order to exclude modifying effects of the experimental procedure.
The technique of measuring surface PO2 using oxygen-sensitive multiwire electrodes is well established and discussed in previous studies [3,6,10,11]. Although surface PO2 may not reflect whole organ PO2, this technique allows determination of tissue PO2 without tissue damage and interference with the microcirculation [6,11].
The desflurane-induced dose-dependent decreases in mean arterial blood pressure and cardiac output are comparable to those found during isoflurane and enflurane anesthesia in the same pig model . In chronically instrumented pigs  and two studies with chronically instrumented dogs [5,9], mean arterial pressure decreased similarly, but in contrast to our findings, heart rate increased. Cardiac output decreased in a similar fashion but only at higher concentrations of desflurane . The difference in findings may be explained by the baseline anesthesia our animals received which might have blunted the sympathetic response to desflurane. Pretreatment of volunteers or dogs with drugs that block sympathetic activity attenuated the increase in heart rate observed during induction of anesthesia with desflurane [20,21]. In another study, a sustained increase in circulating catecholamines in patients was found after a rapid increase of the inspired concentration of desflurane . Therefore, we aimed at avoiding sympathetic stimulation by increasing the end-tidal concentration of desflurane gradually over 20 minutes. Since desflurane causes only transient sympathetic stimulation, we allowed an additional period of 30 minutes for hemodynamic stabilization after reaching stable end-tidal concentrations of desflurane. The increase in cardiac filling pressures at 1.0 MAC and a simultaneous decrease in cardiac output is consistent with previously reported negative inotropic effects of desflurane [19,22]. Whereas portal venous, superior mesenteric arterial, and total hepatic blood flows decreased at 0.5 MAC, hepatic arterial blood flow remained unchanged, and decreased only at the higher concentration of desflurane. In chronically instrumented dogs, hepatic arterial blood flow remained unchanged up to 2.0 MAC of desflurane, but portal venous blood flow decreased at 1.75 MAC, resulting in a significant decrease in total hepatic blood flow . The latter finding is consistent with our study but was observed at higher concentrations of desflurane. The difference in concentrations of desflurane might be explained by the fact that the dogs had no baseline anesthesia. Using the microsphere technique in chronically instrumented dogs , hepatic blood flow remained unchanged even at desflurane concentrations which produced similar changes in mean arterial pressure as in the present study. This difference in results might be attributed to a different response in cardiac output. In chronically instrumented dogs, decreases in mean arterial pressure were accompanied by increases in heart rate. Cardiac output was not measured. Due to the increase in heart rate, cardiac output might not have decreased to the same extent as in our study so that liver perfusion could be maintained. A direct comparison between the results is difficult because models differ in species (dog versus pig), state of consciousness (awake versus anesthetized and mechanically ventilated), preparation (chronically instrumented versus acutely operated), and technique of blood flow measurement (radioactive microspheres versus flow transducers).
Desflurane at 0.5 MAC caused a marked decrease in hepatic arterial vascular resistance in the presence of unchanged systemic and small intestinal vascular resistances. The selective vasodilation of the hepatic arterial vascular bed at 0.5 MAC might have been caused by the "hepatic arterial buffer response," which controls hepatic perfusion so that changes in portal blood flow lead to compensatory changes in hepatic arterial blood flow . The finding that a decrease in portal blood flow was paralleled by hepatic arterial vasodilation suggests that the hepatic arterial buffer response mechanism was, at least in part, responsible for the decrease in hepatic arterial resistance at 0.5 MAC. This possibility is further supported by the observation that both portal flow and hepatic arterial resistance remained constant between 0.5 and 1.0 MAC of desflurane.
Unchanged arterial O2 saturation would suggest that the reduction in O2 delivery of whole body and small intestine was the result of the decrease in blood flow. The decrease in superior mesenteric venous and, subsequently portal venous O2 saturation was caused by an increase in small intestinal O2 extraction. Despite preserved hepatic arterial O2 delivery at 0.5 MAC of desflurane, total hepatic O2 delivery decreased in a dose-dependent manner due to the decrease in portal venous O2 delivery. This, in turn, was the result of a reduction in portal blood flow and O2 saturation. These findings are similar to those produced by other volatile anesthetics in the same  as well as in other experimental models . Despite diminished O2 delivery, O2 uptake by liver and small intestine remained unchanged at both desflurane concentrations, suggesting that a critical level of O2 delivery at which O2 uptake becomes supply-dependent had not yet been reached. Supply dependency of O2 uptake would reflect a condition of inadequate O2 supply and therefore a dysoxic state .
The decrease in hepatic and small intestinal O2 deliveries during desflurane was accompanied by a reduction in mean surface PO2 and a leftward shift of liver surface PO2 histograms at both concentrations. Small intestinal surface PO2 histograms were merely broadened at 0.5 MAC of desflurane, and shifted to regions of lower PO2 values at the higher concentration of desflurane. Such changes in surface PO2 histograms are the result of reduced convective O2 transport, but are unlikely to reflect tissue hypoxia or severe disturbance at the microcirculation level, because no hypoxic PO2 values (below 5 mm Hg) were observed, and no histogram assumed an irregular shape . Surface PO2 histograms are comparable to those observed during isoflurane and enflurane anesthesia .
Despite significant decreases in hepatic and small intestinal O2 deliveries during increasing desflurane concentrations, there were no changes in hepatic lactate uptake, intestinal lactate release, or systemic arterial ketone-body ratio (beta-OH-butyrate/acetoacetate). Since hepatic lactate uptake reflects the state of hepatic oxygenation [24-26], and the ketone-body ratio that of the hepatic mitochondrial redox state , these findings suggest that desflurane has no adverse effects on hepatic intermediary metabolism.
The plasma activities of ALT and AST remained unchanged, indicating preserved hepatocellular integrity. These findings are consistent with those of other investigators [4,27].
In conclusion, in the presence of baseline anesthesia and surgical stress, desflurane caused reductions in hepatic and small intestinal blood flow and O2 supplies in parallel with decreases in cardiac output and mean arterial pressure. The concomitant decreases in hepatic and small intestinal O2 deliveries reduced surface tissue oxygenation. However, there was no evidence of severe tissue hypoxia or disturbed oxygen-dependent intermediary metabolism. It has to be realized that the effects of desflurane occurred at a level of hypotension usually avoided in the clinical setting. Nevertheless, it is possible that desflurane-induced hypotension may carry some risks in patients with compromised splanchnic perfusion and oxygenation.
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© 1997 International Anesthesia Research Society
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