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GENERAL ARTICLES

The Effects of Increasing Concentrations of Desflurane on Systemic Oxygenation During One-Lung Ventilation in Pigs

Waheedullah Karzai, MD^*, Jörg Haberstroh, VMD, and Hans-Joachim Priebe, MD^*

Departments of *Anesthesia and Surgical Research, University Hospital Freiburg, Freiburg, Germany

Address correspondence and reprint requests to W. Karzai, MD, Department of Anesthesia, University Hospital, 07740 Jena, Germany. Address e-mail to karzai{at}anae1.med.uni-jena.de

	Abstract

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During one-lung ventilation (OLV), hypoxic pulmonary vasoconstriction reduces venous admixture and attenuates the decrease in arterial O₂ tension by diverting blood from the nonventilated to the ventilated lung. In vitro, increasing concentrations of desflurane depresses hypoxic pulmonary vasoconstriction in a dose-dependent manner. Accordingly, we investigated the effects of increasing concentrations of desflurane on oxygenation during OLV in vivo. Thirteen pigs (25–30 kg) were anesthetized (induction: propofol 2–3 mg/kg IV;maintenance: N₂O/O₂ 50%/50%, desflurane 3%, propofol 50 µg · kg^-1 · min^-1, and vecuronium 0.2 mg · kg^-1 · h^-1 IV), orotracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided, 28F, double-lumen tube was placed via tracheotomy. After double-lumen tube placement, N₂O and desflurane were discontinued, propofol was increased to 200 µg · kg^-1 · min^-1, and the fraction of inspired oxygen was adjusted at 0.8. Anesthesia was then continued in random order with desflurane 5%, 10%, or 15% end-tidal concentrations while propofol was discontinued. Whereas mixed venous PO₂, mean arterial pressure, cardiac output, and shunt fraction decreased in a dose-dependent manner, PaO₂ remained unchanged with increasing concentrations of desflurane during OLV. These findings indicate that, in vivo, increasing concentrations of desflurane do not necessarily worsen oxygenation during OLV.

Implications: Oxygenation during one-lung ventilation depends on reflex vasoconstriction in the nonventilated lung. In vitro, desflurane inhibits this reflex dose-dependently. Our results indicate that, in vivo, this does not necessarily translate to dose-dependent decreases in oxygenation during one-lung ventilation.

	Introduction

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Arterial oxygenation is impaired during one-lung ventilation (OLV). The degree of impairment depends, among other factors, on the extent of hypoxic pulmonary vasoconstriction (HPV). This important regulatory mechanism diverts blood flow away from hypoxic to better oxygenated areas of the lung. When changing from two-lung ventilation to OLV, HPV diverts blood flow from the nonventilated to the ventilated lung, thereby reducing venous admixture and ameliorating the decrease PaO₂.

In vitro, increasing concentrations of all volatile anesthetics directly depress HPV in a dose-dependent manner (1,2). In vivo, however, volatile anesthetics may affect HPV not only directly, but also indirectly, by their influence on cardiac output (CO), venous oxygen saturation, and shunt fraction. It is therefore rather difficult to predict to what extent increasing concentrations of volatile anesthetics will affect oxygenation in vivo. Accordingly, it was the goal of this study to evaluate the effects of increasing concentrations of desflurane on oxygenation during OLV in vivo. In vitro, desflurane depresses HPV in a dose-dependent manner (2).

	Methods

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The study protocol was approved by the Animal Protection Committee of the City of Freiburg, Germany. Thirteen male pigs (25–30 kg) were studied. After overnight fasting, the animals were premedicated with flunitrazepam (0.4 mg/kg IM) to allow placement of an IV line and continuous electrocardiography and pulse oximetry monitoring. After breathing oxygen, anesthesia was induced with propofol (2–3 mg/kg IV) and vecuronium (0.2 mg/kg IV), and the trachea was orally intubated with a 6.5- to 7.5-mm inner diameter endotracheal tube. Mechanical ventilation was provided by a constant-volume ventilator. Minute ventilation was adjusted to maintain PaCO₂ at approximately 40 mm Hg. Anesthesia was maintained with a 1:1 mixture of nitrous oxide (N₂O) and oxygen (O₂), desflurane 3% end-tidal (measured by Capnomac® Ultima; Datex, Helsinki, Finland), and continuous infusions of propofol (50 µg · kg^-1 · min^-1) and vecuronium (0.2 mg · kg^-1 · h^-1). This dose of vecuronium provides satisfactory relaxation while allowing movement of the animal if anesthesia is inadequate (3). Using sterile technique, a femoral arterial and a flow-directed thermodilution pulmonary artery catheter (right jugular vein) were introduced via cut downs. The tip of the pulmonary artery catheter was positioned just beyond the pulmonary valve to ensure placement in the main pulmonary artery (i.e., the catheter was not advanced to the wedge position). Subsequently, a tracheotomy was performed, and the orotracheal tube was replaced under fiberoptic control by a left-sided, 28F, double-lumen tube (DLT). Correct placement of the DLT was reconfirmed postmortem by autopsy.

After DLT placement, N₂O and desflurane were discontinued, and propofol was increased to 200 µg · kg^-1 · min^-1, a dose that produces adequate surgical anesthesia in the pig) (4,5). Subsequently, OLV (left lung) was started, and the fraction of inspired oxygen (FIO₂) in air was adjusted at 0.8. Correct OLV was verified by auscultation, by capnography from each lung, or by fiberoptic bronchoscopy. After recording stable cardiorespiratory variables (mean arterial pressure, pulse rate, end-tidal carbon dioxide concentration, O₂ saturation via pulse oximetry) for 10 min, propofol was discontinued, and anesthesia was continued in random order with desflurane 5% (0.5 minimum alveolar anesthetic concentration [MAC]), 10% (1 MAC), or 15% (1.5 MAC) end-tidal concentrations. Because desflurane was administered at various concentrations, particular care was taken to adjust the FIO₂ at 0.8 when changing between desflurane concentrations. Respiratory and hemodynamic variables were determined at each desflurane concentration after equilibration times of at least 20 min and after end-tidal concentrations had been stable for at least 10 min.

The animals were kept in the supine position throughout the experiment. Body temperature was continuously monitored by the thermistor of the thermodilution catheter. It was maintained by placing the animals on a heating pad and by warming the IV fluids. The animals received 4–6 mL · kg^-1 · h^-1 isotonic sodium chloride solution.

Shunt fraction was calculated using the standard formula: Qs/Qt = (CcO₂ - CaO₂)/(CcO₂ - CvO₂), where CcO₂ = capillary, CaO₂ = arterial, and CvO₂ = mixed venous oxygen content. The data were statistically analyzed by using Friedman's test using the Statistical Package for the Social Sciences® (SPSS, Chicago, IL) version 7.5. A P value of <0.05 was considered statistically significant.

	Results

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During OLV, PaO₂ did not change with increasing desflurane concentrations (Table 1). Mixed venous O₂ tension (PvO₂), mixed venous O₂ saturation (SvO₂), mean pulmonary and systemic arterial pressures, CO, and Qs/Qt decreased during desflurane anesthesia in a dose-dependent fashion. PaCO₂, arterial pH, tidal volume, and peak airway pressure were unchanged throughout the study.

	Discussion

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It has been shown that the in vitro determined dose-dependent inhibition of HPV by isoflurane (6) is also operative in vivo (7). Increasing concentrations of isoflurane administered locally to the hypoxic lung were accompanied by increasing intrapulmonary shunt and decreasing systemic oxygenation (7). Therefore, a direct dose-dependent inhibition of HPV by desflurane cannot be excluded in our study but might have been counteracted by associated hemodynamic alterations.

A variety of hemodynamic alterations associated with the use of desflurane are known to modify HPV (1,8). Such modifying effects on HPV might have maintained oxygenation in vivo, even if desflurane had exhibited direct dose-dependent inhibition of HPV. CO is one factor that may obscure the direct effects of volatile anesthetics on HPV in vivo. Other studies have shown that the magnitude of HPV is flow-dependent (1,7,9). Because most volatile anesthetics decrease CO in a dose-related fashion, the net effect of increasing concentrations of volatile anesthetics on oxygenation is probably the net result of dose-dependent direct inhibiting and indirect enhancing effects on HPV. In our study, CO decreased progressively with increasing concentrations of desflurane. This may have attenuated any direct dose-dependent inhibition of desflurane on HPV.

PvO₂ is another factor that may modify the HPV response in vivo. Decreases in PvO₂ may enhance HPV (1,10). In our study, desflurane led to dose-dependent decreases in PvO₂. Thus, decreasing PvO₂ during higher concentrations of desflurane may have, in part, counteracted the increasing direct inhibitory effects of desflurane on HPV, thereby maintaining oxygenation during increasing desflurane concentrations.

In support of our assumption that CO and PvO₂ might have modified the direct effects of desflurane on HPV, Qs/Qt decreased dose-dependently. In this study, any prominent direct inhibitory effect of desflurane on HPV should have resulted in an increase in Qs/Qt with increasing desflurane concentrations. Our finding that Qs/Qt actually decreased with increasing desflurane concentrations suggests that in vitro inhibition of HPV by volatile anesthetics does not necessarily translate to in vivo increases in Qs/Qt.

Why did the dose-dependent decrease in shunt volume during desflurane anesthesia not lead to a corresponding increase in oxygenation? Most likely because, at a given intrapulmonary shunt volume, decreases in the oxygen content of the shunted (venous) blood will lead to corresponding decreases in systemic oxygenation (11). Thus, during OLV, decreases in mixed venous oxygenation may, on the one hand, improve systemic oxygenation by enhancing HPV and reducing shunt volume (reducing flow to the nonventilated lung) but may, on the other hand, impair systemic oxygenation by admixture of venous blood with low oxygen saturation. In our study, there were no significant changes in PaO₂ during increasing concentrations of desflurane, probably because of the modifying and interactive effects of PvO₂, CO, and Qs/Qt.

In conclusion, our findings indicate that increasing concentrations of desflurane do not necessarily increase Qs/Qt or worsen oxygenation during OLV in vivo. A direct dose-dependent inhibition of HPV by desflurane [as described in vitro (2)] cannot be excluded and might have been counteracted by associated hemodynamic alterations that intensify HPV.

	References

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8. Eger EI II. Physicochemical properties and pharmacodynamics of desflurane. Anaesthesia 1995;50:3–8.
9. Lennon PF, Murray PA. Attenuated hypoxic pulmonary vasoconstriction during isoflurane anesthesia is abolished by cyclooxygenase inhibition in chronically instrumented dogs. Anesthesiology 1996;84:404–14.[Web of Science][Medline]
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11. Nunn JF. Distribution of pulmonary ventilation and perfusion. In: Nunn JF, ed. Applied respiratory physiology. London:Butterworths, 1993:156–97.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999