Effects of desflurane, sevoflurane and isoflurane on pulmonary shunt in dogs during spontaneous ventilation

Efeitos do desflurano, sevoflurano e isoflurano sobre o shunt pulmonar em cães sob respiração espontânea

Abstracts

The aim of this study was to compare the effects of desflurane, sevoflurane and isoflurane on pulmonary shunt in dogs during spontaneous ventilation. General anesthesia was induced in 30 healthy, adult, mongrel dogs by intravenous administration of propofol. The animals were separated into three groups of 10 dogs each and submitted to general inhalation anesthesia with 1.5 MAC of desflurane (G1), sevoflurane (G2) and isoflurane (G3). Arterial blood was collected by puncture of the right femoral artery, and mixed blood was collected by introducing a Swan-Ganz catheter into the pulmonary artery. These samples were used to determine the parameters employed for calculation of the intrapulmonary shunt. Measurements began at 20min after orotracheal intubation and were repeated every 20min, totaling six measurements. Means were compared by the Student t-test (P<FONT FACE=Symbol>£</FONT> 0.05). Desflurane led to a higher shunt than sevoflurane and isoflurane at 40 and 60min. At 80min, the mean values obtained for desflurane were higher than those obtained for isoflurane, while at 100min the values observed for dogs anesthetized with desflurane were higher than those obtained with sevoflurane. Desflurane caused respiratory depression by reducing PaO2, and a higher percentage of intrapulmonary shunt than isoflurane and sevoflurane.

dog; intrapulmonary shunt; desflurane; isoflurane; sevoflurane

O estudo teve por objetivo avaliar os efeitos de três anestésicos inalatórios sobre o shunt pulmonar em cães sob ventilação espontânea. Trinta cães foram separados e protocolados em três grupos (G) de 10 cães cada. Induziu-se a anestesia geral por meio da administração intravenosa de propofol. Em seguida procedeu-se à anestesia geral inalatória pelo desflurano (G1), sevoflurano (G2) ou isoflurano (G3) na concentração de 1,5 CAM. Para a determinação dos parâmetros utilizados nas equações para cálculo do shunt intrapulmonar foram colhidos sangue arterial por punção da artéria femoral direita, e sangue misto, por meio de cateter de Swan-Ganz, posicionado na artéria pulmonar. As mensurações tiveram início 20min após a intubação orotraqueal e se repetiram a cada 20min, num total de seis colheitas. Contrastes de médias foram feitos pelo teste t de Student (P<FONT FACE=Symbol>£</FONT> 0,05). O desflurano apresentou shunt pulmonar superior aos apresentados pelo sevoflurano e isoflurano aos 40 e 60min. Aos 80min, os valores médios obtidos com o desflurano foram superiores aos obtidos pelo isoflurano, enquanto que aos 100min foram mais elevados do que os obtidos pelo sevoflurano. O desflurano, quando comparado ao isoflurano e ao sevoflurano, produziu depressão respiratória pela redução da PaO2, determinando maior percentagem de shunt intrapulmonar.

cão; shunt pulmonar; desflurano; isoflurano; sevoflurano

Effects of desflurane, sevoflurane and isoflurane on pulmonary shunt in dogs during spontaneous ventilation

Efeitos do desflurano, sevoflurano e isoflurano sobre o shunt pulmonar em cães sob respiração espontânea

N. Nunes; S.E.C. Martins; P.S.P. Santos; M.L. Rezende

Faculdade de Ciências Agrárias e Veterinárias da UNESP - Campus de Jaboticabal Rodovia Paulo Donato Castellane s/n°, Zona Rural 14870-000 - Jaboticabal, SP

ABSTRACT

The aim of this study was to compare the effects of desflurane, sevoflurane and isoflurane on pulmonary shunt in dogs during spontaneous ventilation. General anesthesia was induced in 30 healthy, adult, mongrel dogs by intravenous administration of propofol. The animals were separated into three groups of 10 dogs each and submitted to general inhalation anesthesia with 1.5 MAC of desflurane (G1), sevoflurane (G2) and isoflurane (G3). Arterial blood was collected by puncture of the right femoral artery, and mixed blood was collected by introducing a Swan-Ganz catheter into the pulmonary artery. These samples were used to determine the parameters employed for calculation of the intrapulmonary shunt. Measurements began at 20min after orotracheal intubation and were repeated every 20min, totaling six measurements. Means were compared by the Student t-test (P£ 0.05). Desflurane led to a higher shunt than sevoflurane and isoflurane at 40 and 60min. At 80min, the mean values obtained for desflurane were higher than those obtained for isoflurane, while at 100min the values observed for dogs anesthetized with desflurane were higher than those obtained with sevoflurane. Desflurane caused respiratory depression by reducing PaO₂, and a higher percentage of intrapulmonary shunt than isoflurane and sevoflurane.

Keywords: dog, intrapulmonary shunt, desflurane, isoflurane, sevoflurane

RESUMO

O estudo teve por objetivo avaliar os efeitos de três anestésicos inalatórios sobre o shunt pulmonar em cães sob ventilação espontânea. Trinta cães foram separados e protocolados em três grupos (G) de 10 cães cada. Induziu-se a anestesia geral por meio da administração intravenosa de propofol. Em seguida procedeu-se à anestesia geral inalatória pelo desflurano (G1), sevoflurano (G2) ou isoflurano (G3) na concentração de 1,5 CAM. Para a determinação dos parâmetros utilizados nas equações para cálculo do shunt intrapulmonar foram colhidos sangue arterial por punção da artéria femoral direita, e sangue misto, por meio de cateter de Swan-Ganz, posicionado na artéria pulmonar. As mensurações tiveram início 20min após a intubação orotraqueal e se repetiram a cada 20min, num total de seis colheitas. Contrastes de médias foram feitos pelo teste t de Student (P£ 0,05). O desflurano apresentou shunt pulmonar superior aos apresentados pelo sevoflurano e isoflurano aos 40 e 60min. Aos 80min, os valores médios obtidos com o desflurano foram superiores aos obtidos pelo isoflurano, enquanto que aos 100min foram mais elevados do que os obtidos pelo sevoflurano. O desflurano, quando comparado ao isoflurano e ao sevoflurano, produziu depressão respiratória pela redução da PaO₂, determinando maior percentagem de shunt intrapulmonar.

Palavras-chave: cão, shunt pulmonar, desflurano, isoflurano, sevoflurano

INTRODUCTION

Intrapulmonary shunt is defined as the blood passing from the right to the left side of the circulation without being oxygenated (Haskins, 1996). The understanding of the effects of anesthetic agents on shunt values allows the anticipation of possible changes in tissue oxygenation capacity, since elevated shunt values induced by anesthesia lead to lower oxygen transport rates.

The use of the Swan-Ganz catheter represented a significant advance for monitoring critically ill patients in intensive care units or in surgical facilities. For patients with acute respiratory failure or other respiratory pathologies, the advent of this technology allowed calculation of the percentage of intrapulmonary shunt, which in turn contributes to the assessment of prognosis and selection of therapeutic procedures (Kreienbühl et al., 1975).

In addition, development of new anesthetic drugs provides new resources for the anesthesiologist, which may help to minimize the risks inherent to routine anesthetic procedures. Therefore, the study of recently developed drugs and their comparison with commonly used ones might be of great value, especially with respect to their effects on poorly investigated physiological variables.

Desflurane is a relatively new agent and the latest to be introduced into the routine of large hospital centers. It is a halogenated, fluorinated volatile anesthetic, which was introduced into clinical practice in 1992 (Weiskopf, 1992). The low blood/gas coefficient of desflurane (0.42) gives a rapid increase or decrease in alveolar concentration, leading to rapid anesthesia induction and patient recovery (Eger, 1992). However, induction of anesthesia with a mask is not recommended due to the irritating action of desflurane on the mucosa. The use of desflurane in adult and pediatric patients has been associated with cough and laryngospasm (Tinker, 1992).

Administration of desflurane has been correlated with an increase in sympathetic activity, which reaches a maximum peak at 5min after exposure to the drug (Pacentine et al., 1995). The sympathomimetic action of desflurane is due to receptor sites in the upper airways, which respond rapidly to increases in concentration of this gas in the alveoli (Muzi et al., 1996).

Desflurane causes a dose-dependent increase in minute volume, an increased respiratory rate and depression in the ventilatory response to CO₂, which are directly related to the concentration of the anesthetic used with or without nitrous oxide. Partial arterial CO₂ pressure (PaCO₂) increases according to the depth of the anesthesia (Clarke et al., 1996). Lockhart et al. (1991) observed depression of spontaneous ventilation in humans caused by desflurane alone or in combination with nitrous oxide.

Sevoflurane is also a halogenated, fluorinated volatile anesthetic, which causes a decrease in arterial pressure and cardiac output as well as an increase in the heart rate (Kawana et al., 1995). In contrast, sevoflurane causes vasodilatation of coronary vessels, thus reducing vascular resistance (Kersten et al., 1994). With respect to respiratory depression, sevoflurane and halothane at a concentration of 1.1 minimum alveolar concentration (MAC) show a similar intensity, while at 1.4 MAC sevoflurane leads to more profound pulmonary depression. Both sevoflurane and halothane induce a reduced CO₂ response and increased PaCO₂ with the deepening of anesthesia (Doi, Ikeda, 1987).

Isoflurane, a volatile anesthetic also belonging to the group of halogenated, fluorinated anesthetics, has a MAC of 1.28 V%, which does not change with the time of anesthesia (Steffey, Howland, 1977; Steffey et al., 1979). Prolonged or very deep anesthesia with isoflurane causes minimal changes in blood cell count and biochemical values, maintaining a stable cardiovascular function and heart beat (Steffey, Howland, 1980). There is evidence that, depending on the anesthetic dose, isoflurane may reduce the respiratory rate in felines (Steffey et al., 1979).

Data on changes in patient physiology induced by desflurane and, particularly, comparisons between changes induced by desflurane, sevoflurane and isoflurane are scarce. Therefore, the aim of this study was to compare the effects of desflurane, sevoflurane and isoflurane on pulmonary shunt values in dogs.

MATERIAL AND METHODS

This experiment was performed following the Jaboticabal Campus Animal Care and Use Committee guidelines. Thirty healthy, adult mongrel dogs of both sexes, excluding pregnant females or females in estrus, were provided by the Hospital Veterinário "Governador Laudo Natel", Faculdade de Ciências Agrárias e Veterinárias - FCAV/UNESP, Jaboticabal Campus, SP. The animals were randomly divided into three groups of 10 dogs each (G1, G2, and G3).

General anesthesia was induced in all animals by intravenous administration of 10 mg/kg (± 1.3 mg/kg) propofol _{(Diprivan – Zeneca Farmacêutica do Brasil Ltda. São Paulo – SP)}. The animals were immediately intubated and submitted to general inhalation anesthesia with desflurane _{(Suprane - Zeneca Farmacêutica do Brasil Ltda. São Paulo – SP)} (G1), sevoflurane _{(Sevorane – Abbott Laboratórios do Brasil Ltda. São Paulo – SP)} (G2) and isoflurane _{(Isoforine – Laboratório Cristália Ltda. Itapira – SP)} (G3). The anesthetics were administered at a dose of 1.5 MAC, which was measured with digital gas analyzer _{(Model 5220 – Ohmeda. Louisville – CO – USA)}, diluted in 100% oxygen at a flow rate of 30 ml/kg/min, using a semi-closed anesthetic circuit (Model Excel 210 SE – Ohmeda. Louisville – CO - USA) equipped with a vaporizer calibrated for each anesthetic agent.

Measurements started at 20 min after orotracheal intubation (T1) and were repeated every 20 min, totaling six measurements (T2, T3, T4, T5, and T6).

Arterial blood (0.5 ml) was collected by puncture of the right femoral artery for determination of the parameters used in the shunt calculation and was analyzed using a portable clinical analyzer _{(I – Stat – SDI Sensor Devices Inc. Waukesha – WI – USA).}

The intrapulmonary shunt (Qs/Qt) was obtained using a multiparametric monitor _{(Dixtal model 2010 – Dixtal Biomédica Ltda. São Paulo – SP)}, which calculates the intrapulmonary shunt based on the equations of Leigth et al. (1969). Collection of mixed blood for determination of values used for calculation of the formulas (PvO₂, SvO₂) was carried out according to a classical method, by introducing a Swan-Ganz catheter into the right or left jugular vein, with the tip of the catheter positioned in the pulmonary artery.

Means were compared by the Student t-test, with the level of significance at 5% (P£ 0.05).

Formulas used:

, where

Cc' O₂ = oxygen content in pulmonary distal capillary blood (ml/dl),

CaO₂ = oxygen content in arterial blood (ml/dl),

CvO₂ = oxygen content in mixed blood (ml/dl).

Then:

where

0.00139 = ml oxygen transported by 1g of hemoglobin (ml/g),

Hb = hemoglobin concentration in g/dl,

0.0031 = O₂ solubility coefficient in plasma,

PBar = local barometric pressure (Jaboticabal 960 mmHg),

PaCO₂ = partial CO₂ pressure in arterial blood (mmHg),

SaO₂ = oxyhemoglobin saturation in arterial blood (%),

PaO₂ = partial O₂ pressure in arterial blood (mmHg),

SvO₂ = oxyhemoglobin saturation in venous blood (%),

PvO₂ = partial CO₂ pressure in mixed blood (mmHg),

47 = correction factor of water vapor pressure (mmHg).

RESULTS AND DISCUSSION

Desflurane led to a higher shunt than sevoflurane and isoflurane at 40 and 60 min. At 80 min, the mean values obtained for desflurane were higher than those obtained for isoflurane, while at 100 min the values observed for dogs anesthetized with desflurane were higher than those obtained with sevoflurane (Table 1).

Desflurane is known to cause irritation of the mucosa (Young, Apfelbaum, 1995; Weiskopf et al., 1992). Although this fact may be associated with the results obtained for PaO₂ and PaCO₂, effects of the drug on the central nervous system or even on intercostal or diaphragm muscle tone, which impair the adequate filling of the lungs, cannot be excluded (Patel, Goa, 1995).

Regarding PaO₂, desflurane is responsible for a dose-dependent depression of the respiratory function (Patel, Goa, 1995). This fact, together with the effect of the drug on minute volume, may explain the low PaO₂ values obtained with desflurane compared to the other anesthetics studied. On the other hand, isoflurane was associated with a highly satisfactory respiratory performance, maintaining PaO₂ at ideal values (Haskins, 1996).

Doi et al. (1994), determining the respiratory effects of sevoflurane alone or in association with nitrous oxide during surgical stimulation, observed a reduction in PaCO₂ and an increase in tidal volume with a consequent increase in minute volume, when using 1.3 MAC sevoflurane plus 0.4 MAC nitrous oxide. In this case, spontaneous respiration maintained PaCO₂ at appropriate levels. In contrast, spontaneous respiration was moderately depressed at 1.6 MAC sevoflurane plus 0.4 MAC nitrous oxide, indicating a possible dose-dependent depressor effect of sevoflurane on the respiratory system.

Intrapulmonary shunt is defined as the whole blood passing from the right to the left side of the circulation without being oxygenated (Haskins, 1996). Among the variables used, PaO₂ plays an expressive role to calculate intrapulmonary shunt (Leigth et al., 1969). Dogs receiving desflurane had low PaO₂ compared to the other groups, thus explaining the fact that the Qs/Qt was below normal levels in this group (Cane et al., 1988). Patel and Goa (1995) suggested that in addition to the increase in the fraction of intrapulmonary shunt this characteristic of desflurane is responsible for a generalized depression of the respiratory system.

The use of desflurane in patients with respiratory pathologies is therefore not recommended since in addition to a reduction in PaO₂ this drug is responsible for an increase in the percentage of non-oxygenated blood passing through the lungs.

Based on these results, it is concluded that desflurane induces respiratory depression by reducing PaO₂ and causes a higher percentage of intrapulmonary shunt than isoflurane and sevoflurane.

ACKNOWLEDGMENTS

The authors thank the Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP for financial support.

Recebido para publicação em 27 de fevereiro de 2002

Recebido para publicação, após modificações, em 16 de agosto de 2002

E-mail: [e-mail]

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Publication Dates

• Publication in this collection
  15 July 2003
• Date of issue
  Apr 2003

History

• Accepted
  16 Aug 2002
• Received
  27 Feb 2002