Cardiopulmonary and acid–base effects of desflurane and sevoflurane in spontaneously breathing cats

Journal of Feline Medicine and Surgery (2005) 7, 95e100 doi:10.1016/j.jfms.2004.06.003

Cardiopulmonary and acidebase effects of desflurane and sevoflurane in spontaneously breathing cats Almir Pereira Souza DVM, MS, PhD1, Piedad Natalia Henao Guerrero DVM, MS1, Celina Tie Nishimori DVM, MS1, Danielli Parrilha Paula DVM, MS1, Paulo Sergio Patto Santos DVM, MS, PhD2, Marlis Langenegger de Rezende DVM, MS, PhD1, Newton Nunes DVM, MS, PhD1* 1 Department of Veterinary Clinics and Surgery, Veterinary Surgery Program, Faculdade de Cieˆncias Agra´rias e Veterina´rias, Universidade Estadual Paulista, Rod. Professor Paulo Donato Castelane, s/n. CEP: 14884-900, Jaboticabal, SP., Brazil 2 Centro Universita´rio Bara˜o de Maua´, Ribeira˜o Preto, SP., Brazil

Date accepted: 23 June 2004

The cardiopulmonary effects of desflurane and sevoflurane anesthesia were compared in cats breathing spontaneously. Heart (HR) and respiratory (RR) rates; systolic (SAP), diastolic (DAP) and mean arterial (MAP) pressures; partial pressure of end tidal carbon dioxide (PETCO2), arterial blood pH (pH), arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2); base deficit (BD), arterial oxygen saturation (SaO2) and bicarbonate ion concentration (HCO3) were measured. Anesthesia was induced with propofol (8 G 2.3 mg/kg IV) and maintained with desflurane (GD) or sevoflurane (GS), both at 1.3 MAC. Data were analyzed by analysis of variance (ANOVA), followed by the Tukey test (P ! 0.05). Both anesthetics showed similar effects. HR and RR decreased when compared to the basal values, but remained constant during inhalant anesthesia and PETCO2 increased with time. Both anesthetics caused acidemia and hypercapnia, but BD stayed within normal limits. Therefore, despite reducing HR and SAP (GD) when compared to the basal values, desflurane and sevoflurane provide good stability of the cardiovascular parameters during a short period of inhalant anesthesia (T20eT60). However, both volatile anesthetics cause acute respiratory acidosis in cats breathing spontaneously. Ó 2004 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

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esflurane is a halogenated fluorinated volatile anesthetic that has been routinely used since 1992 (Weiskopf et al 1992). Desflurane’s low blood/gas partition coefficient (0.42) allows fast changes in its alveolar concentration, producing fast anesthetic induction and recovery (Eger 1992). Rapid changes in desflurane concentration during its administration are associated with an increase of sympathetic activity, with a peak at 5 min of exposure to the anesthetic agent (Pacentine et al 1995). It depresses myocardial contractility thus reducing cardiac output (Pagel et al 1991). It also inhibits spontaneous ventricular arrhythmias after myocardial infarction (Novalija et al 1998). In cats, when the effects of 1.7 and 1.3 MAC were

*Corresponding author. E-mail: [email protected]

1098-612X/04/020095+06 $30.00/0

compared, it was observed that the higher concentration caused a reduction of systolic arterial pressures (only with controlled ventilation), and hypercapnia, but did not affect the cardiac index (McMurphy and Hodgson 1996). Sevoflurane is a non-flammable isopropylic fluorited ether. This inhalant anesthetic affects the cardiovascular system by reducing the mean arterial pressure, lowering myocardial contractility (without sensitizing the myocardium to the action of epinephrine (Navarro et al 1994)), and slightly increasing the heart rate (Bernard et al 1990, Kawana et al 1995). When compared to the effects of other volatile anesthetics used in humans, sevoflurane seems to be the one that offers greater cardiovascular stability (Ebert et al 1995). In cats, the degree of hypercapnia and acidosis produced by sevoflurane does not differ from that caused by isoflurane, and is less than

Ó 2004 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

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that induced by halothane or enflurane (Hikasa et al 1997). Studies comparing sevoflurane with other anesthetic agents in cats have been undertaken (Hikasa et al 1996). However, studies comparing sevoflurane with desflurane are still needed. The aim of this study was to compare some of the cardiopulmonary and acidebase effects of desflurane and sevoflurane in clinically healthy cats breathing spontaneously.

Materials and methods This study was approved by the Animal Care Committee at Universidade Estadual Paulista e UNESP/Jaboticabal. Twelve clinically healthy adult cats (3.2 G 0.6 kg) were used. The cats were housed individually in stainless steel cages and fed commercial dry food and water ad libitum. Food was withheld 12 h before anesthesia. After fully recovery from anesthesia, the animals were returned to their cages and fed as described previously. Anesthetic procedures

The cats were divided into two groups of six animals each (GD and GS). All cats were induced with intravenous propofol (Diprivan; Zeneca) at 8 G 2.3 mg/kg and were intubated with endotracheal tubes (size range: 3.0e4.0). Anesthesia was maintained with desflurane (Suprane; Zeneca) in the GD group, and with sevoflurane (Sevorane; Abbott) in the GS group, both diluted in 100% oxygen at a flow rate of 30 ml/kg/min, through a partial rebreathing anesthetic circuit (Excel 210SE; Ohmeda) and calibrated vaporizers for each agent (TEC 6; Ohmeda and Sevotec 5; Ohmeda). Both anesthetics were administered at 1.3 MAC. One MAC was considered to be 9.79V% for desflurane (McMurphy and Hodgson 1995) and 2.6V% for sevoflurane (Hikasa et al 1996). The anesthetic concentrations were measured using a gas analyzer (Ohmeda 5220; Ohmeda) that has a system of automatic calibration which uses sealed samples of the gases. It was adjusted to calibrate immediately before each measurement. The animals were placed in right lateral recumbency on a surgical table and volatile anesthesia was maintained during 60 min while the animals were allowed to breathe spontaneously. Body temperature was maintained within normal limits (37.9 G 0.78(C) throughout the experiment by the use of a circulating warmwater blanket (Gaymar TP500; Gaymar).

At 60 min after the onset of anesthesia, the anesthetic circuit was disconnected from the animal. The endotracheal tube was removed immediately after the return of swallowing movements. Cardiopulmonary measurements

The following parameters were measured: - heart rate (HR), using the ReR interval, obtained from a computerized electrocardiograph (Teb ECGPC 1.10; Teb); - systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures, measured at time zero (T0) using an oscillometric pressure monitor (Dixtal 2010; Dixtal Biomedica) and at the following measurements (described below) during T20eT60 using an 18G femoral arterial catheter, and connected to a domus type pressure transducer (positioned at the heart level and adjusted to measure 0 mmHg at atmospheric pressure) of a computerized digital monitor (Dixtal 2010; Dixtal Biomedica); respiratory rate (RR) and partial pressure of end tidal carbon dioxide (PETCO2), obtained through an oxycapnograph with a nasal adaptor placed at the nostrils (Dixtal mod. CO2SMO 7100; Dixtal Biomedica) at the baseline and through a multiparametric monitor (Dixtal 2010; Dixtal Biomedica) with the sensor placed between the tracheal tube and the anesthesia circuit; - arterial pH (pH), arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), plasma bicarbonate (HCO3), base deficit (BD) and arterial oxygen saturation (SaO2) were measured from arterial blood samples, drawn from the femoral artery, and immediately analyzed by a digital blood gas analyzer (Portable Clinical Analyzer I-STAT; Sensor Devices), which is designed to calibrate automatically each time a new cartridge is inserted.

Before the anesthetic induction, the hair was clipped from the right femoral triangle and 1 ml of lidocaine cloridrate (Xylestesin; Crista´lia) was infiltrated over the femoral artery. The femoral artery was then exposed through a skin incision to allow puncture of the artery in order to collect the first blood sample (T0). For the other measurements (T20eT60) the blood samples were collected through the same catheter used for the measurement of the arterial blood pressure.

Cardiopulmonary and acidebase effects

The measurements were taken before the induction of the anesthesia (T0) and at 20 min (T20), 40 min (T40) and 60 min (T60) of volatile anesthesia. Statistical analyses

Data were analyzed by one-way analysis of variance for repeated measurements to compare time-related variables within each anesthetic group and Tukey’s multiple comparison test was used to identify differences between groups. The significance level of all tests was set at 5%.

Results The HR and RR of both groups were significantly reduced from the baseline with the administration of the volatile anesthetics, but remained stable during anesthesia (T20eT60). There were no differences between the agents used (Table 1). Regarding the arterial pressures (SAP, DAP and MAP), no differences between groups were observed. There was a tendency for lower values over time but it was not statistically significant, except the SAP, that in GD decreased significantly from the baseline (116 G 4) compared to 20 and 40 min (83 G 24; 85 G 16) of anesthesia. PETCO2 significantly increased in both groups after the beginning of anesthesia (T20) and remained high thereafter. The blood gas analyses showed a significant reduction of the pH baseline values with the administration of the inhalant anesthetics. They

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continued to be low until the end of anesthesia (Table 2). It was expected to obtain lower PaO2 values in GD. This was confirmed by the statistical analysis, which showed a difference between the groups throughout the experimental period with GD having the lower values (T20eT60). However, the PaO2 values remained constant within the groups during anesthesia. The PaCO2 increased in both groups with anesthesia (T20) and remained constant until the end of the experimental period. Statistical difference between groups was observed only at T20 where GD mean value of PaCO2 was lower than that of GS. SaO2 remained at 100% for both groups throughout the anesthetic period. BD and HCO3 did not change significantly during anesthesia within groups. However, when comparing the results between groups, BD was significantly higher in GD than in GS. HCO3 values were lower with desflurane than with sevoflurane.

Discussion The influence of the pharmacological properties of the inhalant anesthetics is better observed with spontaneous than with mechanical ventilation (Mutoh et al 1997). As the aim of this study was to compare the cardiopulmonary effects of desflurane and sevoflurane under clinical conditions, spontaneous ventilation was the chosen technique. Anesthesia was induced with propofol, because in clinical conditions it is unusual to use

Table 1. Mean values (G standard deviations) for heart (HR) and respiratory (RR) rates; partial pressure of end tidal carbon dioxide (PETCO2), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures of cats anesthetized with desflurane (GD) or sevoflurane (GS) Variables

T0

T20 a

T40 b

T60 b

HR (beats/min)

GD GS

197 G 9.77 211 G 19.11a

135 G 20.77 145 G 21.19b

132 G 18.64 151 G 25.23b

129 G 12.74b 145 G 22.84b

RR (breath/min)

GD GS

40 G 5.79a 52 G 14.84a

18 G 5.5b 16 G 4.8b

21 G 6.68b 18 G 5.73b

22 G 7.56b 18 G 6.75b

PETCO2 (mmHg)

GD GS

32 G 1.21 34 G 2.88a

34 G 7.55 43 G 0.82ab

39 G 6.52 45 G 5.09b

43 G 5.79 47 G 7.94b

SAP (mmHg)

GD GS

116 G 4.41a 112 G 8.99

83 G 23.8b 85 G 8.95

85 G 16.06b 97 G 26.74

90 G 20.67ab 92 G 8.57

DAP (mmHg)

GD GS

60 G 8.52 63 G 15.44

47 G 17.68 51 G 14.68

46 G 12.56 59 G 10.75

52 G 13.38 57 G 11.20

MAP (mmHg)

GD GS

79 G 9.14 74 G 7.90

63 G 22.72 66 G 13.63

64 G 15.72 75 G 13.87

67 G 20.63 74 G 10.97

Values followed by different letters in the line are significantly different among time points (P ! 0.05).

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Table 2. Mean values (G standard deviations) for arterial blood pH (pH), arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2); base deficit (BD), arterial oxygen saturation (SaO2) and bicarbonate ion concentration (HCO3) of cats anesthetized with desflurane (GD) or sevoflurane (GS) Variables

T0

T20 a

T40

T60

7.15 G 0.07 7.20 G 0.03b

7.14 G 0.06 7.23 G 0.04b

7.13 G 0.06b 7.24 G 0.03b

446 G 25.53b* 544 G 17.00b

448 G 26.6b* 558 G 6.68ab

25.5 G 3.0a 32.3 G 2.10a

435 G 18.2b* 520 G 30.14b 54.7 G 6.77b* 66.1 G 7.66b

58.0 G 7.69b 62.45 G 8.19b

60.2 G 2.75b 57.8 G 5.89b

GD GS

ÿ5.3 G 1.21 ÿ5 G 1.79

ÿ6.8 G 0.75 ÿ3.3 G 1.75*

ÿ5.8 G 2.14 ÿ2.2 G 2.04*

ÿ6.17 G 1.94 ÿ1.7 G 2.16*

SaO2 (%)

GD GS

96.5 G 1.05 94.7 G 4.9

100 G 0.0 100 G 0.0

100 G 0.0 100 G 0.0

100 G 0.0 100 G 0.0

HCO3 (mEq/l)

GD GS

16 G 3.06 19 G 1.21

pH

GD GS

7.30 G 0.10 7.39 G 0.04a

PaO2 (mmHg)

GD GS

89 G 8.08a 81 G 7.19a

PaCO2 (mmHg)

GD GS

BD (mEq/l)

b

19 G 2.51* 25 G 2.25

b

20 G 3.39* 25 G 2.23

20 G 2.88* 25 G 2.14

Values followed by different letters in the line are significantly different among time points (P ! 0.05). *Significantly different between groups (P ! 0.05).

only an inhalant agent. However, in order to avoid the possible effects of propofol over the variables in study, measurements were started 20 min after propofol administration as the clinical effects of propofol can no longer be detected after this time (Cullen et al 1991, Ilkiw et al 1992). The stability of the arterial pressure at T20, T40 and T60 also supports the absence of any residual effect of propofol. The cardiovascular alterations observed with desflurane and sevoflurane were similar, with no statistical differences between groups. Studies have shown that sevoflurane causes an increase in HR (Hikasa et al 1996, Mutoh et al 1997). Even though our findings showed a decrease in HR when compared to the baseline, this is probably due to the fact that at baseline the cats were awake and may have had their HR increased by an endogenous, stresseresponse epinephrine release. Cardiovascular stability and myocardial protection against catecholamine are important characteristics of sevoflurane (Navarro et al 1994, Hikasa et al 1996), which could explain the reduction and maintenance of the HR within normal limits. Although desflurane administration has been associated with an increase in sympathetic activity (Pacentine et al 1995), it also caused reduction and stability of HR in the cats in this study. This could be explained by the fact that the sympathetic stimulation has its peak at 5 min of exposure (Pacentine et al 1995) and our first measurement during anesthesia was realized only after 20 min of administration.

Arterial pressures (AP) decreased slightly in both groups, which could be attributed to a decrease in the systemic vascular resistance (SVR) caused by the volatile anesthetics (Navarro et al 1994, Clarke et al 1996, Santos et al 2003). Although no studies document the change in cardiac output (CO) from awake to anesthetized with desflurane or sevoflurane, a reduction of the CO is another factor that could have contributed to the AP decrease. Considering that we used an invasive technique to measure the AP during the anesthetic period but the less invasive oscillometric technique in the awake animals, the comparison between these data must be interpreted cautiously. Inhalant anesthetics in general, decrease arterial pressure in a dose dependent manner (Steffey 1996). As a fixed MAC was used for both agents, an initial reduction followed by stability of the AP during anesthesia was observed. Only in GD, SAP decreased after the beginning of anesthesia, which could be due to the reduction of SVR or myocardial contractility as addressed before. One cat in GD showed mean arterial pressures close to 40 mmHg during desflurane anesthesia, resulting in a decrease in the group mean values for this parameter. This could explain why the values observed for desflurane anesthesia were lower than the ones reported by McMurphy and Hodgson (1996) and Hikasa et al (1996). The RR decreased and PETCO2 increased with anesthesia in both groups. The PETCO2 increase could be explained by the RR decrease, assuming that the tidal volume was decreased or

Cardiopulmonary and acidebase effects

maintained constant. Although the tidal volume was not measured in this study, a decrease in the tidal volume is very common in anesthesia with spontaneous ventilation. In the sevoflurane group PETCO2 values were higher at 40 and 60 min of anesthesia when compared to baseline. Besides the RR reduction, it is possible that the depression of the ventilatory centers in the CNS and the relaxation of the intercostal muscles (Guyton 1992, Michell 1994) might have reduced the alveolar ventilation and contributed to the rise of PETCO2. McMurphy and Hodgson (1996) and Hikasa et al (1996) report higher values of RR than the ones observed in our study. This could be explained by the fact that in these two studies the cats were induced with an inhalant agent, and in our study we used propofol. As propofol is a respiratory depressant, the lower RR could be due to a residual effect of this anesthetic drug. However, studies of Cullen et al (1991) and Ilkiw et al (1992) have reported that 20e30 min after propofol administration, the physiologic variables return to the values prior to administration. Comparing the PETCO2 and the PaCO2 values, differences of nearly 20 mmHg can be noted, suggesting dilution of the samples. Although no leaking was noticed in the circuit, we cannot exclude this possibility. Arterial pH was significantly reduced by anesthesia (T20) in both groups. The acidemia is due to a respiratory component, suggesting that both anesthetics may cause respiratory acidosis in cats although this effect was not observed in dogs (Clarke et al 1996, Mutoh et al 1997). The PaO2 was consistently lower with desflurane than with sevoflurane, which could be due to the higher concentration required by desflurane (12.7% vs. 3.4% for sevoflurane, both at 1.3 MAC). This would reflect a much higher partial pressure as well (97 mmHg vs. 26 mmHg for sevoflurane, both at 1 atmosphere). The fact that the inspired oxygen tension would have been at least 71 mmHg lower for the desflurane animals could account for the differences in PaO2. The normal PaCO2 for cats is 34 G 7 mmHg (Hikasa et al 1996). Based on these values, the cats of this study became hypercapneic during anesthesia. The results of the blood gas analyses showed that the levels of hypercapnia and acidemia in GD and GS were similar to the ones described in other studies (McMurphy and Hodgson 1996, Hikasa et al 1996). The

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hypercapnia is due to hypoventilation. Anesthesia depresses the ventilatory centers causing a decrease in RR, as observed in this study. The reduction of the RR probably decreases the respiratory minute ventilation which causes hypoventilation. Tidal volume usually decreases with anesthesia as well and even though the respiratory volumes were not measured, the RR reduction associated with the decrease or even the maintenance of the tidal volume can explain the elevation of the PaCO2 (McMurphy and Hodgson 1996) and consequently the respiratory acidosis. Bicarbonate (HCO3) is one of the most important chemicals used by the body to neutralize the excess of HC in acidosis (Guyton 1992). Given that the normal range for the cat is 17e22 mEq/l (Haskins and Aldrich 1994), in this study, HCO3 levels stayed within normal limits in GD and were slightly increased in GS. These findings were expected considering that a metabolic compensation for a respiratory abnormality does not occur acutely (Rose and Post 2001). Regarding the BD, its values were within the normal limits (ÿ1 to ÿ8) (Haskins and Aldrich 1994), showing no significant contribution to the pH disturbance. It confirms that the alterations were respiratory rather than metabolic (Muir and Hubbell 1997). The results allow us to conclude that desflurane and sevoflurane offer good cardiovascular stability, but cause respiratory acidosis in spontaneously breathing cats.

Acknowledgements This study was funded by Fundac¸a˜o de Amparo a Pesquisa do Estado de Sa˜o Paulo - FAPESP.

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