Animal dependence of inhaled anaesthetic requirements in cats{dagger}

L. S. Barter*,1, J. E. Ilkiw1, E. P. Steffey1, B. H. Pypendop1 and A. Imai2

1 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, USA 2 Present address: B32-322-26-6 B Heiwa-Machi Kanazawa, Ishikawa 921-8105, Japan

*Corresponding author. E-mail: lsbarter@ucdavis.edu
{dagger}This study was presented in abstract form at the American College of Veterinary Anesthesiologists Annual Meeting in Orlando, Florida, October 2002.

Accepted for publication: August 19, 2003


    Abstract
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 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Background. The minimum alveolar concentration (MAC) of an inhaled anaesthetic describes its potency as a general anaesthetic. Individuals vary in their sensitivity to anaesthetics and we sought to determine whether an individual animal’s sensitivity to inhaled anaesthetics would be maintained across different agents.

Methods. Six female mongrel cats, age 2 yr (range 1.8–2.3) and mean weight 3.5 (SD 0.3) kg, were studied on three separate occasions over a 12-month period to determine the MAC of isoflurane, sevoflurane and desflurane. Induction of anaesthesia in a chamber was followed by orotracheal intubation and maintenance of anaesthesia with the inhaled agent in oxygen delivered via a non-rebreathing circuit. MAC was determined in triplicate using standard tail-clamp technique.

Results. Mean MAC values for isoflurane, sevoflurane and desflurane were 1.90 (SD 0.18), 3.41 (0.65) and 10.27 (1.06)%, respectively. Body temperature, systolic pressure and SpO2 recorded at the time of MAC determinations for isoflurane, sevoflurane and desflurane were 38.3 (0.3), 38.6 (0.1) and 38.3 (0.3)°C; 71.2 (8.3), 74.6 (15.9) and 88.0 (12.0) mmHg; 99.2 (1.1), 99.1 (1.3) and 99.4 (0.8)%, respectively. Both the anaesthetic agent and the individual cat had significant effects on MAC. Correlation coefficients for comparisons between desflurane and isoflurane, desflurane and sevoflurane, and sevoflurane and isoflurane were 0.90, 0.89 and 0.97, respectively.

Conclusions. These findings show that an individual has a consistent degree of sensitivity to a variety of inhaled anaesthetics, suggesting a genetic basis for sensitivity to inhaled anaesthetic effects.

Br J Anaesth 2004; 92: 275–7

Keywords: anaesthetics volatile, desflurane; anaesthetics volatile, isoflurane; anaesthetics volatile, sevoflurane; cat; lung, minimum alveolar concentration


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
The alveolar concentration of an inhaled anaesthetic that eliminates movement in 50% of subjects exposed to noxious stimulus is termed the minimum alveolar concentration (MAC). MAC is a commonly used indicator of anaesthetic potency and traditionally has been considered to vary little between and within species.1 There is experimental evidence that mice of different strains vary in their sensitivity to nitrous oxide, suggesting that a genetic basis to variations in anaesthetic requirement exists.2 Studies to date have investigated the sensitivity of individuals to a single anaesthetic agent and the sensitivity of genetically different populations to different agents.3 4 Consistency in the sensitivity of individuals to a variety of inhaled anaesthetics has not been convincingly demonstrated. Consequently we sought to test the hypothesis that an individual’s sensitivity to inhalation anaesthesia would be consistent across a variety of inhaled agents.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Six female domestic shorthaired (mongrel) cats, age 2 yr (range 1.8–2.3) and mean weight 3.5 (SD 0.3) kg, were studied on three separate occasions over a 12-month period with at least 4 weeks between each anaesthetic exposure. In each study the MAC for isoflurane, sevoflurane and desflurane was determined with the approval of the Animal Care and Use Committee, University of California, Davis. For induction of anaesthesia, cats were placed in an acrylic chamber into which the inhaled agent was delivered in oxygen with a gas flow rate of 6 litre min–1. Once anaesthetized, cats were removed from the chamber and their tracheas intubated with a cuffed 4.5 mm internal-diameter tube. Anaesthesia was maintained with the inhaled agent in oxygen delivered via a Bain circuit with fresh gas flow rates of 500 ml kg–1 min–1. Vital signs were monitored continuously by ECG, pulse oximetry (SpO2) and end-tidal respiratory and anaesthetic gas analysis. Oesophageal temperature was monitored and maintained within the range 38–39°C by use of a circulating warm-water blanket and forced air warming unit (Bair Hugger® Model 505, Arizant Health Care, MN, USA). Systolic pressure was measured using a Doppler probe placed over a digital artery and an occluding cuff and sphygmomanometer on the antebrachium. Respiratory gases were sampled from the level of the mid trachea via a 1 mm outer-diameter catheter passed down the orotracheal tube lumen. End-tidal gas samples were hand collected in a glass syringe in triplicate for each change in anaesthetic concentration. Gases were analysed by Raman spectrometry (Rascal® II, Ohmeda, UT, USA). For each agent the analyser was calibrated with at least three gas standards and calibration curves calculated. Measured anaesthetic concentrations were then mathematically corrected according to these calibration curves. MAC was determined in triplicate using standard tail-clamp technique. Data were analysed by two-way blocked ANOVA followed by Tukey test when significant differences were found. Values for individual MACs were also normalized to each agent’s mean value and correlation between agents evaluated.

Mean MAC values for isoflurane, sevoflurane and desflurane were 1.90 (SD 0.18), 3.41 (0.65) and 10.27 (1.06)%. Oesophageal temperatures, systolic pressures and SpO2 values recorded at the time of MAC determination for isoflurane, sevoflurane and desflurane were 38.3 (0.3), 38.6 (0.1) and 38.3 (0.3)°C; 71.2 (8.3), 74.6 (15.9) and 88.0 (12.0) mmHg; 99.2 (1.1), 99.1 (1.3) and 99.4 (0.8)%, respectively. The anaesthetic agent and the individual cat had significant effects on MAC values (P=0.0001 and P=0.0185, respectively). Rank order of an individual’s MAC values was similar for the three anaesthetic agents (Fig. 1). The correlation coefficients for isoflurane and sevoflurane, isoflurane and desflurane, and sevoflurane and desflurane were 0.97, 0.90 and 0.89, respectively. No correlation was found between age of cat and MAC for any agent.



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Fig 1 Isoflurane, sevoflurane and desflurane MAC values for six cats displaying consistent rank order.

 

    Comments
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
In this study individual cats had a significant effect on MAC values and these cats displayed a consistent order of sensitivity to isoflurane, sevoflurane and desflurane.

Each cat was anaesthetized with one agent at a time. However, for each agent, the order in which individual cats were anaesthetized was random. Lack of randomization of the inhaled agents may have affected MAC values for each agent for reasons such as variations in age or day length.5 Such factors should not, however, have consistently influenced the order of susceptibility of the cats to different agents.

Body temperature, oxygenation and systemic pressure have been shown to affect inhaled anaesthetic requirements.1 Cats in this study were normothermic at all times and not considered hypoxaemic based on SpO2 values of at least 95% at all times. Systolic pressure of cats in these studies averaged 77.9 mmHg over all MAC determination points. This may be considered to represent mild hypotension. No experimental studies have investigated the effects of hypotension on inhaled anaesthetic requirements in the cat. In dogs, reducing mean arterial pressure to 40–50 mmHg reduced halothane MAC by 20%.6

In the cat, the MAC of isoflurane has been reported to be 1.28–2.06%; that for sevoflurane 2.58% and desflurane 9.79%.710 Our reported MAC values for isoflurane, sevoflurane and desflurane are 1.90%, 3.41% and 10.27%, respectively. Variation in MAC may result from differences in laboratory technique but the findings of our study suggest that individual variation should also be considered as a contributory factor. This is consistent with current literature suggesting a genetic basis for variations in anaesthetic requirements.24 The genetic background of the cats in this study is not known, other than they were not direct litter mates. The consistent degree of sensitivity to isoflurane, sevoflurane and desflurane displayed by these cats lends support to the hypothesis that these three agents have a similar mechanism of action.


    Acknowledgements
 
This project was supported in part by grants received from the Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis.


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
1 Quasha AL, Eger EI II, Tinker JH. Determination and applications of MAC. Anesthesiology 1980; 53: 315–34[ISI][Medline]

2 Koblin DD, Dong DE, Deady JE, Eger EI II. Selective breeding alters murine resistance to nitrous oxide without alteration in synaptic membrane lipid composition. Anesthesiology 1980; 42: 401–7

3 Koblin DD, Deady JE, Eger EI II. Potency of inhaled anesthetics and alcohol in mice selectively bred for resistance and susceptibility to nitrous oxide anesthesia. Anesthesiology 1982; 56: 18–24[ISI][Medline]

4 Sonner JM, Gong D, Li J, et al. Mouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds. Anesth Analg 1999; 89: 1030–4[Abstract/Free Full Text]

5 Eger EI II, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 1965; 26: 756–63[ISI][Medline]

6 Tanifuji Y, Eger EI. Effect of arterial hypotension on anaesthetic requirement in dogs. Br J Anaesth 1976; 48: 947–51[Abstract]

7 Ilkiw JE, Pascoe PJ, Fisher LD. Effect of alfentanil on the minimum alveolar concentration of isoflurane in cats. Am J Vet Res 1997; 58: 1274–9[ISI][Medline]

8 Imai A, Ilkiw JE, Pypendop BH, Farver TB, Steffey EP. Nitrous oxide does not consistently reduce isoflurane requirements in cats. Vet Anaes Anal 2002; 29: 97–112[ISI]

9 Doi M, Yunoki H, Ikeda K. The minimum alveolar concentration of sevoflurane in cats. J Anesth 1988; 2: 113–14

10 McMurphy RM, Hodgson DS. The minimum alveolar concentration of desflurane in cats. Vet Surg 1995; 24: 453–5[ISI][Medline]





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