• 1

    Bailey PL, Egan TD, Stanley TH. Intravenous opioid anesthetics. In:Miller RD, ed.Anesthesia. 5th ed.Philadelphia: Churchill Livingstone Inc, 2000;273376.

    • Search Google Scholar
    • Export Citation
  • 2

    Jones RS. Epidural analgesia in the dog and cat. Vet J 2001;161:123131.

  • 3

    Bowdle TA. Adverse effects of opioid agonists and agonistantagonists in anaesthesia. Drug Saf 1998;19:173189.

  • 4

    Morgan M. Epidural and intrathecal opioids. Anaesth Intensive Care 1987;15:6067.

  • 5

    Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 1984;61:276310.

  • 6

    Herperger LJ. Postoperative urinary retention in a dog following morphine with bupivacaine epidural analgesia. Can Vet J 1998;39:650652.

    • Search Google Scholar
    • Export Citation
  • 7

    Tigerstedt I, Tammisto T. Double-blind, multiple-dose comparison of buprenorphine and morphine in postoperative pain. Acta Anaesthesiol Scand 1980;24:462468.

    • Search Google Scholar
    • Export Citation
  • 8

    Chrubasik J, Vogel W & Trotschler H, et al. Continuous-pluson-demand epidural infusion of buprenorphine versus morphine in postoperative treatment of pain. Postoperative epidural infusion of buprenorphine. Arzneimittelforschung 1987;37:361363.

    • Search Google Scholar
    • Export Citation
  • 9

    Wolff J, Carl P, Crawford ME. Epidural buprenorphine for postoperative analgesia. A controlled comparison with epidural morphine. Anaesthesia 1986;41:7679.

    • Search Google Scholar
    • Export Citation
  • 10

    Govindarajan R, Bakalova T & Michael R, et al. Epidural buprenorphine in management of pain in multiple rib fractures. Acta Anaesthesiol Scand 2002;46:660665.

    • Search Google Scholar
    • Export Citation
  • 11

    Valverde A, Dyson DH, McDonell WN. Epidural morphine reduces halothane MAC in the dog. Can J Anaesth 1989;36:629632.

  • 12

    Schwieger IM, Klopfenstein CE, Forster A. Epidural morphine reduces halothane MAC in humans. Can J Anaesth 1992;39:911914.

  • 13

    Golder FJ, Pascoe PJ & Bailey CS, et al. The effects of epidural morphine on the minimum alveolar concentration of isoflurane in cats. J Vet Anaesth 1998;25:5256.

    • Search Google Scholar
    • Export Citation
  • 14

    Miwa Y, Yonemura E, Fukushima K. Epidural administered buprenorphine in the perioperative period. Can J Anaesth 1996;43:907913.

  • 15

    Inagaki Y, Kuzukawa A. Effects of epidural and intravenous buprenorphine on halothane minimum alveolar anesthetic concentration and hemodynamic responses. Anesth Analg 1997;84:100105.

    • Search Google Scholar
    • Export Citation
  • 16

    Pypendop BH, Ilkiw JE & Imai A, et al. Hemodynamic effects of nitrous oxide in isoflurane-anesthetized cats. Am J Vet Res 2003;64:273278.

  • 17

    Pypendop BH, Ilkiw JE. The effects of intravenous lidocaine administration on the minimum alveolar concentration of isoflurane in cats. Anesth Analg 2005;100:97101.

    • Search Google Scholar
    • Export Citation
  • 18

    Kashyap L, Pawar DK & Kaul HL, et al. Effect of epidural morphine on minimum alveolar concentration of isoflurane in humans. J Postgrad Med 2003;49:211213.

    • Search Google Scholar
    • Export Citation
  • 19

    Nishimi Y. Comparative study of epidurally administered clonidine and buprenorphine on anesthetic requirement and electroencephalographic activity. Keio J Med 1996;45:324331.

    • Search Google Scholar
    • Export Citation
  • 20

    Troncy E, Cuvelliez SG, Blais D. Evaluation of analgesia and cardiorespiratory effects of epidurally administered butorphanol in isoflurane-anesthetized dogs. Am J Vet Res 1996;57:14781482.

    • Search Google Scholar
    • Export Citation
  • 21

    Inagaki Y, Mashimo T, Yoshiya I. Segmental analgesic effect and reduction of halothane MAC from epidural fentanyl in humans. Anesth Analg 1992;74:856864.

    • Search Google Scholar
    • Export Citation
  • 22

    Doherty TJ, Geiser DR, Rohrbach BW. Effect of high volume epidural morphine, ketamine and butorphanol on halothane minimum alveolar concentration in ponies. Equine Vet J 1997;29:370373.

    • Search Google Scholar
    • Export Citation
  • 23

    Ilkiw JE, Pascoe PJ, Fisher LD. Effect of alfentanil on the minimum alveolar concentration of isoflurane in cats. Am J Vet Res 1997;58:12741279.

    • Search Google Scholar
    • Export Citation
  • 24

    McEwan AI, Smith C & Dyar O, et al. Isoflurane minimum alveolar concentration reduction by fentanyl. Anesthesiology 1993;78:864869.

  • 25

    Hecker BR, Lake CL & DiFazio CA, et al. The decrease of the minimum alveolar anesthetic concentration produced by sufentanil in rats. Anesth Analg 1983;62:987990.

    • Search Google Scholar
    • Export Citation
  • 26

    Hall RI, Szlam F & Hug CC Jr. The enflurane-sparing effect of alfentanil in dogs. Anesth Analg 1987;66:12871291.

  • 27

    Quasha AL, Eger EI II, Tinker JH. Determination and applications of MAC. Anesthesiology 1980;53:315334.

  • 28

    Barter LS, Ilkiw JE & Steffey EP, et al. Animal dependence of inhaled anaesthetic requirements in cats. Br J Anaesth 2004;92:275277.

  • 29

    Attia J, Ecoffey C & Sandouk P, et al. Epidural morphine in children: pharmacokinetics and CO2 sensitivity. Anesthesiology 1986;65:590594.

  • 30

    Willer JC, Bergeret S, Gaudy JH. Epidural morphine strongly depresses nociceptive flexion reflexes in patients with postoperative pain. Anesthesiology 1985;63:675680.

    • Search Google Scholar
    • Export Citation
  • 31

    Thompson WR, Smith PT & Hirst M, et al. Regional analgesic effect of epidural morphine in volunteers. Can Anaesth Soc J 1981;28:530536.

  • 32

    Durant PA, Yaksh TL. Epidural injections of bupivacaine, morphine, fentanyl, lofentanil, and DADL in chronically implanted rats: a pharmacologic and pathologic study. Anesthesiology 1986;64:4353.

    • Search Google Scholar
    • Export Citation
  • 33

    Evron S, Sessler D & Sadan O, et al. Identification of the epidural space: loss of resistance with air, lidocaine, or the combination of air and lidocaine. Anesth Analg 2004;99:245250.

    • Search Google Scholar
    • Export Citation
  • 34

    Norman D. Epidural analgesia using loss of resistance with air versus saline: does it make a difference? Should we reevaluate our practice? AANA J 2003;71:449453.

    • Search Google Scholar
    • Export Citation
  • 35

    de Filho GR, Gomes HP & da Fonseca MH, et al. Predictors of successful neuraxial block: a prospective study. Eur J Anaesthesiol 2002;19:447451.

  • 36

    Beilin Y, Arnold I & Telfeyan C, et al. Quality of analgesia when air versus saline is used for identification of the epidural space in the parturient. Reg Anesth Pain Med 2000;25:596599.

    • Search Google Scholar
    • Export Citation
  • 37

    Sarna MC, Smith I, James JM. Paraesthesia with lumbar epidural catheters. A comparison of air and saline in a loss-of-resistance technique. Anaesthesia 1990;45:10771079.

    • Search Google Scholar
    • Export Citation
  • 38

    Roelants F, Veyckemans F & Van Obbergh L, et al. Loss of resistance to saline with a bubble of air to identify the epidural space in infants and children: a prospective study. Anesth Analg 2000;90:5961.

    • Search Google Scholar
    • Export Citation

Advertisement

Effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats

Bruno H. Pypendop DrMedVet, DrVetSci1, Peter J. Pascoe BVSc2, and Jan E. Ilkiw BVSc, PhD3
View More View Less
  • 1 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.
  • | 2 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.
  • | 3 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

Abstract

Objective—To determine effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats.

Animals—6 healthy adult domestic shorthair cats.

Procedures—Cats were anesthetized with isoflurane in oxygen. Morphine (100 μg/kg diluted with saline [0.9% NaCl] solution to a volume of 0.3 mL/kg), buprenorphine (12.5 μg/kg diluted with saline solution to a volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. The minimum alveolar concentration (MAC) of isoflurane was measured in triplicate by use of the tail clamp technique. At least 1 week was allowed between successive experiments.

Results—The MAC of isoflurane was 2.00 ± 0.18%, 2.13 ± 0.11%, and 2.03 ± 0.09% in the morphine, buprenorphine, and saline solution groups, respectively. No significant difference in MAC was detected among treatment groups.

Conclusions and Clinical Relevance—A significant effect of epidural administration of morphine or buprenorphine on the MAC of isoflurane in cats could not be detected. Further studies are needed to establish whether epidural opioid administration has other benefits when administered as a component of general anesthesia in cats.

Balanced anesthesia is defined as the concurrent administration of several anesthetic drugs so that no single drug is given in a dosage sufficient to induce toxicosis during or after surgery.1 Balanced anesthesia is often advocated to decrease the requirements for inhalant anesthetics and, thereby, limit the cardiovascular depression they induce. Epidural administration of drugs can be used as part of balanced anesthetic techniques and is widely used in dogs and cats to induce analgesia and reduce the requirements for inhalant anesthetics.2 Drugs that are most commonly administered by that route include opioids and local anesthetics.

The reported benefits of epidural administration of opioids include long duration, potent analgesia, a low required dose, and an expected low prevalence of adverse effects.2 Duration of action of epidural drugs is largely dependent on their lipid solubility. Morphine has been most widely used because of its favorable physicochemical characteristics (including low lipid solubility), wide availability, and low cost. In humans, epidural administration of morphine has been associated with vomiting, pruritus, and urinary retention.3–5 Although prevalence of vomiting and pruritus after epidural administration of morphine appears to be low in small animal patients, urinary retention has been anecdotally reported.6 This effect may last several days and may be detrimental to certain patients such as those undergoing a surgical procedure involving the urinary tract.

Buprenorphine, a partial opioid agonist, is approximately 33 times as potent as morphine when administered systemically.7 In humans, the analgesic potency of epidurally administered buprenorphine versus morphine was compared, revealing a potency ratio of 8:1.8 In humans, buprenorphine causes less urinary retention than does morphine.9,10 Although buprenorphine is used clinically in cats by systemic and epidural routes, its effects after epidural administration are poorly characterized in that species.

Epidural administration of morphine decreases the requirements for inhalant anesthetics in different species,11,12 and a 31% decrease in the MAC of isoflurane has been reported in cats.13 Epidural administration of buprenorphine decreases the MAC of halothane by 32% to 49% in humans.14,15 However, to our knowledge, no data on the effects of buprenorphine on inhalant MAC are available in cats.

The purpose of the study reported here was to compare the effects of epidural administration of morphine, buprenorphine, and saline (0.9% NaCl) solution on the MAC of isoflurane in cats. We hypothesized that morphine and buprenorphine, compared with saline solution, would significantly and similarly decrease MAC.

Materials and Methods

Cats—Six healthy adult female spayed domestic short-hair cats (mean ± SD weight, 5.4 ± 1.3 kg) were used in the study. Food was withheld from cats for 12 hours before the experiments were initiated. At least 1 week was allowed between successive experiments. The study was approved by the Institutional Animal Care and Use Committee at the University of California, Davis.

Instrumentation and monitoring—Anesthesia was induced with isoflurane in oxygen by use of an induction box and a face mask. The trachea was intubated with a cuffed endotracheal tube, and anesthesia was maintained with isoflurane in oxygen via a Bain circuit with a fresh-gas flow rate of 500 mL/kg/min. The cats were allowed to breathe spontaneously throughout the study. A catheter was passed through the lumen of the endotracheal tube so that its tip was positioned at the end of the tube. This catheter was connected to a Raman spectrometera for continuous measurement of inspired and end-tidal oxygen, carbon dioxide, and isoflurane concentrations. A 22-gauge, 2.5-cm catheter was inserted in a cephalic vein, and lactated Ringer's solution was administered at 3 mL/kg/h. A Doppler crystalb and occluding cuff were placed over a median artery for systolic blood pressure determination. A pulse oximetera probe was placed on the tongue, a foot, or an ear for measurement of SpO2 and pulse rate. A thermistorc calibrated prior to each experiment against a certified thermometer was placed in the esophagus at the level of the midthorax and connected to a physiographd and acquisition softwaree for continuous temperature monitoring. External heat (warm water, forced-air blankets, or both) was supplied as needed to maintain body temperature from 38.5° to 39.5°C.

Epidural drug administration—Cats were placed in sternal recumbency. After clipping and aseptic preparation of the lumbosacral area, a 22-gauge, 3.75-cm diamond point spinal needlef was inserted into the epidural space at the level of the lumbosacral junction. Epidural needle placement was confirmed by the absence of CSF (free flowing and after aspiration) and by the loss-of-resistance technique with a glass syringe and 1 mL of air. Correct placement was further confirmed by use of computed tomography, which revealed air (used for the loss-of-resistance technique) in the epidural space. After confirmation that the tip of the needle was in the epidural space, morphine (100 μg/kg diluted with saline solution to a volume of 0.3 mL/kg), buprenorphine (12.5 μg/kg diluted with saline solution to a volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered over 30 seconds, according to a Latin square design. In addition, epidural administration of morphine was repeated with the same dose and dilution after completion of the administrations via the Latin square. For this additional experiment, epidural needle placement was confirmed by the absence of CSF and the loss-of-resistance technique, by use of a glass syringe containing the solution to be administered. Before injection of the liquid, a small amount of air was introduced into the syringe and this was observed during injection for any signs of compression. Lack of change in volume of the bubble of air during injection was interpreted as indicating correct placement. No air was injected (ie, the injection was stopped before the air reached the needle); and therefore, computed tomography was not performed.

MAC—Cats were placed in right lateral recumbency. One hour was allowed after epidural administration before the first MAC determination. For each MAC determination, end-tidal isoflurane concentration was kept constant for at least 15 minutes. Pulse rate, esophageal temperature, systolic blood pressure, and SpO2 were recorded. End-tidal gas samples (5 mL) were obtained by manual collection in a glass syringe during 3 to 12 breaths. End-tidal isoflurane concentration was determined in these samples with an infrared analyzerg calibrated prior to each experiment with 3 calibration gasesh of known concentrations (isoflurane at 0.5%, 1.5%, and 2.5%). These samples were collected in triplicate, and the mean values were determined. A 20-cm Martin forceps was positioned on the tail and closed to the first ratchet until gross purposeful movement was observed or 1 minute had elapsed, whichever occurred first. Subsequent tail clampings were performed on slightly different areas of the tail (by moving the clamp a few millimeters proximally each time) to avoid tissue trauma. Isoflurane concentration was increased or decreased by 10% after a positive (gross purposeful movement) or negative response to tail clamping, respectively. The new concentration was kept constant for at least 15 minutes, and the measurements were repeated. Isoflurane MAC was defined as the mean of 2 successive isoflurane concentrations, 1 allowing and 1 preventing gross purposeful movement in response to tail clamping. The MAC was determined in triplicate, and the mean value was reported. At the end of the study, instruments were removed, and the cats were allowed to recover under observation.

Statistical analysis—Results of prospective power analysis based on previous MAC studies16,17 in cats conducted in our laboratory revealed that a sample size of 6 cats/ treatment group was required to detect a 20% difference in MAC between morphine and saline solution groups and between buprenorphine and saline solution groups, with a power of 0.8 and a significance level of P < 0.05. The MAC values in the 3 Latin square treatment groups were analyzed with a repeated-measures ANOVA. The MAC values from the additional morphine administration were compared with the MAC values in the morphine and saline solution groups from the Latin square design by use of repeated-measures ANOVA. Significance was set at P < 0.05. Data are presented as mean ± SD.

Results

Values obtained for all cats at all measurement times indicated that pulse rate, end-tidal PCO2, systolic arterial pressure, SpO2, and esophageal temperature were 165 ± 25 beats/min, 34.9 ± 6.1 mm Hg, 98 ± 17 mm Hg, 100 ± 0.1%, and 39.1 ± 0.3°C, respectively.

Cerebrospinal fluid was observed after placement of the spinal needle on 2 occasions. Because both cats were scheduled to receive saline solution, the procedure was not canceled. The needle was withdrawn into the epidural space, placement was confirmed by the loss-of-resistance technique and computed tomography, and the injection was performed.

The MAC of isoflurane was 2.00 ± 0.18%, 2.13 ± 0.11%, and 2.03 ± 0.09% in the Latin square morphine, buprenorphine, and saline solution groups, respectively. No significant difference in MAC was detected among treatment groups. In the morphine group, 1 cat had a 19% decrease and 1 cat a 12% increase in MAC, compared with their saline solution control values. In the buprenorphine group, 1 cat had a 14% increase and 1 cat a 17% increase in MAC, compared with their saline solution control values. All other changes in MAC were ≤ 10%, compared with the corresponding saline solution control values. The MAC of isoflurane in the additional morphine group was 1.93 ± 0.08% and was not significantly different from the MAC values in the Latin square morphine and saline solution groups. Compared with the saline solution control, 1 cat had a 14% decrease in MAC. This was the same cat that had a 19% decrease with the morphine treatment in the Latin square design. All other changes in MAC were ≤ 10%, compared with the corresponding saline solution control. No adverse effects were observed during recovery.

Discussion

In the study reported here, a significant effect on the MAC of isoflurane was not detected for morphine or buprenorphine administered into the epidural space. Although no data on the effects of epidural administration of buprenorphine on inhalant MAC are available in cats, the results reported here for morphine are in conflict with those of a previous study.13

This lack of MAC reduction with either opioid was unexpected. Opioids administered into the epidural space decrease anesthetic requirements in many species.5,11,12,14,15,18-22 The dose of morphine was selected on the basis of its wide clinical use and its effect on MAC in previous studies11,13 in dogs and cats. The dose of buprenorphine was selected in an attempt to administer equipotent doses of both opioids; results of a study8 in humans indicate an epidural potency ratio of 8:1 for buprenorphine and morphine.

Cats may be less responsive than other species to the effect of opioids on MAC. Maximal MAC reduction with systemic opioids in cats is 35%, compared with 73% in dogs, 100% in rats, and 82% in humans.23–26 Factors unrelated to drug administration may modify the MAC of inhalants and may account for failure to detect a treatment effect. Such factors include changes in body temperature, severe hypotension, severe hypoxemia, and severe hypercapnia.27 It is unlikely that these factors played a role in the study reported here. Body temperature was tightly controlled within 1°C by providing external heat as needed. Although mild hypotension was evident in some cats, severe hypotension was not detected at any time in this study. Inspired gas contained a high fraction of oxygen; this is expected to result in high PaO2. Although PaO2 was not measured, hypoxemia could be excluded on the basis of the high SpO2 observed in all cats throughout the study. Finally, PaCO2 was most likely in reference range in these cats, as indicated by the end-tidal PCO2 value that was in reference range. Alternatively, an apparent lack of drug effect could be apparent if the epidural administration of saline solution resulted in a reduction in MAC of similar magnitude to that caused by the drugs. This was deemed unlikely because the MAC of isoflurane in the epidural saline solution group was similar to MAC values in cats measured recently in our laboratory with identical methods.17,28 For similar reasons, we do not believe that the penetration of the subarachnoid space on 2 occasions in the saline solution group influenced the results. Lastly, it is possible that we performed the MAC measurements before the onset of drug effect. Onset of analgesic effect in humans has been repeatedly reported to be approximately 30 minutes after epidural morphine administration, with a peak effect at approximately 50 to 90 minutes.29–31 The effect on MAC might, however, be independent of the analgesic effect and, therefore, have a different onset time. From published studies11,12,22 that revealed an effect of morphine on MAC and in which onset can be assessed, it appears that onset occurred 30 to 100 minutes after administration. Specifically in cats, the time to onset in a previous study13 was 30 to 60 minutes. The onset of the effects of buprenorphine on MAC appears to be similar.15,19 We allowed 60 minutes for the onset of the effects of opioids on MAC. Additionally, we measured MAC in triplicate, and the last determination was completed at least 2.5 hours after epidural injection. No significant decrease in MAC was observed among successive measurements, suggesting that if onset was a factor in the study reported here, it was likely delayed by > 150 minutes.

Reasons for the lack of significant effect of epidural administration of morphine on MAC in the study reported here, compared with a 31% decrease reported with the same dose of morphine, are unclear.13 The MAC was determined in triplicate by tail clamping in both the study reported here and a previous study.13 However, several methodologic differences exist between these studies. Golder et al13 implanted vascular access devices in the epidural space. The effects of long-term catheter implantation on drug distribution and effect are unknown; in a study32 in rats, drug effects decreased 10 days after catheter implantation. This was hypothesized to be caused by a complete fibrous sheath surrounding the catheter. It is therefore unlikely that long-term catheter implantation would result in an increased effect. In the Golder et al13 study, the tip of the catheter was advanced to the junction between the sixth and seventh lumbar vertebrae, and drugs were therefore injected 1 vertebral length more cranially than in the present study. Drugs were also diluted to a volume of 0.2 mL/kg. Although the higher concentration of drug that resulted from this smaller dilution may have influenced the effect, a 21% MAC reduction was detected with 0.05 mg/kg diluted to a volume of 0.2 mL/kg, a larger dilution than in the study reported here. In addition, the larger volume used in our study is likely to have compensated for the more caudally placed injection. Golder et al13 maintained a slightly lower body temperature; however, the range of variation was similar to that in the study reported here, and changes in body temperature are more important in terms of detecting changes in MAC than the actual temperature (within the physiologic range). In the Golder et al13 study, the control and treatment MACs were measured during the same experiment, whereas they were measured during separate experiments in the study reported here. It is therefore possible that the effects of opioids on MAC are best detected after the CNS has been sensitized to noxious stimulation; however, to the authors' knowledge, this has not been reported. Interestingly, in the studies11,22 in dogs and horses that revealed a significant effect of morphine on MAC, the control MAC was also determined before the treatment MAC, during the same experiment. It could therefore be argued that the effect detected in those studies was related to time rather than to treatment; the lack of randomization of control versus treatment MAC determination prevents the statistical differentiation between time and treatment effects. This is, however, unlikely because MAC is considered to be insensitive to the duration of anesthesia.27 The most important difference between the Golder et al13 study and the study reported here may be the injection of air to confirm epidural needle placement in the latter study. Up to 2 mL of air is commonly injected into the epidural space as part of the loss-of-resistance technique.2 A 1-mL air injection was used in the study reported here to confirm the placement of the epidural needle (both for the loss-of-resistance technique and as contrast material for computed tomography). Although a smaller volume could have been used, the technique and volume were thought to be representative of clinical practice. The effects of air injection on quality of epidural analgesia are controversial, with results of some studies suggesting a detrimental effect, whereas others did not detect any effect.33–37 For those reporting a detrimental effect, a decrease in the quality of nerve block occurred in approximately 7% to 17% of patients. It is possible that air injection in the study reported here interfered with the effects of the epidural drugs. One cat in the morphine group had a 19% decrease in MAC, suggesting that if air injection decreased the effect of epidural morphine, it did so in 83% of the cats. Assuming that the loss-of-resistance technique with air abolishes the effect of epidural opioids, the exact prevalence obviously cannot be calculated from as small a sample as used in the study reported here; however, the prevalence would appear to be much higher than that reported in humans. Additionally, air injection cannot be used to explain the increase in MAC observed in 1 cat in the morphine group and 2 cats in the buprenorphine group.

In an attempt to determine whether air injection influenced the effect of epidural administration of morphine on MAC, administration of morphine was repeated without using air to confirm correct placement of the needle. Results of this additional experiment should be interpreted in view of 2 limitations: the order of epidural technique (ie, air injection vs no air injection) was not randomized, and correct needle placement could not be determined by use of computed tomography because of the lack of air administration. However, all epidural administrations were performed by the same experienced investigator (BHP), and correct needle placement was confirmed by use of the loss-of-resistance technique (without air), which is reliable in children and infants.38 Despite these limitations, the results suggest that injection of air was not involved in the lack of effect of morphine on isoflurane MAC. Interestingly, the only cat that had a decrease in MAC > 10% (ie, 19%) with morphine administration in the first experiment was also the only cat to have > 10% MAC reduction (ie, 14%) in the additional morphine group. This may suggest that in certain cats, epidural administration of morphine affects inhalant MAC, whereas in others, it does not and that this effect is consistent. Differences in MAC between the second morphine and saline solution administrations in all other cats were < 10%, which we believe cannot be interpreted because the bracketing method of MAC determination allows for a 10% difference between the anesthetic concentrations that determine MAC.

Despite the fact that in a number of species epidural administration of opioids can reduce MAC, it is often observed that the amount of inhalant needed during clinical surgery cannot be decreased. Because opioids are thought to have their main effect by hyperpolarizing afferent nociceptive neurons, it is possible that the suprathreshold stimulus used in this experiment was intense enough to overcome the hyperpolarization and cause the nociceptors to depolarize, thus explaining the lack of difference in MAC.

The potential consequences of performing 4 epidural injections at 1-week intervals on drug effect or distribution are not known. A Latin square design was used in an attempt to minimize a confounding effect of the treatment order. We consider it unlikely that a single epidural injection results in sufficient trauma to cause fibrosis or a modification of the distribution of the drugs. The last epidural injection was not more difficult to perform than the first. The distribution of air observed by use of computed tomography did not change among the first 3 experiments. However, this study was not terminal, and we could not determine whether there was gross or microscopic evidence of pathologic changes in the epidural space.

An effect of epidural administration of morphine or buprenorphine on the MAC of isoflurane in cats was not detected. Further studies are needed to assess whether epidural administration of these drugs in cats results in other beneficial effects.

ABBREVIATIONS

MAC

Minimum alveolar concentration

SpO2

Hemoglobin oxygen saturation

a.

Rascal II, Ohmeda, Salt Lake City, Utah.

b.

Model 811-B, Parks Medical, Aloha, Ore.

c.

YSI 701 temperature probe, Yellow Springs Instruments, Yellow Springs, Ohio.

d.

Gould Instrument Systems, Valley View, Ohio.

e.

Ponehma, version 4.20, LDS Life Science, Valley View, Ohio.

f.

Sherwood Medical, St Louis, Mo.

g.

Medical gas analyzer LB1, Beckman Instruments, Schiller Park, Ill.

h.

Isoflurane primary standard, Matheson Gas Products, Newark, Calif.

References

  • 1

    Bailey PL, Egan TD, Stanley TH. Intravenous opioid anesthetics. In:Miller RD, ed.Anesthesia. 5th ed.Philadelphia: Churchill Livingstone Inc, 2000;273376.

    • Search Google Scholar
    • Export Citation
  • 2

    Jones RS. Epidural analgesia in the dog and cat. Vet J 2001;161:123131.

  • 3

    Bowdle TA. Adverse effects of opioid agonists and agonistantagonists in anaesthesia. Drug Saf 1998;19:173189.

  • 4

    Morgan M. Epidural and intrathecal opioids. Anaesth Intensive Care 1987;15:6067.

  • 5

    Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 1984;61:276310.

  • 6

    Herperger LJ. Postoperative urinary retention in a dog following morphine with bupivacaine epidural analgesia. Can Vet J 1998;39:650652.

    • Search Google Scholar
    • Export Citation
  • 7

    Tigerstedt I, Tammisto T. Double-blind, multiple-dose comparison of buprenorphine and morphine in postoperative pain. Acta Anaesthesiol Scand 1980;24:462468.

    • Search Google Scholar
    • Export Citation
  • 8

    Chrubasik J, Vogel W & Trotschler H, et al. Continuous-pluson-demand epidural infusion of buprenorphine versus morphine in postoperative treatment of pain. Postoperative epidural infusion of buprenorphine. Arzneimittelforschung 1987;37:361363.

    • Search Google Scholar
    • Export Citation
  • 9

    Wolff J, Carl P, Crawford ME. Epidural buprenorphine for postoperative analgesia. A controlled comparison with epidural morphine. Anaesthesia 1986;41:7679.

    • Search Google Scholar
    • Export Citation
  • 10

    Govindarajan R, Bakalova T & Michael R, et al. Epidural buprenorphine in management of pain in multiple rib fractures. Acta Anaesthesiol Scand 2002;46:660665.

    • Search Google Scholar
    • Export Citation
  • 11

    Valverde A, Dyson DH, McDonell WN. Epidural morphine reduces halothane MAC in the dog. Can J Anaesth 1989;36:629632.

  • 12

    Schwieger IM, Klopfenstein CE, Forster A. Epidural morphine reduces halothane MAC in humans. Can J Anaesth 1992;39:911914.

  • 13

    Golder FJ, Pascoe PJ & Bailey CS, et al. The effects of epidural morphine on the minimum alveolar concentration of isoflurane in cats. J Vet Anaesth 1998;25:5256.

    • Search Google Scholar
    • Export Citation
  • 14

    Miwa Y, Yonemura E, Fukushima K. Epidural administered buprenorphine in the perioperative period. Can J Anaesth 1996;43:907913.

  • 15

    Inagaki Y, Kuzukawa A. Effects of epidural and intravenous buprenorphine on halothane minimum alveolar anesthetic concentration and hemodynamic responses. Anesth Analg 1997;84:100105.

    • Search Google Scholar
    • Export Citation
  • 16

    Pypendop BH, Ilkiw JE & Imai A, et al. Hemodynamic effects of nitrous oxide in isoflurane-anesthetized cats. Am J Vet Res 2003;64:273278.

  • 17

    Pypendop BH, Ilkiw JE. The effects of intravenous lidocaine administration on the minimum alveolar concentration of isoflurane in cats. Anesth Analg 2005;100:97101.

    • Search Google Scholar
    • Export Citation
  • 18

    Kashyap L, Pawar DK & Kaul HL, et al. Effect of epidural morphine on minimum alveolar concentration of isoflurane in humans. J Postgrad Med 2003;49:211213.

    • Search Google Scholar
    • Export Citation
  • 19

    Nishimi Y. Comparative study of epidurally administered clonidine and buprenorphine on anesthetic requirement and electroencephalographic activity. Keio J Med 1996;45:324331.

    • Search Google Scholar
    • Export Citation
  • 20

    Troncy E, Cuvelliez SG, Blais D. Evaluation of analgesia and cardiorespiratory effects of epidurally administered butorphanol in isoflurane-anesthetized dogs. Am J Vet Res 1996;57:14781482.

    • Search Google Scholar
    • Export Citation
  • 21

    Inagaki Y, Mashimo T, Yoshiya I. Segmental analgesic effect and reduction of halothane MAC from epidural fentanyl in humans. Anesth Analg 1992;74:856864.

    • Search Google Scholar
    • Export Citation
  • 22

    Doherty TJ, Geiser DR, Rohrbach BW. Effect of high volume epidural morphine, ketamine and butorphanol on halothane minimum alveolar concentration in ponies. Equine Vet J 1997;29:370373.

    • Search Google Scholar
    • Export Citation
  • 23

    Ilkiw JE, Pascoe PJ, Fisher LD. Effect of alfentanil on the minimum alveolar concentration of isoflurane in cats. Am J Vet Res 1997;58:12741279.

    • Search Google Scholar
    • Export Citation
  • 24

    McEwan AI, Smith C & Dyar O, et al. Isoflurane minimum alveolar concentration reduction by fentanyl. Anesthesiology 1993;78:864869.

  • 25

    Hecker BR, Lake CL & DiFazio CA, et al. The decrease of the minimum alveolar anesthetic concentration produced by sufentanil in rats. Anesth Analg 1983;62:987990.

    • Search Google Scholar
    • Export Citation
  • 26

    Hall RI, Szlam F & Hug CC Jr. The enflurane-sparing effect of alfentanil in dogs. Anesth Analg 1987;66:12871291.

  • 27

    Quasha AL, Eger EI II, Tinker JH. Determination and applications of MAC. Anesthesiology 1980;53:315334.

  • 28

    Barter LS, Ilkiw JE & Steffey EP, et al. Animal dependence of inhaled anaesthetic requirements in cats. Br J Anaesth 2004;92:275277.

  • 29

    Attia J, Ecoffey C & Sandouk P, et al. Epidural morphine in children: pharmacokinetics and CO2 sensitivity. Anesthesiology 1986;65:590594.

  • 30

    Willer JC, Bergeret S, Gaudy JH. Epidural morphine strongly depresses nociceptive flexion reflexes in patients with postoperative pain. Anesthesiology 1985;63:675680.

    • Search Google Scholar
    • Export Citation
  • 31

    Thompson WR, Smith PT & Hirst M, et al. Regional analgesic effect of epidural morphine in volunteers. Can Anaesth Soc J 1981;28:530536.

  • 32

    Durant PA, Yaksh TL. Epidural injections of bupivacaine, morphine, fentanyl, lofentanil, and DADL in chronically implanted rats: a pharmacologic and pathologic study. Anesthesiology 1986;64:4353.

    • Search Google Scholar
    • Export Citation
  • 33

    Evron S, Sessler D & Sadan O, et al. Identification of the epidural space: loss of resistance with air, lidocaine, or the combination of air and lidocaine. Anesth Analg 2004;99:245250.

    • Search Google Scholar
    • Export Citation
  • 34

    Norman D. Epidural analgesia using loss of resistance with air versus saline: does it make a difference? Should we reevaluate our practice? AANA J 2003;71:449453.

    • Search Google Scholar
    • Export Citation
  • 35

    de Filho GR, Gomes HP & da Fonseca MH, et al. Predictors of successful neuraxial block: a prospective study. Eur J Anaesthesiol 2002;19:447451.

  • 36

    Beilin Y, Arnold I & Telfeyan C, et al. Quality of analgesia when air versus saline is used for identification of the epidural space in the parturient. Reg Anesth Pain Med 2000;25:596599.

    • Search Google Scholar
    • Export Citation
  • 37

    Sarna MC, Smith I, James JM. Paraesthesia with lumbar epidural catheters. A comparison of air and saline in a loss-of-resistance technique. Anaesthesia 1990;45:10771079.

    • Search Google Scholar
    • Export Citation
  • 38

    Roelants F, Veyckemans F & Van Obbergh L, et al. Loss of resistance to saline with a bubble of air to identify the epidural space in infants and children: a prospective study. Anesth Analg 2000;90:5961.

    • Search Google Scholar
    • Export Citation

Contributor Notes

Supported by the Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis.

The authors thank Rich Larson for performing computed tomography studies and Kristine Siao for technical assistance.

Address correspondence to Dr. Pypendop.