Desflurane is a volatile inhalation anesthetic used in clinical and research settings. It possesses the lowest solubility index of all available inhalation anesthetics, allowing for rapid equilibration of anesthetic concentrations within the alveoli, bloodstream, and CNS. Low solubility facilitates faster control of the depth of anesthesia.1,2 The rapid response is attributable to changes in inspired concentration of the anesthetic agent as well as an increased rate at which the alveolar concentration of the anesthetic agent approaches the inspired concentration.1,3–5 Similar to other inhalation anesthetics, desflurane undergoes minimal hepatic and renal metabolism and causes a dose-dependent decrease in arterial blood pressure, systemic vascular resistance, cardiac output, and minute ventilation.2,4,6,7
The MAC of an inhalation anesthetic represents the concentration required to prevent gross purposeful movement in response to a supramaximal noxious stimulus in 50% of a population at a barometric pressure of 1 atm.8–11 For a given inhalation anesthetic, the alveolar concentration required to induce unresponsiveness to a supramaximal noxious stimulus in an individual animal is fairly consistent. Within animal species, < 20% variation in MAC can be expected among individuals, regardless of duration of anesthesia.12 This reproducibility is helpful when attempting to correlate dose of anesthetic agent and depth of anesthesia.7,8 Minimum alveolar concentration is used as a standard by which potencies of inhalation anesthetics are compared. Concurrent administration of other drugs can affect the degree to which the MAC of administered anesthetic agent can be reduced (ie, MAC-sparing effect).11 The primary purpose of MAC reduction is to ease cardiovascular and respiratory compromise associated with inhalation anesthetics.11,13
Opioids are known to have MAC-sparing effects in dogs, swine, and primates,14–16 but little information exists regarding the MAC-sparing effects of opioids in small ruminants. Although oxymorphone and hydromorphone are commonly used in small animal practice for their analgesic and MAC-sparing effects,14 their use in sheep has not been reported, to the authors’ knowledge. An inhalation anesthetic-sparing effect can be achieved with a constant rate IV infusion of fentanyl in sheep.17 Similarly, a dose-dependent reduction in MAC can be achieved with IV administration of fentanyl to healthy, mechanically ventilated goats.18 In dogs and primates, opioid administration results in intense MAC-sparing effects and analgesia.16 However, in other species, opioids may have limited MAC-sparing but good analgesic effects.16,17 Although opioids are not considered particularly effective analgesic agents for small ruminants, opioid administration can result in analgesia in response to thermal stimuli and have variable analgesic effects in response to mechanical noxious stimuli.19–21 Furthermore, intrathecal administration of hydromorphone is reportedly safe in sheep.22
The purpose of the study reported here was to determine MACdes, determine whether IV administration of oxymorphone hydrochloride or hydromorphone hydrocloride would have a MAC-sparing effect on desflurane, and evaluate the cardiovascular effects of desflurane in combination with oxymorphone or hydromorphone in nulliparous sheep. We hypothesized that the MACdes in sheep would be similar to that in other species and that oxymorphone and hydromorphone would have MAC-sparing effects similar to each other when administered IV during desflurane anesthesia.
Materials and Methods
Animals
Eight healthy adult nulliparous mixed-breed sheep with a mean body weight of 69.8 kg (range, 58 to 84 kg) were used in the study. All sheep were of appropriate body condition, dewormed, and determined to be in good health on the basis of results of physical examination, CBC, and serum biochemical analysis. Sheep were housed outdoors on pasture and brought into the test facility 24 hours prior to each anesthetic session. Food was withheld for 24 hours and water was withheld for 12 hours prior to induction of anesthesia. The Texas A&M University Institutional Animal Care and Use Committee approved the study protocol.
Experimental design
A randomized crossover study design was used. Randomization of treatment order was made with the aid of a randomized plan generator.a Each sheep was evaluated individually on 2 occasions (to allow assessment of the effects of each of 2 opioids) that were separated by a minimum of 10 days. Each sheep acted as its own control for baseline measurements (before MAC determination began, with ETdes maintained at 10%) and MAC determination.
Anesthetic protocol
For each sheep, anesthesia was induced with desfluraneb at 18% in 100% oxygen (4 L/min) and delivered through a circle anesthetic system by use of a tight-fitting mask. In preparation for orotracheal intubation, the arytenoid cartilage region was desensitized by topical application of 2% lidocaine solution.c Intubation was subsequently performed by use of a laryngoscope and cuffed endotracheal tube. Anesthesia was maintained with desflurane in 100% oxygen (20 mL/kg/min) by use of a small animal anesthetic machine with a rebreathing circuitd and electronic vaporizer.e An orogastric tube was inserted into each sheep to decrease the chance of bloating. Fluidsf were administered via introducer catheter into the right external jugular vein at a rate of 5 mL/kg/h. Each sheep breathed spontaneously while monitoring instruments were being applied, and manual intermittent positive pressure ventilation was initiated when hypercapnia developed (Petco2 > 50 mm Hg). Once instrumentation was completed, time-cycled, volume-controlled, intermittent positive-pressure ventilationg was instituted and normocapnia was maintained throughout anesthesia (Petco2, 35 to 45 mm Hg).
Instrumentation and monitoring
Each sheep was temporarily positioned in left lateral recumbency, and an 8F introducerh was inserted in the right external jugular vein. Sheep were then temporarily positioned in dorsal recumbency to facilitate secure placement of a pulmonary arterial catheter.i The distal port of the pulmonary arterial catheter was connected to a transducer attached to the data acquisition device.j As the catheter was advanced through the jugular vein, vena cava, right atrium, right ventricle, and pulmonary artery, characteristic pressure waveforms at each anatomic site were obtained and used to confirm the proper position of the catheter tip within the pulmonary artery.
Sheep were positioned in right lateral recumbency for the remainder of the anesthetic session. A 22-gauge catheterk was inserted in the medial branch of the left anterior auricular artery. The arterial catheter was connected to a 60-inch, fluid-filled, high-pressure tube that was attached to a transducer for direct monitoring of arterial blood pressures.1 The transducer was positioned at the level of the heart and zeroed prior to any direct measurements of blood pressure. The point of the shoulder joint was used as a reference for transducer positioning while sheep were in dorsal recumbency, and the middle of the sternum was used as a reference once sheep were in lateral recumbency. Before each anesthetic session, the blood pressure transducer system was calibrated and tested in accordance with the manufacturer's recommendations. Once the transducer was connected to the monitor and pressure gauge, a calibrated syringe full of air was used to produce specific pressure of 0, 100, 150, or 200 mm Hg, and the corresponding voltage detected by the transducer at each pressure was noted.
Inspired desflurane concentration and Petco2 were monitored continually with a side-stream gas analyzerm at a rate of 50 mL/min. The gas analyzer unit was calibrated at the start of each anesthetic session by use of calibration gases supplied by the manufacturer (5% CO2, 55% O2, 33% N2O, and 2% desflurane). Body temperature was monitored by use of an esophageal probe. Blankets were applied to sheep to maintain esophageal temperature within reference limits (38.2° to 39.5°C). Electrocardiographic patterns and Spo2 as measured with a lingual probe were continually monitored throughout each anesthetic session.
Cardiac output was measured by means of a thermodilution method at baseline and at MACdes and MACdes+opioid determination.23 Mechanical ventilation was stopped prior to measurement of cardiac output. For measurement, 10 mL of ice-cold 5% dextrose solutione was injected into the proximal port of the pulmonary arterial catheter during a 3-second period, and the cardiac output measurement curve was displayed in real time. A series of 3 measurements, which were required to be within 10% of each other, were made in rapid succession to obtain consistent results.
During each anesthetic session, just before measurement of cardiac output, an arterial blood sample (3 mL) was obtained from sheep at baseline and at MACdes and MACdes+opioid determination for measurement of blood gas and electrolyte concentrations, PCV, and blood total protein concentration. Throughout anesthesia and prior to the application of the noxious stimulus, values were monitored and recorded for heart rate, invasively measured arterial blood pressure, Petco2, Spo2, and esophageal temperature.
MAC determination
After induction of anesthesia and proper instrumentation of sheep, ETdes was maintained between 9.9% and 10.1% for at least 20 minutes and baseline measurements were obtained.23 To produce a supramaximal noxious stimulus for MAC determination, jaws of a vulsellum forcepsn were placed 1 cm below the coronary band of the left forelimb of each sheep and alternately clamped around the medial (digit 3) and lateral (digit 4) digit for each stimulus application. Jaws of the vulsellum forceps were closed tightly to the same degree each time as identified by a taped line on the jaws. Digits were clamped for a maximum of 1 minute or until gross purposeful movement (movement of the head and or any limb) was noticed. Coughing, swallowing, and chewing were not considered gross purposeful movement, and paddling or shaking was considered unrelated to noxious stimulus.5,12,18 When gross purposeful movement was detected, ETdes was increased in increments of 0.5% and maintained at the new concentration for 10 minutes to allow equilibration to occur prior to stimulus reapplication. This process was continued until a negative response was detected. Once no purposeful movement was evident and after the ETdes was increased, expired desflurane concentration was decreased by 0.2% and maintained for 10 minutes to allow for equilibration prior to stimulus reapplication each time. The same procedure was continued until purposeful movement was detected. When the original noxious stimulus did not produce gross purposeful movement, ETdes was adjusted in increments of the same magnitude as previously described, but in the opposite direction. The MACdes was defined as the mean of the highest concentration that resulted in gross purposeful movement and the lowest concentration that prevented movement and was determined in duplicate for each anesthetic session, with the mean of the means used in statistical analyses.
Drug administration and MACdes+opioid determination
After MACdes was determined, oxymorphone hydrochlorideo (0.05 mg/kg) or hydromorphone hydrochloridep (0.10 mg/kg) was administered IV during a 10-second period through the catheter in the right external jugular vein. Investigators were unaware of which drug was being administered. Drug doses had been extrapolated from equipotent doses established for dogs, given that doses of other opioids used in dogs such as fentanyl, butorphanol, morphine, and buprenorphine have been also used in sheep.15,17,24–26 Heart rate and arterial blood pressure were recorded prior to (0 minutes) and 5 and 10 minutes after opioid administration to allow assessment of the immediate cardiovascular effects of each drug. At 10 minutes after opioid administration, the described method for MACdes determination was repeated to determine MACdes+opioid for oxymorphone or hydromorphone in duplicate. The mean findings of duplicate tests were determined for statistical analyses.
Recovery from anesthesia
At the end of each anesthetic session, mechanical ventilation of sheep was stopped, the vaporizer was turned off, and sheep were positioned in sternal recumbency. The anesthetic breathing system was flushed with 100% oxygen. When sheep failed to breathe spontaneously within 1 minute after the vaporizer was turned off, breathing was manually assisted at a rate of 2 breaths/min until spontaneous breathing resumed. Once sheep began to swallow and lift their heads, the endotracheal tube was removed. Times when specific stages of anesthetic induction and recovery occurred were recorded. A published 3-point scoring system18 was used to evaluate quality of anesthetic recovery for each sheep as follows: 1 = restlessness observed, 2 = fairly smooth recovery with some restlessness observed, and 3 = smooth recovery with no restlessness observed.
Statistical analysis
Statistical analysis was performed by use of statistical software.q All values are reported as mean ± SEM. Repeated-measures 1-way ANOVA was used to identify differences among baseline, MACdes, and MACdes+opioid values for heart rate; systolic, diastolic, and mean arterial blood pressures; cardiac output; ETdes; hematologic values; and esophageal temperature. The Sidak method for post hoc hypothesis testing was also used. The same method of analysis was used to compare durations of the following variables: interval from induction of anesthesia to orotracheal intubation, interval from intubation to noxious stimulus application, intervals from orotracheal intubation to MACdes and MACdes+opioid determination, interval from MACdes determination to MACdes+opioid determination, total duration of anesthesia, and intervals from discontinuation of anesthesia to spontaneous breathing, extubation, sternal recumbency, and standing. Analysis of variance was also used to identify any effects of treatment on physiologic values, and the paired t test was used to identify any effects of treatment on MAC. Values of P < 0.05 were considered significant.
Results
MACdes and MACdes+opioid
Mean ± SEM MACdes for the 8 healthy sheep anesthetized in the study was 8.6 ± 0.2%. No difference was identified between MACdes measured after IV administration of oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg). At the doses used, opioid administration resulted in a significant decrease in MACdes (Table 1). Before application of the noxious stimulus, differences between alveolar and inspired concentrations of desflurane were maintained at < 0.2%. Three sheep moved spontaneously during MACdes and MACdes+opioid determination, but that movement was not attributable to stimulus application.
Mean ± SEM MACs and percentage change between MACs in 8 healthy nulliparous desflurane-anesthetized sheep before and after IV administration of oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg) in a crossover study.
| Drug | MACdes (%) | MACdes+opioid (%) | Change (%%)* |
|---|---|---|---|
| Hydromorphone | 8.6 ± 0.2 | 7.9 ± 0.2† | −7.6 |
| Oxymorphone | 8.7 ± 0.3 | 7.6 ± 0.4† | −12.4 |
Percentage change was calculated as [(MACdes − MACdes+opioid)/MACdes] × 100%.
Value differs significantly (P < 0.05) from the corresponding MACdes.
No significant difference was detected between hematologic values measured at MACdes determination versus MACdes+opioid determination (for oxymorphone or hydromorphone). All blood gas values, blood electrolyte and total protein concentrations, and PCVs were within reference limits. Normothermia and normocapnia were also maintained in all sheep.
Effects of MACdes and MACdes+opioid on cardiovascular variables
Heart rate and mean arterial blood pressure decreased 10 minutes after administration of either opioid, but this decrease was only significant for hydromorphone (data not shown). Arterial blood pressure, heart rate, and cardiac output values measured at MACdes and MACdes+opioid determinations were significantly greater than values measured at baseline (before MAC determination began, with ETdes maintained at 10%). There were no significant differences in cardiovascular values between MACdes and MACdes+opioid (Table 2).
Mean ± SEM cardiovascular values for the sheep in Table 1 at baseline, MACdes determination, and MACdes+opioid determination after IV administration of oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg).
| MACdes+opioid | ||||
|---|---|---|---|---|
| Variable | Baseline | MACdes | Oxymorphone | Hydromorphone |
| Heart rate (beats/min) | 93.8 ± 3.2 | 95.7 ± 5.3 | 103.3 ± 3.5* | 97.4 ± 3.2 |
| SAP (mm Hg) | 85.9 ± 2.5 | 101.3 ± 2.8* | 107.1 ± 4.4* | 102.0 ± 3.3* |
| MAP (mm Hg) | 70.8 ± 2.5 | 84.3 ± 2.4* | 88.7 ± 3.8* | 84.5 ± 2.9* |
| DAP (mm Hg) | 63.2 ± 2.5 | 77.3 ± 2.6* | 79.9 ± 3.7* | 75.9 ± 2.9* |
| Cardiac output (L/min) | 7.4 ± 0.3 | 8.9 ± 0.6 | 12.1 ± 1.3* | 10.7 ± 1.1* |
Value differs significantly (P < 0.05) from the corresponding baseline value.
DAP = Diastolic arterial blood pressure. MAP = Mean arterial blood pressure. SAP = Systolic arterial blood pressure.
Baseline measurements were made before MAC determination began, with ETdes maintained at 10%. Other measurements were made prior to opioid administration and 5 and 10 minutes after opioid administration.
Anesthetic induction and recovery times
Mean duration of anesthesia was 390 minutes. No significant difference was identified between oxymorphone and hydromorphone treatment with regard to duration of anesthesia or any other interval related to induction of anesthesia, MAC determination, and anesthetic recovery (Table 3). Induction of anesthesia was rapid and without complications, with a mean interval from induction of anesthesia to orotracheal intubation for both sessions of 11.6 ± 1.2 minutes. All sheep had a smooth and unremarkable recovery (score of 3). Overall mean interval from discontinuation of desflurane exposure to extubation was 4.4 ± 0.4 minutes, with the endotracheal tube removed from all sheep by 7 minutes after the vaporizer was turned off. Overall mean interval from discontinuation of desflurane exposure to standing was 19.5 ± 2.6 minutes.
Mean ± SEM duration (min) of various intervals during desflurane anesthesia for MACdes and MACdes+opioid determinations in the sheep in Tables 1 and 2 after IV administration of oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg).
| Interval | Oxymorphone | Hydromorphone |
|---|---|---|
| From induction of anesthesia to orotracheal intubation | 11.0 ± 1.6 | 12.0 ± 1.9 |
| From orotracheal intubation to first noxious stimulus | 83.0 ± 4.4 | 82.0 ± 3.6 |
| From orotracheal intubation to MACdes determination | 183.0 ± 14.0 | 197.0 ± 19.0 |
| From orotracheal intubation to MACdes+opioid determination | 324.0 ± 16.0 | 341.0 ± 21.0 |
| From MACdes to MACdes+opioid determination | 141.0 ± 13.0 | 142.0 ± 13.0 |
| Total duration of anesthesia | 374.0 ± 16.0 | 406.0 ± 20.0 |
| From discontinuation of desflurane administration to first spontaneous breath | 1.3 ± 0.3 | 0.8 ± 0.4 |
| From desflurane discontinuation to extubation | 4.8 ± 0.5 | 4.0 ± 0.7 |
| From desflurane discontinuation to sternal recumbency | 5.0 ± 0.7 | 5.3 ± 0.8 |
| From desflurane discontinuation to standing | 21.0 ± 3.7 | 18.0 ± 3.9 |
Differences between sheep when given oxymorphone or hydromorphone were not significant (ie, P ≥ 0.05).
Discussion
Anesthesia was tolerated well in the present study of the effects of desflurane, oxymorphone (0.05 mg/kg), and hydromorphone (0.10 mg/kg) in sheep, as has been reported for other animal species.9,13,24,27,q,r The MACdes in the mechanically ventilated, nulliparous sheep was established as 8.6 ± 0.2%. Given that MAC values can vary within the same animal by as much as 10%, the present findings were in agreement with those of a studyr in which MACdes in nonpregnant ewes was reported to be approximately 8% higher than our results. Potential confounding factors such as age, reproductive status, and experimental design may have contributed to this small difference between studies. The MACdes determined in the present study was consistent given that it was measured in duplicate on 2 occasions for the same sheep, and all MACdes values were similar. In another abstract,s the MACdes in pregnant ewes was reportedly 6.1%, which is approximately 29% less than the value in the present study and was likely attributable to the MAC-sparing effect of progesterone in pregnant mammals.28,r
The ETdes in the sheep of the study reported here was maintained for at least 10 minutes to allow for physiologic equilibration of desflurane concentration before MAC determination. The 10-minute period was derived from the number of time constants needed for equilibration of desflurane concentration within the brain. Given a cerebral blood flow rate of 50 mL/100 g of brain tissue/min and a brain-blood partition coefficient for desflurane of 1.3, 1 time constant for desflurane to equilibrate in brain tissue was calculated as 2.6 minutes. Each time constant allows for 63% equilibration; therefore, 1 time constant allows 63% of equilibration, 2 time constants allow 86% equilibration, and 3 time constants allow 95% equilibration.8,29 Therefore, 10 minutes allowed at least 95% equilibration of desflurane concentrations within the alveoli, bloodstream, and CNS in the sheep of the present study.8,29 The brain-blood partition coefficient has not been reported for sheep and was extrapolated from values reported for other species.29 Cerebral blood flow rate in conscious ewes is reportedly between 50 mL/100 g of brain tissue/min and 129 mL/100 g of brain tissue/min.30,31 Sheep anesthetized with halothane have a reported cerebral blood flow rate of 200 mL/100 g/min.32 Furthermore, desflurane reportedly maintains or increases cerebral blood flow in sheep and other species.33,34 The mean ± SD blood-gas partition coefficient for desflurane in sheep is 0.496 ± 0.056. This value is similar to the value reported for humans (0.498 ± 0.012), suggesting the brain-blood partition coefficient is similar between these species.34,35 Differences between inspired and alveolar concentrations of desflurane were maintained at < 0.25% in the present study, suggesting that equilibration occurred within 10 minutes.
The MAC-sparing effects of oxymorphone and hydromorphone on desflurane anesthesia in sheep were also evaluated in the study reported here. Intravenous administration of either opioid resulted in a significant decrease in MACdes, without compromising hemodynamic performance. In fact, after administration of either opioid, cardiac output increased from the values recorded at MACdes determination. In general, an increase in cardiac output can be attributed to an increase in either heart rate or stroke volume. We presumed that cardiac output increased because of an increase in stroke volume, potentially as a result of the decrease in desflurane concentration and consequent decrease in the negative inotropic effect of the drug. However, cardiovascular variables may have also been influenced by a potential response of the sympathetic nervous system to the noxious stimulus applied during MAC determination. Nevertheless, values recorded during MAC determination corresponded to values recorded before stimulus application and after > 10 minutes had elapsed following the previous stimulus.
The MAC-sparing effects of opioids used in the present study may be considered clinically minimal when compared with the reduction in MAC achieved after administration of the same opioids at the same doses in other species. Dogs anesthetized with isoflurane had a reduction in MAC of approximately 45% after administration of the same opioids in another study.11 In a study17 involving sheep that received an IV infusion of fentanyl at a rate commonly used in dogs, the MAC-sparing effect was approximately half that reported for dogs.14
Spontaneous locomotor activity such as head-shaking unassociated with the noxious stimulus was detected at various stages of the present study, and its incidence was higher after opioid administration. We were unable to identify a reason for this activity; however, body shaking has been noticed clinically in anesthetized small ruminants regardless of anesthetic depth. For example, spontaneous muscle movement in ruminants is reportedly common when opioid-based anesthetic protocols are used.36
Significant decreases in heart rate and arterial blood pressure were identified 5 and 10 minutes after hydromorphone administration to sheep in the present study (data not shown), whereas oxymorphone administration resulted in a similar but nonsignificant decrease. Opioid administration has been associated with an increase in vagal tone, which may lead to a decrease in heart rate and impact on cardiac output.37 These effects, along with the negative inotropic effect of desflurane, might have been responsible for the decrease in blood pressure observed 10 minutes after opioid administration.6 In other species, histamine-induced systemic vasodilation can occur after IV administration of hydromorphone.38 However, cardiovascular effects in the present study were short-lived. In fact, hemodynamic performance in the sheep of the present study was maintained once MACdes+opioid was reached for both oxymorphone and hydromorphone, as suggested by the increase in cardiac output and blood pressure at the moment of MACdes+opioid determination. This finding is in agreement with results of other studies39,t in which the use of a balanced anesthetic technique was beneficial because patients were more hemodynamically stable.
The short anesthetic induction and recovery periods in the study reported here were in agreement with findings of other studies40,41 in which the effects of desflurane anesthesia in sheep were evaluated. After both anesthetic sessions (one with oxymorphone and the other with hydromorphone), each sheep had a smooth and rapid recovery. All sheep resumed spontaneous breathing within 2 minutes, and extubation was performed within 7 minutes after discontinuation of desflurane exposure. This rapid recovery was attributed to the low blood-gas partition coefficient of desflurane, which was presumed to have led to fast changes in anesthetic concentrations within the CNS, bloodstream, and alveoli, thereby allowing a fast redistribution of anesthetic agent from the CNS.6,28 In rats, the rate of recovery from desflurane anesthesia is 2 times that with sevoflurane, 3 to 5 times that with isoflurane, and 5 to 10 times that with halothane.42 In human medicine, anesthesia maintained with desflurane has been compared with anesthesia maintained with sevoflurane, isoflurane, halothane, and propofol, revealing a more rapid awakening with desflurane than with the other inhalation anesthetics.43 Overall mean interval from discontinuation of desflurane anesthesia to extubation in the study reported here was 4 minutes, and all sheep had a smooth anesthetic recovery, similar to findings in other studies40,41 involving sheep. Rapid transition from desflurane concentration to the brisk onset of swallowing and ability to lift the head suggested the rapid return of protective airway reflexes, which was evident in the present study. As a result, short intervals from discontinuation of desflurane anesthesia to extubation were observed. Rapid return of airway reflexes is advantageous in ruminant species that are at risk of regurgitation of ruminal contents, which may lead to aspiration pneumonia.25,27 Other factors that decrease the risk of regurgitation include withholding of food prior to anesthesia, proper placement of endotracheal tubes and insufflation of cuffs, and appropriate positioning of sheep.24
The pharmacokinetics of oxymorphone and hydromorphone in sheep has not been reported, to the authors’ knowledge, and these effects were not analyzed in the present study. Such data would have provided additional information about the clinical aspects of overall MAC reduction, drug distribution and metabolism, and administration frequency. A more remarkable MAC-sparing effect might have been identified for desflurane had other opioid doses been used. Published data regarding the distribution of opioid receptors within the CNS of sheep are lacking, and such information could lead to a better understanding of the effect of opioids in sheep. Brain-blood partition coefficients, which are required to calculate the time required for desflurane to equilibrate between blood and CNS, need to be determined for various species, including sheep.
The MACdes established in the sheep of the present study was similar to that established for other mammalian species. Information provided could be useful in the design of other studies to determine MACs of other inhalation anesthetics and MAC-sparing effects of other drugs in sheep. Oxymorphone and hydromorphone had a significant MAC-sparing effect on desflurane-anesthetized sheep at the doses used, confirming our initial hypothesis. However, this sparing effect was inferior to that reported for other species. Studies are needed to further investigate the effects of opioid administration on anesthetized sheep.
Acknowledgments
Supported in part by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (grant Nos. AA18166-27 and 5T35OD010991); the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University; and the Texas A&M Veterinary Medical Scientist Research Training Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
ABBREVIATIONS
| ETdes | End-tidal concentration of desflurane |
| MAC | Minimum alveolar concentration |
| MACdes | Minimum alveolar concentration of desflurane |
| MACdes+opioid | Minimum alveolar concentration of desflurane following opioid administration |
| Petco2 | End-tidal partial pressure of carbon dioxide |
| Spo2 | Oxygen saturation as measured by pulse oximetry |
Footnotes
Randomization plans. Available at: www.randomization.com. Accessed Mar 13, 2015.
Baxter, Deerfield, Ill.
VetOne, Boise, Idaho.
F-Circuit (10-foot), Smith Medical, Dublin, Ohio.
Datex-Ohmeda Tec 6 desflurane anesthesia vaporizer, GE Healthcare, Pittsburgh, Pa.
Hospira, Lake Forest, Ill.
Hallowell 2002, Hallowell EMC, Pittsfield, Mass.
Life Sciences, Irvine, Calif.
Swan-Ganz pulmonary arterial catheter, Life Sciences, Irvine, Calif.
PowerLab, AD Instruments, Colorado Springs, Colo.
BD Insyte, Becton Dickson Infusion Therapy, Sandy, Utah.
Transpac IV monitoring kit, ICU Medical, San Clemente, Calif.
Mind Ray, Shenzhen, Guangdong, China.
CareFusion, San Diego, Calif.
Endo Pharmaceuticals, Malvern, Pa.
West-Ward Pharmaceutical Corp, Chadds Ford, Pa.
Sigma Plot, version 10, SyStat Software, San Jose, Calif.
Schwarz U, Galankin JL, Biard JM, et al. The minimum alveolar concentration of desflurane in pregnant sheep (abstr). Anesthesiology 2003;99:A1443.
Lukasik VM, Nogami WM, Morgan SE. Minimum alveolar concentration and cardiovascular effects of desflurane in sheep (abstr). Vet Surg 1998;27:167.
Martinez EA, Lepiz M. Effect of remifentanil and fentanyl on minimum alveolar concentration and recovery in sevoflurane anesthetized dogs (abstr). Vet Anaesth Analg 2009;36:9.
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