A comparison of extradural and intravenous methadone on intraoperative isoflurane and postoperative analgesia requirements in dogs

Objective To compare the effects of intravenous (IV) and extradural (ED) methadone on end‐tidal isoflurane concentration (Fe ′ISO) and postoperative analgesic requirements in dogs undergoing femoro‐tibial joint surgery. Study Design Randomized, blinded, clinical study. Animals Twenty‐four healthy client‐owned dogs undergoing surgical repair of ruptured cruciate ligaments. Methods Dogs were randomly assigned to two groups of 12 animals and received either ED or IV methadone (0.3 mg kg^?1 diluted with saline to 0.2 mL kg^?1). Pre‐anaesthetic medication was IV acepromazine (0.05 mg kg^?1). Anaesthesia was induced with propofol and maintained initially with an Fe ′ISO of 1.0% delivered in oxygen. Methadone was injected with the dogs in sternal recumbency; the observer was unaware of the administration route. At 10 minutes (stimulation 1) and 20 minutes (stimulation 2) after methadone administration pelvic limb reflexes were tested by digit‐clamping. The time at skin incision (stimulation 3), joint‐capsule incision (stimulation 4), tibial tuberosity drilling (stimulation 5), fabellar suturing (stimulation 6) and extracapsular tightening (stimulation 7) were noted. Changes in heart rate (HR) and respiratory rate and arterial blood pressure associated with surgery were recorded along with the corresponding Fe ′ISO. After 20 minutes of anaesthesia, Fe ′ISO was decreased to the minimum required to maintain stable anaesthesia. Immediately after tracheal extubation, 1, 2, 3 and 6 hours postoperatively and on the morning after surgery, the degree of pain present was assessed using a numerical rating scale. The HR, respiratory rates and blood pressure were also recorded at these times. Serum cortisol and blood glucose concentrations were measured before pre‐anaesthetic medication and at each postoperative pain scoring interval except at 1 and 2 hours. Ketoprofen (2 mg kg^?1), carprofen (4 mg kg^?1) or meloxicam (0.2 mg kg^?1) were given by subcutaneous injection whenever pain scoring indicated moderate discomfort was present. Results Controlled ventilation was required in six dogs which stopped breathing after IV methadone. The median Fe ′ISO at stimulus 5 was 1.0% in the IV and 0.83% in the ED group. At stimulus 6, Fe ′ISO was 1.0% in the IV and 0.8% in the ED group; the difference was statistically significant (p ≤ 0.05). There was no significant difference in the duration of postoperative analgesia associated with administration route. Conclusions Extradural methadone significantly reduces the isoflurane requirement compared with IV methadone during femoro‐tibial joint surgery in dogs. Clinical relevance Extradural methadone provides safe and effective pain relief in dogs undergoing cruciate ligament repair.     

Isoflurane sparing action of epidurally administered xylazine hydrochloride in anesthetized dogs

OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.     

Effects of intravenously administered yohimbine on antinociceptive, cardiorespiratory, and postural changes induced by epidural administration of detomidine hydrochloride solution to healthy mares

OBJECTIVE: To determine effects of i.v. administered yohimbine on perineal analgesia, cardiovascular and respiratory activity, and head and pelvic limb position in healthy mares following epidural administration of detomidine hydrochloride solution. ANIMALS: 8 healthy mares. PROCEDURE: Each mare received detomidine hydrochloride (0.06 mg/kg of body weight), administered in the caudal epidural space, followed 61 minutes later by yohimbine (0.05 mg/kg; test) or sterile saline (0.9% NaCl) solution (control), administered i.v., in a randomized, crossover study design with > or = 2 weeks between treatments. Analgesia was determined by lack of sensory perception to electrical stimulation of perineal dermatomes and needle-prick stimulation of coccygeal to 15th thoracic dermatomes. Arterial pH, PaCO2, PaO2, heart and respiratory rates, rectal temperature, arterial blood pressure, and cardiac output were determined, and mares were observed for sweating and urination. Mean scores obtained for test and control groups were compared. RESULTS: Intravenously administered yohimbine significantly reduced mean scores of detomidine-induced perineal analgesia, head ptosis, changes in pelvic limb position, and sweating and diuresis; antagonized detomidine-induced decreases in heart rate and cardiac output; but did not affect detomidine-induced decrease in respiratory rate. CONCLUSIONS AND CLINICAL RELEVANCE: Most effects of epidurally administered detomidine, except bradypnea, were antagonized by yohimbine, suggesting that detomidine may influence respiratory rate by mechanisms other than stimulation of alpha2-adrenoceptors, or that yohimbine induces respiratory depressant effects. Yohimbine may be an effective alpha2-adrenoceptor antagonist for all but respiratory depression following epidural administration of detomidine to mares.     

Effect of morphine and flunixin meglumine on isoflurane minimum alveolar concentration in goats

OBJECTIVE: To determine the effect of morphine and flunixin meglumine on isoflurane (ISO) minimum alveolar concentration (MAC) in goats. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: Five adult, wether goats from 1 to 3 years in age, and weighing 24-65 kg. METHODS: Anesthesia was induced using ISO, which was delivered via a mask. Goats were intubated and ventilated to maintain an end-tidal carbon dioxide concentration between 25 and 30 mm Hg (3.3-4 kPa). End-tidal ISO concentration was measured using an infrared analyzer. The baseline ISO MAC that prevented purposeful movement in response to clamping a claw was determined. Following baseline MAC determination, each goat received one of the following four treatments intravenously (IV): morphine (2 mg kg(-1)), flunixin (1.5 mg kg(-1)), flunixin (1.5 mg kg(-1)) plus morphine (2 mg kg(-1)) or saline, and the MAC was re-determined. Goats were studied at weekly intervals, and each goat received each treatment in a randomized fashion. RESULTS: The baseline ISO MAC for the control treatment was 1.43%. Morphine reduced the MAC by 29.7%. Flunixin did not significantly decrease the MAC nor did it potentiate the effect of morphine on MAC. The quality of recovery was good in all cases. CONCLUSIONS: Morphine (2 mg kg(-1), IV) significantly reduced the ISO MAC in goats and did not adversely affect the quality of recovery. CLINICAL RELEVANCE: The use of morphine, at the dose studied, in association with ISO anesthesia, will allow a clinically significant reduction in the concentration of ISO required to maintain general anesthesia in goats.     

Effects of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflurane in dogs

Objective-To evaluate the effects of epidural administration of 3 doses of dexmedetomidine on isoflurane minimum alveolar concentration (MAC) and characterize changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determination in dogs. Animals-6 adult dogs. Procedures-Isoflurane-anesthetized dogs received physiologic saline (0.9% NaCl) solution (control treatment) or dexmedetomidine (1.5 [DEX1.5], 3.0 [DEX3], or 6.0 [DEX6] mug/kg) epidurally in a crossover study. Isoflurane MAC (determined by use of electrical nociceptive stimulation of the hind limb) was targeted to be accomplished at 2 and 4.5 hours. Changes in BIS attributable to nociceptive stimulation and cardiopulmonary data were recorded at each MAC determination. Results-With the control treatment, mean +/- SD MAC values did not change over time (1.57 +/- 0.23% and 1.55 +/- 0.25% at 2 and 4.5 hours, respectively). Compared with the control treatment, MAC was significantly lower at 2 hours (13% reduction) but not at 4.5 hours (7% reduction) in DEX1.5-treated dogs and significantly lower at 2 hours (29% reduction) and 4.5 hours (13% reduction) in DEX3-treated dogs. The DEX6 treatment yielded the greatest MAC reduction (31% and 22% at 2 and 4.5 hours, respectively). During all treatments, noxious stimulation increased BIS; but changes in BIS were correlated with increases in electromyographic activity. Conclusions and Clinical Relevance-In dogs, epidural administration of dexmedetomidine resulted in dose-dependent decreases in isoflurane MAC and that effect decreased over time. Changes in BIS during MAC determinations may not represent increased awareness because of the possible interference of electromyographic activity.     

Clinical evaluation of the anaesthetic sparing effect of brachial plexus block in cats

ObjectiveTo evaluate the isoflurane sparing effect and the post-surgical analgesia provided by a brachial plexus block (BPB) in cats undergoing distal thoracic limb surgery.Study designProspective randomized blinded clinical study.AnimalsTwenty client-owned cats.MethodsCats were assigned to receive either no BPB (group NB) or a nerve stimulator guided BPB (group BPB) using lidocaine (3.6 mg kg^?1) and bupivacaine (1.2 mg kg^?1). Pre-medication consisted of midazolam and ketamine intravenously (IV). Anaesthesia was induced with propofol IV to effect and maintained with isoflurane delivered in oxygen and a continuous rate infusion of fentanyl (2 μg kg^?1 hour^?1). End-tidal isoflurane concentration (Fe′ISO) was adjusted every 3 minutes guided by changes in cardiorespiratory parameters and reflexes present, to maintain a stable depth of anaesthesia. Five time points were chosen to record all parameters and compare values between groups. Recovery and post-operative pain assessment were performed using a visual analogue scale (VAS) at 15 and 45 minutes after extubation and thereafter at hourly intervals until 5 hours after placement of the BPB.ResultsNo clinically significant differences were seen for heart rate, respiratory rate and non-invasive blood pressure between groups. Mean Fe′ISO was significantly lower in group BPB compared with group NB at all time points. In group NB, all intraoperative measurements of Fe′ISO were significantly higher compared with baseline (3 minutes before start of surgery) measurements. During recovery, VAS scores for group BPB were significantly lower than for group NB. Additional analgesics were needed in all cats within the study period.Conclusion and Clinical relevanceIn cats undergoing orthopaedic surgery of the thoracic limb, BPB reduced intra-operative isoflurane requirement and pain during the early post-operative period when compared with procedures without a BPB. BPB is a useful adjunct to anaesthesia in such cases.     

Effects of methadone on the minimum alveolar concentration of isoflurane in dogs

ObjectiveTo investigate the effects of methadone on the minimum alveolar concentration of isoflurane (ISO_MAC) in dogs.Study designProspective, randomized cross-over experimental study.AnimalsSix adult mongrel dogs, four males and two females, weighing 22.8 ± 6.6 kg.MethodsAnimals were anesthetized with isoflurane and mechanically ventilated on three separate days, at least 1 week apart. Core temperature was maintained between 37.5 and 38.5 °C during ISO_MAC determinations. On each study day, ISO_MAC was determined using electrical stimulation of the antebrachium (50 V, 50 Hz, 10 mseconds) at 2.5 and 5 hours after intravenous injection of physiological saline (control) or one of two doses of methadone (0.5 or 1.0 mg kg^?1).ResultsMean (±SD) ISO_MAC in the control treatment was 1.19 ± 0.15% and 1.18 ± 0.15% at 2.5 and 5 hours, respectively. The 1.0 mg kg^?1 dose of methadone reduced ISO_MAC by 48% (2.5 hours) and by 30% (5 hours), whereas the 0.5 mg kg^?1 dose caused smaller reductions in ISO_MAC (35% and 15% reductions at 2.5 and 5 hours, respectively). Both doses of methadone decreased heart rate (HR), but the 1.0 mg kg^?1 dose was associated with greater negative chronotropic actions (HR 37% lower than control) and mild metabolic acidosis at 2.5 hours. Mean arterial pressure increased in the MET1.0 treatment (13% higher than control) at 2.5 hours.Conclusions and clinical relevanceMethadone reduces ISO_MAC in a dose-related fashion and this effect is lessened over time. Although the isoflurane sparing effect of the 0.5 mg kg^?1 dose of methadone was smaller in comparison to the 1.0 mg kg^?1 dose, the lower dose is recommended for clinical use because it results in less evidence of cardiovascular impairment.     

A comparison of the analgesic effects of caudal epidural methadone and lidocaine in the horse

Objective To evaluate and compare the effects of caudal epidural administration of methadone (METH) and lidocaine (LIDO) on tolerance to thermal stimulation over the dermatomes of the perineal, sacral, lumbar and thoracic regions in the horse. Study design A blinded, randomized, prospective, experimental cross‐over study. Animals Seven healthy horses, 15.7 ± 4.9 years (mean ± SD) of age, weighing 536 ± 37 kg. Methods The horses were randomly assigned to receive two treatments (group M: METH, 0.1 mg kg^?1 or group L: LIDO, 0.35 mg kg^?1) at intervals of at least 28 days. An 18‐gauge 80‐mm Tuohy epidural needle was placed in the first intercoccygeal space (Co1–Co2) in awake standing horses restrained in stocks. Analgesia was assessed by use of a probe maintained at a constant 62 °C by circulating hot water. The maximum stimulation time was 30 seconds. Bilateral stimulation was performed at five defined points. Before drug administration, baseline values of response time to thermal stimuli were obtained. Time to response was then measured 15 and 60 minutes after METH or LIDO administration and then hourly until the response returned to baseline at all stimulation points on two further assessments. Development of any ataxia and/or sedation was recorded. Positive pain responses were defined as purposeful avoidance movements of the head, neck, trunk, limbs and tail. Absence of attempts to kick, bite and turning of the head toward the stimulation site were used to indicate analgesia. Results Caudal epidural administration of METH and LIDO significantly increased reaction time to thermal stimulation (one‐sample t‐test; p = 0.05). Analgesia in the perineal region was present 15 minutes after both METH and LIDO administration and progressed from caudal to cranial dermatones with time. The duration of a significant increase in reaction time was 5 hours after METH injection compared to 3 hours following LIDO. All horses defaecated and urinated normally, and no excitement, sedation or ataxia were observed after METH administration. The horses were unable to defaecate normally and were moderately to severely ataxic with hindlimb weakness after LIDO. Conclusions Caudal epidural administration of methadone has considerable potential in the management of perineal, lumbo‐sacral and thoracic pain in horses. Regional differences exist in the onset, duration and intensity of the pain relief. Clinical relevance Epidural methadone administration provides analgesia with no measured side effects in these healthy adult horses.     

Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE: To determine the effect of IV administration of perzinfotel on the minimum alveolar concentration (MAC) of isoflurane in dogs. Animals-6 healthy sexually intact male Beagles. PROCEDURES: Dogs were instrumented with a telemetry device that permitted continuous monitoring of heart rate, arterial blood pressure, and body temperature. Dogs were anesthetized with propofol (4 to 6 mg/kg, IV) and isoflurane for 30 minutes before determination of MAC of isoflurane. Isoflurane MAC values were determined 4 times, separated by a minimum of 7 days, before and after IV administration of perzinfotel (0 [control], 5, 10, and 20 mg/kg). Bispectral index and percentage hemoglobin saturation with oxygen (SpO(2)) were monitored throughout anesthesia. RESULTS: Isoflurane MAC was 1.32 +/- 0.14%. Intravenous administration of perzinfotel at 0, 5, 10, and 20 mg/kg decreased isoflurane MAC by 0%, 24%, 30%, and 47%, respectively. Perzinfotel significantly decreased isoflurane MAC values, compared with baseline and control values. The bispectral index typically increased with higher doses of perzinfotel and lower isoflurane concentrations, but not significantly. Heart rate, body temperature, and SpO(2) did not change, but systolic, mean, and diastolic arterial blood pressures significantly increased with decreases in isoflurane MAC after administration of perzinfotel at 10 and 20 mg/kg, compared with 0 and 5 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of perzinfotel decreased isoflurane MAC values. Improved hemodynamics were associated with decreases in isoflurane concentration.     

Determination of the sevoflurane sparing effect of methadone in cats

ObjectiveTo determine the magnitude and duration of sevoflurane minimum alveolar concentration (MAC) reduction following a single intravenous (IV) dose of methadone in cats.Study designProspective experimental study.AnimalsEight (four females and four males) healthy mixed-breed adult (1–2 years) cats weighing 5.82 ± 0.42 kg.MethodsAnesthesia was induced and maintained with sevoflurane. Intravenous catheters facilitated administration of methadone and lactated Ringer’s solution. After baseline MAC determination in triplicate using a tail clamp technique, 0.3 mg kg^?1 of methadone was administered IV. End-tidal sevoflurane concentration (e′SEVO) was reduced and MAC was redetermined. In an effort to determine the duration of MAC reduction, measurements were repeated in a stepwise manner until MAC values returned to baseline. After the last stimulation, the e′SEVO was increased to 1.2 individual MAC for 15 minutes, then sevoflurane was discontinued and cats were allowed to recover from anesthesia.ResultsBaseline sevoflurane MAC was 3.18 ± 0.06%. When compared with baseline the sevoflurane MAC after methadone administration was significantly reduced by 25, 15 and 7% at 26, 76 and 122 minutes, respectively. The final MAC value (3.09 ± 0.07%) determined 156 minutes after methadone administration was not significantly different from baseline.Conclusions and clinical relevanceIntravenous methadone (0.3 mg kg^?1) significantly decreased MAC of sevoflurane in cats but the effect was short-lived.     

Comparisons of the effects of acupuncture, electroacupuncture, and transcutaneous cranial electrical stimulation on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE: To compare the effects of acupuncture (AP), electroacupuncture (EA), and transcutaneous cranial electrical stimulation (TCES) with high-frequency intermittent currents on the minimum alveolar concentration (MAC) of isoflurane and associated cardiovascular variables in dogs. ANIMALS: 8 healthy adult female Beagles. PROCEDURE: Each dog was anesthetized with isoflurane on 4 occasions, allowing a minimum of 10 days between experiments. Isoflurane MAC values were determined for each dog without treatment (controls) and after treatment with AP and EA (AP points included the Large Intestine 4, Lung 7, Governing Vessel 20, Governing Vessel 14, San Tai, and Baihui) and TCES. Isoflurane MAC values were determined by use of noxious electrical buccal stimulation. Heart rate, mean arterial blood pressure (MAP), arterial blood oxygen saturation (Spo2) measured by use of pulse oximetry, esophageal body temperature, inspired and expired end-tidal isoflurane concentrations, end-tidal carbon dioxide concentration, and bispectral index (BIS) were monitored. Blood samples were collected for determination of plasma cortisol concentration. RESULTS: Mean +/- SD baseline MAC of isoflurane was 1.19 +/- 0.1%. Acupuncture did not significantly change MAC of isoflurane. Treatments with EA and TCES significantly lowered the MAC of isoflurane by 10.1% and 13.4%, respectively. The Spo2, heart rate, MAP, BIS, esophageal body temperature, and plasma cortisol concentration were not significantly different after AP, EA, TCES, and control treatments at any time interval. CONCLUSIONS AND CLINICAL RELEVANCE: Use of EA and TCES decreased MAC of isoflurane in dogs without inducing adverse hemodynamic effects. However, the reduction in isoflurane MAC by EA andTCES treatments was not considered clinically relevant.     

Effect of oral trazodone on the minimum alveolar concentration of isoflurane in dogs

Objective

To determine the effect of oral trazodone on the minimum alveolar concentration (MAC) of isoflurane in dogs.

The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs

Objectives To determine whether moderate hypothermia during anesthesia significantly affects the serum concentration of transdermally delivered fentanyl and whether halothane or isoflurane affect these concentrations. Study Design Randomized cross‐over experimental trial. Animals Six mature, healthy Beagles (three males, three females) weighing 10.6 ± 0.43 kg. Methods A 50‐µg hour^?1 fentanyl patch was applied 36 hours prior to anesthesia. Anesthesia was induced at time 0 (t = 0). Each dog received four treatments: isoflurane + normothermia (ISO‐NORM), isoflurane + hypothermia (ISO‐HYPO), halothane + normothermia (HAL‐NORM), and halothane + hypothermia (HAL‐HYPO). Dogs were intubated and maintained at 1.5 times MAC. Animals in the hypothermia treatments were cooled to 35 °C during anesthesia. Serum fentanyl analysis was performed at ?36, ?24, ?12, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 18, and 26 hours. Direct arterial blood pressures and arterial blood gases were monitored. Results The mean body temperatures (±SEM) during the anesthetic period for the four treatments were: ISO‐NORM = 37.7 ± 0.07 °C, ISO‐HYPO = 35.8 ± 0.1 °C, HAL‐NORM = 37.7 ± 0.06 °C, and HAL‐HYPO = 35.8 ± 0.13 °C. The mean (±SEM) serum fentanyl concentrations (SFC) for both hypothermia treatments were significantly lower than baseline concentrations at t = 1 hour and persisted for the duration of anesthesia for the ISO‐HYPO treatment but only from t = 1 to 2 hours for the HAL‐HYPO treatment. Serum fentanyl concentrations returned to baseline within one hour of the end of anesthesia, regardless of body temperature. There were no significant differences between treatments for systolic or diastolic blood pressure but mean blood pressures were higher during normothermia versus hypothermia during the last hour of anesthesia. Conclusions and clinical relevance Hypothermia during inhalation anesthesia produced a significant reduction in SFC using transdermal administration and was more protracted with isoflurane than halothane anesthesia. While significant reductions in SFC occurred, the SFC were still within the range believed to confer analgesia.     

Prior determination of baseline minimum alveolar concentration (MAC) of isoflurane does not influence the effect of ketamine on MAC in rabbits

The objective of this study was to compare the effect on the minimum alveolar concentration (MAC) of isoflurane when ketamine was administered either after or without prior determination of the baseline MAC of isoflurane in rabbits. Using a prospective randomized crossover study, 8 adult, female New Zealand rabbits were allocated to 2 treatment groups. Anesthesia was induced and maintained with isoflurane. Group 1 (same-day determination) had the MAC-sparing effect of ketamine [1 mg/kg bodyweight (BW) bolus followed by a constant rate infusion (CRI) of 40 μg/kg BW per min, given by intravenous (IV)], which was determined after the baseline MAC of isoflurane was determined beforehand. A third MAC determination was started 30 min after stopping the CRI. Group 2 (separate-day determination) had the MAC-sparing effect of ketamine determined without previous determination of the baseline MAC of isoflurane. A second MAC determination was started 30 min after stopping the CRI. In group 1, the MAC of isoflurane (2.15 ± 0.09%) was significantly decreased by ketamine (1.63 ± 0.07%). After stopping the CRI, the MAC was significantly less (2.04 ± 0.11%) than the baseline MAC of isoflurane and significantly greater than the MAC during the CRI. In group 2, ketamine decreased isoflurane MAC (1.53 ± 0.22%) and the MAC increased significantly (1.94 ± 0.25%) after stopping the CRI. Minimum alveolar concentration (MAC) values did not differ significantly between the groups either during ketamine administration or after stopping ketamine. Under the study conditions, prior determination of the baseline isoflurane MAC did not alter the effect of ketamine on MAC. Both methods of determining MAC seemed to be valid for research purposes.     

The effect of epidural morphine on the minimum alveolar concentration of isoflurane in cats

This study was undertaken to evaluate the effect of 3 different doses of epidurally administered morphine sulphate on the minimum alveolar concentration (MAC) of isoflurane in healthy cats. Five 4-year-old, spayed female cats weighing 4.7 ± 0.8 kg were allocated randomly to receive one of 3 doses of morphine on each study day. The 3 doses of morphine were 0.05, 0.1 and 0.2 mg/kg bwt and each cat was studied 3 times so that each cat received all doses. On each study day, cats were anaesthetised with isoflurane and instrumented. The MAC of isoflurane was determined in triplicate and morphine sulphate was administered via an epidural catheter chronically implanted prior to the study. Maximum MAC reduction was determined over the following 2 h. At the end of the study cats were allowed to recover. There was a significant reduction in MAC of isoflurane, with all doses of epidural morphine (P<0.05). The maximum reduction in MAC of isoflurane after 0.05 mg/kg bwt, 0.10 mg/kg bwt and 0.20 mg/kg bwt morphine was 21.4 ± 9.796, 30.8 ± 9.696, and 30.2 ± 6.8%, respectively, with no significant difference between doses. Systolic, mean and diastolic blood pressure, heart rate, respiratory rate and arterial pH decreased significantly whereas arterial carbon dioxide tension increased significantly after morphine administration (P<0.05). The means for all variables returned to pre-morphine values when the end-tidal isoflurane concentration was reduced to the new MAC point. In conclusion, epidural morphine decreased the concentration of isoflurane required to prevent movement in response to noxious mechanical stimulation to the tail base. A similar effect may be seen clinically allowing lower doses of isoflurane to be used to provide surgical anaesthesia for procedures involving the hind limbs, pelvis and tail.     

Interactions of morphine and isoflurane in horses

OBJECTIVE: To quantitate dose- and time-related magnitudes of interactive effects of morphine (MOR) and isoflurane (ISO) in horses and to characterize pharmacokinetics of MOR in plasma and the ventilatory response to MOR during administration of ISO. ANIMALS: 6 adult horses. PROCEDURE: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of ISO in O2 and then to characterize the change in anesthetic requirement as defined by the alteration in ISO MAC following IV administration of saline (0.9% NaCl) solution and 2 doses of MOR (low dose, 0.25 mg/kg; high dose, 2.0 mg/kg). Arterial blood samples were obtained before and after MOR and analyzed. RESULTS: Mean +/- SD baseline ISO MAC was 1.43 +/- 0.06%. The ISO MAC did not change with time after administration of saline solution. Effects of MOR on ISO MAC varied. Maximal change in MAC ranged from -20.2 to +28.3% and -18.9 to +56.2% after low and high doses of MOR, respectively. Typical half-life of MOR in plasma was 40 to 60 minutes and related to dose. Mean PaCO2 increased from 70 mm Hg before MOR to 88 to 102 mm Hg for 30 to 240 minutes after the high dose of MOR. Recovery from anesthesia after administration of the high dose of MOR was considered undesirable and dangerous. CONCLUSIONS AND CLINICAL RELEVANCE: Our results do not support routine clinical use of MOR administered IV at dosages of 0.25 or 2.0 mg/kg as an adjuvant to anesthesia in horses administered ISO.     

Naltrexone does not affect isoflurane minimum alveolar concentration in cats

ObjectiveTo test whether naltrexone, an opioid receptor antagonist, affects the minimum alveolar concentration (MAC) of isoflurane in cats, a species that is relatively resistant to the general anesthetic sparing effects of most opioids.Study designRandomized, crossover, placebo-controlled, blinded experimental design.AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg.MethodsThe cats were studied twice. In the first study, baseline isoflurane MAC was measured in duplicate. The drug (saline control or 0.6 mg kg^?1 naltrexone) was administered IV every 40–60 minutes, and isoflurane MAC was re-measured. In the second study, cats received the second drug treatment using identical methods 2 weeks later.ResultsIsoflurane MAC was 2.03 ± 0.12% and was unchanged from baseline following saline or naltrexone administration.Conclusion and clinical relevanceMinimum alveolar concentration was unaffected by naltrexone. Because MAC in cats is unaffected by at least some mu-opioid agonists and antagonists, spinal neurons that are directly modulated by mu-opioid receptors in this species cannot be the neuroanatomic sites responsible for immobility from inhaled anesthetics.     

Effects of fentanyl on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

The effects of fentanyl on the minimum alveolar concentration (MAC) of isoflurane and cardiovascular function in mechanically ventilated goats were evaluated using six healthy goats (three does and three wethers). Following induction of general anaesthesia with isoflurane delivered via a mask, endotracheal intubation was performed and anaesthesia was maintained with isoflurane. The baseline MAC of isoflurane (that is, the lowest alveolar concentration required to prevent gross purposeful movement) in response to clamping a claw with a vulsellum forceps was determined. Immediately after baseline isoflurane MAC determination, the goats received, on separate occasions, one of three fentanyl treatments, administered intravenously: a bolus of 0.005 mg/kg followed by constant rate infusion (CRI) of 0.005 mg/kg/hour (treatment LFENT), a bolus of 0.015 mg/kg followed by CRI of 0.015 mg/kg/hour (treatment MFENT) or a bolus of 0.03 mg/kg followed by CRI of 0.03 mg/kg/hour (treatment HFENT). Isoflurane MAC was redetermined during the fentanyl CRI treatments. Cardiopulmonary parameters were monitored. A four-week washout period was allowed between treatments. The observed baseline isoflurane MAC was 1.32 (1.29 to 1.36) per cent. Isoflurane MAC decreased to 0.98 (0.92 to 1.01) per cent, 0.75 (0.69 to 0.79) per cent and 0.58 (0.51 to 0.65) per cent following LFENT, MFENT and HFENT respectively. Cardiovascular function was not adversely affected. The quality of recovery from general anaesthesia was good, although exaggerated tail-wagging was observed in some goats following MFENT and HFENT.     

Analgesic, hemodynamic, and respiratory effects induced by caudal epidural administration of meperidine hydrochloride in mares.

OBJECTIVE: To determine the analgesic, hemodynamic, and respiratory effects induced by caudal epidural administration of meperidine hydrochloride in mares. ANIMALS: 7 healthy mares. Procedure: Each mare received meperidine (5%; 0.8 mg/kg of body weight) or saline (0.9% NaCl) solution via caudal epidural injection on 2 occasions. At least 2 weeks elapsed between treatments. Degree of analgesia in response to noxious electrical, thermal, and skin and muscle prick stimuli was determined before and for 5 hours after treatment. In addition, cardiovascular and respiratory variables were measured and degree of sedation (head position) and ataxia (pelvic limb position) evaluated. RESULTS: Caudal epidural administration of meperidine induced bilateral analgesia extending from the. coccygeal to S1 dermatomes in standing mares; degree of sedation and ataxia was minimal. Mean (+/- SD) onset of analgesia was 12 +/- 4 minutes after meperidine administration, and duration of analgesia ranged from 240 minutes to the entire 300-minute testing period. Heart and respiratory rates, rectal temperature, arterial blood pressures, Hct, PaO2, PaCO2, pHa, total solids and bicarbonate concentrations, and base excess were not significantly different from baseline values after caudal epidural administration of either meperidine or saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Caudal epidural administration of meperidine induced prolonged perineal analgesia in healthy mares. Degree of sedation and ataxia was minimal, and adverse cardiorespiratory effects were not detected. Meperidine may be a useful agent for induction of caudal epidural analgesia in mares undergoing prolonged diagnostic, obstetric, or surgical procedures in the anal and perineal regions.     

The effect of epidural injection speed on epidural pressure and distribution of solution in anesthetized dogs

ObjectiveTo determine the effect of injection speed on epidural pressure (EP), injection pressure (IP), epidural distribution (ED) of solution, and extent of sensory blockade (SB) during lumbosacral epidural anesthesia in dogs.Study designProspective experimental trial.AnimalsTen healthy adult Beagle dogs weighing 8.7 ± 1.6 kg.MethodsGeneral anesthesia was induced with propofol administered intravenously and maintained with isoflurane. Keeping the dogs in sternal recumbency, two spinal needles connected to electrical pressure transducers were inserted into the L6-L7 and the L7-S1 intervertebral epidural spaces for EP and IP measurements, respectively. Bupivacaine 0.5% diluted in iohexol was administered epidurally to each dog via spinal needle at L7-S1 intervertebral space, at two rates of injection (1 and 2 mL minute^?1 groups), with a 1-week washout period. Epidural distribution was verified with computed tomography, and SB was evaluated after arousal by pinching the skin with a mosquito hemostatic forceps over the vertebral dermatomes. The results were analyzed according to each injection speed, using paired t- and Wilcoxon signed-rank tests.ResultsMean ± SD of baseline EP and IP values were 2.1 ± 6.1 and 2.6 ± 7.1 mmHg, respectively. Significant differences were observed between 1 and 2 mL minute^?1 groups for peak EP (23.1 ± 8.5 and 35.0 ± 14.5 mmHg, p = 0.047) and peak IP (68.5 ± 10.7 and 144.7 ± 32.6 mmHg, p <0.001). However, the median (range) of the ED, 11.5 (4–22) and 12 (5–21) vertebrae, and SB, 3.5 (0–20) and 1 (0–20) dermatomes, values of the two groups were not related to injection speed.Conclusions and clinical relevanceThe EP profile during injection was measured by separating the injection and pressure monitoring lines. The increase in epidural injection speed increased the EP, but not the ED or the SB in dogs.