Clinical effects of a constant rate infusion of remifentanil, alone or in combination with ketamine, in cats anesthetized with isoflurane

Paulo V. M. Steagall Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC J2S 2M2, Canada.

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Monica Aucoin Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC J2S 2M2, Canada.

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Beatriz P. Monteiro Department of Biomedical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC J2S 2M2, Canada.

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Maxim Moreau Department of Biomedical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC J2S 2M2, Canada.

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Brad T. Simon Department of Clinical Sciences, School of Veterinary Medicine, Ross University, St Kitts, West Indies.

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Patrick M. Burns Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC J2S 2M2, Canada.

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Abstract

Objective—To evaluate the effects of a constant rate infusion of remifentanil, alone or in combination with ketamine, in healthy cats anesthetized with isoflurane.

Design—Randomized, controlled, clinical trial.

Animals—23 cats undergoing elective ovariohysterectomy.

Procedures—Cats were premedicated with acepromazine and morphine; anesthesia was induced with propofol and maintained with isoflurane. Cats were given constant rate infusions of remifentanil (20 μg/kg/h [9 μg/lb/h], IV; n = 8), remifentanil and ketamine (0.5 mg/kg [0.23 mg/lb], then 1.8 mg/kg/h [0.82 mg/lb/h], IV; 7), or crystalloid fluids (8). The anesthesiologist was blinded to treatment group, end-tidal isoflurane concentration, and vaporizer setting. Heart rate, systolic arterial blood pressure, respiratory rate, end-tidal partial pressure of CO2, temperature, and end-tidal isoflurane concentration were monitored; recovery scores were assigned.

Results—There were no significant differences among treatment groups with respect to age, body weight, surgery time, anesthesia time, time to extubation, recovery score, or cardiorespiratory variables. End-tidal isoflurane concentration was significantly reduced in cats given remifentanil and ketamine (mean ± SD, 0.63 ± 0.4%), compared with concentration in cats given crystalloid fluids (1.22 ± 0.5%) but not compared with concentration in cats given remifentanil alone (1.03 ± 0.4%). Compared with cats given crystalloid fluids, mean isoflurane requirement was reduced by 48.3% in cats given remifentanil-ketamine and 15.6% in cats given remifentanil alone.

Conclusions and Clinical Relevance—At the dosages administered, a constant rate infusion of remifentanil-ketamine resulted in a significant decrease in the isoflurane requirement in healthy cats undergoing ovariohysterectomy. However, significant differences in cardiovascular variables were not observed among treatment groups.

Abstract

Objective—To evaluate the effects of a constant rate infusion of remifentanil, alone or in combination with ketamine, in healthy cats anesthetized with isoflurane.

Design—Randomized, controlled, clinical trial.

Animals—23 cats undergoing elective ovariohysterectomy.

Procedures—Cats were premedicated with acepromazine and morphine; anesthesia was induced with propofol and maintained with isoflurane. Cats were given constant rate infusions of remifentanil (20 μg/kg/h [9 μg/lb/h], IV; n = 8), remifentanil and ketamine (0.5 mg/kg [0.23 mg/lb], then 1.8 mg/kg/h [0.82 mg/lb/h], IV; 7), or crystalloid fluids (8). The anesthesiologist was blinded to treatment group, end-tidal isoflurane concentration, and vaporizer setting. Heart rate, systolic arterial blood pressure, respiratory rate, end-tidal partial pressure of CO2, temperature, and end-tidal isoflurane concentration were monitored; recovery scores were assigned.

Results—There were no significant differences among treatment groups with respect to age, body weight, surgery time, anesthesia time, time to extubation, recovery score, or cardiorespiratory variables. End-tidal isoflurane concentration was significantly reduced in cats given remifentanil and ketamine (mean ± SD, 0.63 ± 0.4%), compared with concentration in cats given crystalloid fluids (1.22 ± 0.5%) but not compared with concentration in cats given remifentanil alone (1.03 ± 0.4%). Compared with cats given crystalloid fluids, mean isoflurane requirement was reduced by 48.3% in cats given remifentanil-ketamine and 15.6% in cats given remifentanil alone.

Conclusions and Clinical Relevance—At the dosages administered, a constant rate infusion of remifentanil-ketamine resulted in a significant decrease in the isoflurane requirement in healthy cats undergoing ovariohysterectomy. However, significant differences in cardiovascular variables were not observed among treatment groups.

Balanced anesthesia involves administration of a combination of drugs that provides analgesia, anesthesia, and muscular relaxation. This technique may minimize analgesic requirements and decrease anesthetic-induced adverse effects.1 Studies1,2 have demonstrated the benefits of this technique in dogs and cats.

Opioids are the cornerstone of pain management in small animal practice and are widely used as part of a balanced anesthetic technique. Remifentanil is a short-acting synthetic μ-opioid receptor agonist that has a rapid onset and short duration of action with rapid clearance, which makes it suitable for infusion regimens in cats.3 The drug has been shown to reduce the MAC of isoflurane by approximately 25% in cats; however, this MAC-sparing effect has not been demonstrated in all studies.4,5 In cats, reductions in the MAC of inhalation anesthetics after opioid administration are lower in magnitude than those reported for dogs.4,6 In addition, our experience has been that in cats, infusion of an opioid alone may not always provide consistent and adequate pain management in the perioperative period. This can be particularly true for cats with systemic disease or multiple trauma that have severe pain. In these instances, other analgesic techniques are used to optimize pain relief.7

Ketamine is a dissociative anesthetic and noncompetitive antagonist of the N-methyl-d-aspartate receptor that has been shown to decrease the MAC of isoflurane in cats.8 In addition to its inhalation anesthetic–sparing effects, the drug can be infused as an adjunctive analgesic agent to minimize central sensitization while potentially decreasing opioid requirements.7 Ketamine may also be combined with an opioid infusion to optimize inhalation anesthetic–sparing effects and improve the quality of anesthesia. To the authors’ knowledge, however, the inhalation anesthetic–sparing effects and effects on cardiovascular function of an opioid-ketamine infusion have not been studied in cats.

The purpose of the study reported here was to evaluate the effects of a CRI of remifentanil, alone or in combination with ketamine, on isoflurane requirements, cardiovascular function, and anesthetic recovery in healthy cats undergoing elective ovariohysterectomy. Our hypothesis was that the combination of remifentanil and ketamine would induce significantly greater isoflurane-sparing effects than either remifentanil alone or crystalloid fluids alone.

Materials and Methods

The study protocol was approved by the animal care committee of the University of Montreal Faculty of Veterinary Medicine (13-Rech-1720).

Animals—The study was designed as a randomized, controlled, clinical trial. Twenty-four client-owned mixed-breed healthy adult female cats scheduled for elective ovariohysterectomy were enrolled in the study. Owners of all cats included in the study provided written informed consent. Cats were considered healthy on the basis of medical history and results of a physical examination and hematologic testing. Exclusion criteria included aggression, cardiac arrhythmias, pregnancy, obesity (body condition score > 7 on a scale from 1 to 9), anemia, and clinical signs of disease. On the day before surgery, abdominal ultrasonography was performed to ensure that cats were not pregnant. Cats were randomly assigned by means of an online software programa to a remifentanil-ketamine group, remifentanil group, or control group (n = 8/group).

Anesthetic protocol and monitoring—Food but not water was withheld for up to 10 hours before anesthesia. Cats were premedicated with acepromazine (0.03 mg/kg [0.014 mg/lb], IM) and morphine (0.3 mg/kg [0.14 mg/lb], IM) injected into the epaxial muscles. Approximately 20 minutes later, a 22-gauge IV catheter was introduced into a cephalic vein under aseptic conditions, and propofol was administered IV slowly to effect. Lidocaine (2 mg) was instilled on the vocal cords, and cats were intubated with an appropriately sized, cuffed endotracheal tube. Anesthesia was maintained with isofluraneb administered with oxygen through a calibrated, precision, out-of circuit vaporizerc and nonrebreathing systemd with an oxygen flow rate of 250 mL/kg/min (114 mL/lb/min). A tom-cat catheter was introduced through the lumen of the endotracheal tube to continuously measure inspired isoflurane concentration, ETiso and Petco2 with a gas analyzere calibrated before each experiment with a standard gas mixture provided by the manufacturer. Respiratory rate was derived from the capnogram. Cats were positioned in dorsal recumbency over a circulating warm-water blanket.f Intermittent positive-pressure ventilation was provided with a standard ventilatorg adjusted to maintain normocapnia (30 to 45 mm Hg). Body temperature was monitored with an esophageal temperature probe. Systolic blood pressure was measured with a Doppler ultrasonic flow detector.h The cuff was placed around the antebrachium; a cuff with a width approximately 40% of the circumference of the limb was used. Heart rate and rhythm were monitored by means of a continuous lead II ECG tracing; Spo2 was monitored with a pulse oximeter with the sensor attached to the cat's tongue.

Experimental procedure—Five minutes after anesthesia was induced, a CRI of remifentanil and ketamine, remifentanil alone, or crystalloid fluids alone (control group) was begun. For the remifentanil-ketamine group, remifentanili was administered as a CRI (20 μg/kg/h [9.09 μg/lb/h], IV) in saline (0.9% NaCl) solution and ketaminej was administered as a bolus (0.5 mg/kg [0.23 mg/lb], IV) followed by a CRI (1.8 mg/kg/h [0.82 mg/lb/h], IV). For the ketamine CRI, ketamine was added to lactated Ringer's solution, which was administered at a rate of 10 mL/kg/h (4.5 mL/lb/h), IV, throughout surgery by use of a fluid infusion device.k

For the remifentanil group, remifentanil was administered as a CRI (20 μg/kg/h, IV) in saline solution. In addition, a bolus of saline solution equivalent to the volume of the ketamine bolus given to cats in the remifentanil-ketamine group was administered, and lactated Ringer's solution was administered at a rate of 10 mL/kg/h, IV, throughout surgery.

For the control group, a CRI of saline solution equivalent to the remifentanil CRI given to cats in the remifentanil-ketamine and remifentanil groups was administered. In addition, a bolus of saline solution equivalent to the volume of the ketamine bolus given to cats in the remifentanil-ketamine group was administered, and lactated Ringer's solution was administered at a rate of 10 mL/kg/h, IV, throughout surgery.

The ketamine or saline solution bolus was administered over 5 seconds, and the CRIs were started immediately afterward. A syringe infusion driverl was used to administer the remifentanil or saline solution CRI. Surgery was begun approximately 5 to 7 minutes after the CRIs were begun. All treatments were calculated and administered by a single individual (PMB) who was not involved with the assessment or control of anesthetic depth.

For all cats, a single board-certified anesthesiologist (PVMS) adjusted the depth of anesthesia on the basis of jaw tone, palpebral reflexes, eye position, and response to instrumentation and surgery. This individual was blinded to treatment group, inspired and end-tidal isoflurane concentrations, and vaporizer setting. To blind the anesthesiologist to vaporizer setting, a piece of white tape was used to completely cover the dial. Tachycardia (heart rate > 160 beats/min) and hypertension (SBP > 160 mm Hg) were considered acceptable during rupture of the suspensory ligament if depth of anesthesia was considered to be adequate otherwise and no other responses to surgical stimulation were observed.

All surgeries were performed by a single, experienced surgeon (BPM). Briefly, a 3- to 4-cm-long ventral midline incision was made through the skin, subcutaneous tissues, and aponeurosis of the rectus abdominis muscle, and a modified 3-clamp technique was used. The abdominal wall and subcutaneous tissues were closed with a simple continuous pattern of absorbable suture material. The skin was closed with an intradermal suture pattern.

Data were recorded at baseline immediately before the beginning of the skin incision (T0), at the end of the celiotomy (T1), during traction and ligation of the left ovarian pedicle (T2), during traction and ligation of the right ovarian pedicle (T3), during hysterectomy (T4), at the mid-point of the abdominal closure (T5), at the mid-point of the subcutaneous closure (T6), and at the mid-point of the intradermal closure (T7).

All infusions were stopped at T5. Surgery time (time elapsed from the first incision until placement of the last suture), anesthesia time (time elapsed from injection of propofol to turning off the vaporizer dial), and time to extubation (time elapsed from turning off the vaporizer dial until extubation) were recorded for each cat. Extubation was performed once the cats’ palpebral reflexes were evident, as is commonly performed at our institution. Postoperative analgesia was provided by administering meloxicam (0.2 mg/kg [0.09 mg/lb], SC) and buprenorphine (0.02 mg/kg [0.009 mg/lb], IV) after extubation. Cats were examined for signs of pain for up to 8 hours after surgery, and a second dose of buprenorphine (0.02 mg/kg, IM) was given if needed. Cats received a second dose of meloxicam (0.05 mg/kg [0.023 mg/lb], PO) 24 hours after extubation.

Quality of anesthetic recovery was scored by observing the cat for 15 minutes after extubation. Scoring was done by the anesthesiologist (PMVS), who used a simple descriptive scale from 1 to 4, where 1 = excellent recovery, calm and comfortable, stretching, possible kneading with forepaws, ideal; 2 = good recovery, comfortable but with mild agitation; 3 = acceptable recovery, moderate agitation but acceptable, no thrashing or dysphoria; and 4 = poor recovery, thrashing, severe agitation, dysphoria, unacceptable.

Statistical analysis—Data were tested for normality with a Shapiro-Wilk test and were log-transformed when appropriate. Repeated-measures general linear mixed models were used to test for differences in respiratory rate, heart rate, SBP, Spo2, Petco2, ETiso, and esophageal temperature between groups and over time. Models included 2 fixed effects (time and treatment) and their interaction; cat was included as a random effect. The Akaike information criterion was used to determine the best covariance structure. When appropriate, body weight was used as a covariable to improve the model. General linear mixed models were used to compare age, body weight, surgery time, anesthesia time, time to extubation, and propofol dose among treatment groups. Similarly, a general linear model was used to compare recovery scores among groups. Post hoc analyses were performed when appropriate with the Bonferroni procedure. Data were summarized as mean ± SD or as median and range. All statistical analyses were performed with standard software.m Values of P < 0.05 were considered significant.

Results

One cat in the remifentanil-ketamine group developed complications; therefore, data from this cat were excluded from analyses. All cats were discharged from the hospital at least 24 hours after surgery; none of the cats developed any postoperative complications. Age, body weight, surgery time, anesthesia time, and time to extubation were not significantly different among treatment groups. The dose of propofol used for induction of anesthesia was significantly (P = 0.029) higher for cats in the remifentanil-ketamine group than for cats in the control group (Table 1). Respiratory rate and Spo2 did not differ significantly over time or among treatment groups. Significant time effects were observed for heart rate (P = 0.001), SBP (P = 0.001), Petco2 (P = 0.031), and esophageal temperature (P = 0.001; Table 2). However, heart rate, SBP, Petco2, and esophageal temperature were not significantly different among treatment groups.

Table 1—

Comparison of age, body weight, propofol dose, surgery time, anesthesia time, time to extubation, and recovery score for healthy cats undergoing elective ovariohysterectomy that were anesthetized with isoflurane and given CRIs of remifentanil and ketamine (n = 7), remifentanil alone (8), or crystalloid fluids alone (control group; 8).

Treatment groupAge (mo)Body weight (kg)Propofol dose (mg/kg)Surgery time (min)Anesthesia time (min)Time to extubation (min)Recovery quality*
Remifentanilketamine15 (7–36)3.2 (2.9–6.1)7.9 ± 1.9†31.6 ± 6.844.6 ± 8.11.9 ± 0.92 (1–3)
Remifentanil18 (5–96)3.0 (2.5–4.8)6.8 ± 1.234.3 ± 7.846.6 ± 6.73.8 ± 2.12 (1–2)
Control12 (7–48)3.4 (2.8–4.3)5.9 ± 0.737.0 ± 8.351.5 ± 9.22.8 ± 2.02 (1–3)

Data are reported as mean ± SD or median (range). To convert mg/kg to mg/lb, divide by 2.2.

Recovery quality was scored on a scale from 1 (ideal) to 4 (unacceptable). †Significantly (P = 0.029) different from value for cats in the control group.

Table 2—

Cardiovascular variables recorded at various times during the surgical procedure in the cats in Table 1.

VariableTreatment groupT0T1T2T3T4T5T6T7
Heart rate (beats/min)Remifentanil-ketamine115 ± 27109 ± 25142 ± 47152 ± 26163 ± 26144 ± 32182 ± 50*199 ± 43*
 Remifentanil128 ± 30128 ± 32162 ± 33152 ± 14170 ± 40144 ± 29161 ± 45154 ± 28
 Control125 ± 23127 ± 14161 ± 41173 ± 43*182 ± 44*179 ± 38*174 ± 45171 ± 42
SBP (mm Hg)         
 Remifentanil-ketamine64 ± 1263 ± 12105 ± 44*102 ± 25101 ± 3280 ± 16105 ± 37112 ± 35*
 Remifentanil72 ± 1672 ± 1192 ± 30*102 ± 2384 ± 2280 ± 2392 ± 2490 ± 24
 Control72 ± 2268 ± 17101 ± 4496 ± 3997 ± 4284 ± 2184 ± 2392 ± 27
Spo2 (%)         
 Remifentanil-ketamine97 ± 396 ± 396 ± 297 ± 297 ± 298 ± 197 ± 197 ± 1
 Remifentanil97 ± 297 ± 397 ± 398 ± 297 ± 298 ± 297 ± 297 ± 2
 Control98 ± 297 ± 297 ± 196 ± 198 ± 297 ± 197 ± 196 ± 1
Respiratory rate (breaths/min)         
 Remifentanil-ketamine12 ± 212 ± 212 ± 212 ± 112 ± 212 ± 212 ± 214 ± 7
 Remifentanil12 ± 212 ± 212 ± 212 ± 212 ± 212 ± 212 ± 212 ± 2
 Control12 ± 214 ± 315 ± 513 ± 215 ± 514 ± 413 ± 314 ± 4
Petco2 (mm Hg)         
 Remifentanil-ketamine29 ± 527 ± 729 ± 628 ± 629 ± 628 ± 529 ± 628 ± 6
 Remifentanil24 ± 623 ± 625 ± 425 ± 324 ± 222 ± 423 ± 425 ± 7
 Control28 ± 327 ± 427 ± 428 ± 328 ± 427 ± 526 ± 426 ± 4
Esophagea temperature (°C)         
 Remifentanil-ketamine38.2 ± 0.638.1 ± 0.638.0 ± 0.637.7 ± 0.6*37.6 ± 0.7*37.4 ± 0.7*37.4 ± 0.7*37.3 ± 0.7*
 Remifentanil37.7 ± 1.237.5 ± 1.237.4 ± 1.1*37.3 ± 0.9*37.0 ± 0.8*36.9 ± 0.9*36.9 ± 0.7*36.8 ± 0.7*
 Control37.6 ± 0.537.4 ± 0.5*37.3 ± 0.4*37.2 ± 0.3*37.0 ± 0.3*36.9 ± 0.3*36.8 ± 0.4*36.8 ± 0.4*

Data are given as mean ± SD. Data were recorded at baseline immediately before the beginning of the skin incision (T0), at the end of the celiotomy (T1), during traction and ligation of the left ovarian pedicle (T2), during traction and ligation of the right ovarian pedicle (T3), during hysterectomy (T4), at the mid-point of the abdominal closure (T5), at the mid-point of the subcutaneous closure (T6), and at the mid-point of the intradermal closure (T7).

Significantly (P < 0.05) different from baseline (T0) value.

See Table 1 for remainder of key.

Mean ETiso for cats in the remifentanil-ketamine group (mean ± SD, 0.63 ± 0.4%) was significantly (P = 0.006) lower than mean ETiso for cats in the control group (1.22 ± 0.5%) but was not significantly (P = 0.078) different from mean ETiso for cats in the remifentanil group (1.03 ± 0.4%). Mean ETiso for cats in the remifentanil group was not significantly (P = 0.810) different from mean ETiso for cats in the control group. When data for specific time points during the surgical procedure were compared among groups, mean ETiso was significantly lower for cats in the remifentanil-ketamine group than for cats in the control group at T0 (P = 0.029), T1 (P = 0.004), T2 (P = 0.018), T3 (P = 0.040), and T5 (P = 0.019; Figure 1). Compared with cats in the control group, isoflurane requirement was reduced by a mean of 48.3% (range, 28.2% to 61.5%) for cats in the remifentanil-ketamine group and by a mean of 15.6% (range, 4.9% to 29.5%) for cats in the remifentanil group.

Figure 1—
Figure 1—

Mean ± SD ETiso in healthy cats undergoing elective ovariohysterectomy that were anesthetized with isoflurane and given CRIs of remifentanil and ketamine (closed circles; n = 7), remifentanil alone (triangles; 8), or crystalloid fluids alone (control group [open circles]; 8). Data were recorded at baseline immediately before the beginning of the skin incision (T0), at the end of the celiotomy (T1), during traction and ligation of the left ovarian pedicle (T2), during traction and ligation of the right ovarian pedicle (T3), during hysterectomy (T4), at the mid-point of the abdominal closure (T5), at the mid-point of the subcutaneous closure (T6), and at the mid-point of the intradermal closure (T7). 1Significantly (P < 0.05) different from values for cats in the control group.

Citation: Journal of the American Veterinary Medical Association 246, 9; 10.2460/javma.246.9.976

Discussion

Results of the present study indicated that at the doses administered, CRIs of remifentanil and ketamine resulted in a significant decrease in the isoflurane requirement in healthy cats undergoing elective ovariohysterectomy, compared with the isoflurane requirement for control cats, without affecting the quality of anesthetic recovery. However, providing CRIs of both remifentanil and ketamine did not result in a significant reduction in the isoflurane requirement, compared with the isoflurane requirement for cats that received a CRI of remifentanil alone. Although only healthy cats were used in the present study, we speculate that the isoflurane-sparing effect of remifentanil-ketamine CRIs may be important in ill cats that do not tolerate isoflurane-induced adverse effects, such as cardiorespiratory depression.9

In a previous study,8 administering ketamine as a bolus (2 mg/kg [0.9 mg/lb]) followed by a CRI (1.38 mg/kg/h [0.63 mg/lb/h]) reduced the mean MAC of isoflurane in cats by 45%, which is similar to the mean 48.3% decrease in isoflurane requirement observed in the present study among cats given CRIs of both remifentanil and ketamine. Although we did not identify a significant difference in isoflurane requirement between the remifentanil-ketamine and remifentanil groups, we believe that ketamine played an important role in reducing the isoflurane requirement. However, because we did not include a group receiving only a ketamine infusion, it was not possible to identify the magnitude of any interaction between remifentanil and ketamine. Ketamine has been advocated for patients with neuropathic or chronic pain,10 and it is possible that it provided a benefit by preventing central sensitization in the present study. Previous studies11,12 have shown that ketamine induces long-acting analgesia in dogs undergoing major surgery when combined with opioids and other analgesic techniques. Optimal pain relief is often difficult to achieve without clinically important adverse effects when using a single analgesic, such as an opioid, and this is why multimodal analgesia is typically recommended.13 However, the present study was designed only to evaluate the anesthetic effects, and not the analgesic effects, of remifentanil and ketamine CRIs in cats undergoing ovariohysterectomy. Thus, we cannot draw any conclusions regarding whether ketamine provided analgesia in this study.

In the present study, the isoflurane-sparing effects in cats given remifentanil and ketamine CRIs were not accompanied by significant improvements in SBP or heart rate, compared with values for cats in the control group. Remifentanil and ketamine infusions have been shown to induce sympathetic stimulation in cats, resulting in increases in heart rate and blood pressure.4,8 Potentially, therefore, these drugs could minimize the negative inotropic effects and reductions in blood pressure associated with inhalation anesthetics, but this was not observed in our study. A possible explanation would be that in our study, inspired isoflurane concentrations were altered on the basis of subjective assessments of anesthetic depth, including jaw tone, palpebral reflexes, eye position, and response to instrumentation and surgery, which could have differed among treatment groups. Temporal changes in heart rate, SBP, and esophageal temperature were expected owing to different degrees of nociceptive stimulation during surgery and cooling of the patient.

Anesthetic recovery following prolonged ketamine or remifentanil infusions have been reported to be rough and protracted,4,8 which was not the case in the present study. However, in those previous studies, cats were anesthetized for up to 12 hours, with sequential increases in infusion rates during determination of the MAC of isoflurane. Results of the present study indicated that short-term administration of a remifentanil CRI, with or without ketamine, does not affect anesthetic recovery scores at the dosages described. The same finding was observed when similar dosages of remifentanil were administered to cats undergoing ovariohysterectomy that were anesthetized with propofol.14,15 The administration of acepromazine and a pain-free recovery might also explain the good recovery quality in the present study.

In cats, remifentanil has a rapid onset and short duration of action with rapid clearance.3 In the present study, a CRI of remifentanil alone was not associated with a significant decrease in mean isoflurane requirement, even though isoflurane requirement was reduced by a mean of 15.6% for cats in the remifentanil group, compared with the requirement for cats in the control group. This was not surprising, given that opioid-induced reductions in the MAC of isoflurane in cats are reportedly of limited magnitude.4,5 In 1 study,4 remifentanil CRIs (15, 30, and 60 μg/kg/h [6.82, 13.64, and 27.27 μg/lb/h]) decreased the MAC of isoflurane by up to 30%. Increasing doses did not cause further reductions, indicating that a ceiling effect for MAC reduction was achieved at 15 μg/kg/h. Therefore, it is unlikely that increasing the dosages used in our study would lead to significantly greater, clinically relevant isoflurane-sparing effects. Furthermore, a different study5 did not show significant changes in the MAC of isoflurane after administration of a remifentanil CRI, but did demonstrate thermal antinociception. This could imply that remifentanil provided analgesia in the present study even without causing a significant change in the isoflurane requirement. Importantly, studies of the MAC of inhalation anesthetics involve gross movement in response to a noxious stimulus as an end point. In the present study, isoflurane requirements were adjusted on the basis of autonomic responses during surgery, and it is not clear how these observations correlate with MAC.

It is difficult to explain why the mean dose of propofol used for anesthetic induction was significantly higher for cats in the remifentanil-ketamine group than for cats in the control group in the present study. Four cats in remifentanil-ketamine group required doses of propofol > 8.2 mg/kg (3.73 mg/lb) to allow endotracheal intubation, and 2 of these cats could be intubated only after administration of 10 mg of propofol/kg (4.55 mg/lb). Some cats were not adequately sedated after premedication, and perhaps acepromazine and morphine had little, if any, effect in reducing the propofol requirement for anesthetic induction in these individuals. Higher doses of propofol may have been required owing to individual variations in age, body weight, behavior, and the intrinsic pharmacokinetic and pharmacodynamics variations of the drug. The significantly higher mean dose of propofol for cats in the remifentanil-ketamine group could be considered a confounding factor, in that propofol might have decreased the isoflurane requirement, especially at early time points.

In conclusion, the present study found that a combination of remifentanil and ketamine CRIs can be used clinically to decrease the amount of isoflurane required for anesthetic maintenance in cats without affecting anesthetic recovery. Given the clinically relevant isoflurane-sparing effect, this combination may be a better choice for balanced anesthesia in feline clinical practice.

ABBREVIATIONS

CRI

Constant rate infusion

ETISO

End-tidal concentration of isoflurane

MAC

Minimum alveolar concentration

PETCO2

End-tidal partial pressure of carbon dioxide

SBP

Systolic arterial blood pressure

SpO2

Oxygen saturation as measured by pulse oximetry

a.

Research Randomizer, version 4.0. Available at: www.randomizer.org. Accessed Jan 19, 2015.

b.

Isoflurane USP, Pharmaceutical Partners of Canada, Richmond Hill, ON, Canada.

c.

Tech 4 Anesthesia Vaporiser, Dispomed, Joliette, QC, Canada.

d.

Moduflex Coaxial, Dispomed, Joliette, QC, Canada.

e.

Lifewindow LW6000, Digicare Biomedical Technology, Boynton Beach, Fla.

f.

T/Pump Classic, Matvet Inc, Orchard Park, NY.

g.

Hallowell model 2000, Pittsfield, Mass.

h.

Ultrasonic Doppler Flow Detector, Parks Medical Electronics Inc, Aloha, Ore.

i.

Remifentanil, Novopharm Ltd, Toronto, ON, Canada.

j.

Vetalar, Bioniche Animal Health Canada Inc, Belle Ville, ON, Canada.

k.

Baxter Colleague, Deerfield, Ill.

l.

Graseby syringe pump 3400, Smiths Medical ASD Inc, Saint Paul, Minn.

m.

SPSS Statistics for Windows, version 20.0, IBM Corp, Armonk, NY.

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