Cardiopulmonary effects of an intravenous infusion of fentanyl in cats during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery

Stephanie C. J. Keating Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

Search for other papers by Stephanie C. J. Keating in
Current site
Google Scholar
PubMed
Close
 DVM, DVSc
and
Carolyn L. Kerr Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

Search for other papers by Carolyn L. Kerr in
Current site
Google Scholar
PubMed
Close
 DVM, DVSc, PhD

Abstract

OBJECTIVE

To determine the cardiopulmonary effects of IV administration of fentanyl to cats anesthetized with isoflurane and during anesthetic recovery with concurrent administration of acepromazine or dexmedetomidine.

ANIMALS

6 healthy adult cats.

PROCEDURES

Cats received an IV bolus (5 μg/kg) followed by an IV infusion (5 μg/kg/h) of fentanyl for 120 minutes during isoflurane anesthesia and for 30 minutes after discontinuing isoflurane. Cats were randomly assigned in a crossover study to receive acepromazine (0.05 mg/kg) or dexmedetomidine (2.5 μg/kg), IV, when isoflurane was discontinued. Cardiopulmonary data were obtained during anesthesia and for 30 minutes during the anesthetic recovery period.

RESULTS

The administration of fentanyl during isoflurane anesthesia resulted in a transient increase in arterial blood pressure, mean pulmonary artery pressure, and oxygen delivery. Compared with values during isoflurane anesthesia, administration of dexmedetomidine during anesthetic recovery resulted in significant decreases in cardiac index, stroke index, and oxygen delivery and significant increases in arterial, central venous, and mean pulmonary artery pressures; systemic vascular resistance index; and oxygen extraction ratio. Administration of acepromazine resulted in increases in heart rate, cardiac index, oxygen uptake, and oxygen extraction ratio. Oxygen extraction ratio did not differ between acepromazine and dexmedetomidine.

CONCLUSIONS AND CLINICAL RELEVANCE

Fentanyl transiently improved indices of cardiopulmonary performance when administered to healthy cats anesthetized with isoflurane. The cardiovascular effects of acepromazine and dexmedetomidine in healthy cats receiving fentanyl during recovery from isoflurane anesthesia differed, but measured cardiopulmonary parameters remained within acceptable limits.

Abstract

OBJECTIVE

To determine the cardiopulmonary effects of IV administration of fentanyl to cats anesthetized with isoflurane and during anesthetic recovery with concurrent administration of acepromazine or dexmedetomidine.

ANIMALS

6 healthy adult cats.

PROCEDURES

Cats received an IV bolus (5 μg/kg) followed by an IV infusion (5 μg/kg/h) of fentanyl for 120 minutes during isoflurane anesthesia and for 30 minutes after discontinuing isoflurane. Cats were randomly assigned in a crossover study to receive acepromazine (0.05 mg/kg) or dexmedetomidine (2.5 μg/kg), IV, when isoflurane was discontinued. Cardiopulmonary data were obtained during anesthesia and for 30 minutes during the anesthetic recovery period.

RESULTS

The administration of fentanyl during isoflurane anesthesia resulted in a transient increase in arterial blood pressure, mean pulmonary artery pressure, and oxygen delivery. Compared with values during isoflurane anesthesia, administration of dexmedetomidine during anesthetic recovery resulted in significant decreases in cardiac index, stroke index, and oxygen delivery and significant increases in arterial, central venous, and mean pulmonary artery pressures; systemic vascular resistance index; and oxygen extraction ratio. Administration of acepromazine resulted in increases in heart rate, cardiac index, oxygen uptake, and oxygen extraction ratio. Oxygen extraction ratio did not differ between acepromazine and dexmedetomidine.

CONCLUSIONS AND CLINICAL RELEVANCE

Fentanyl transiently improved indices of cardiopulmonary performance when administered to healthy cats anesthetized with isoflurane. The cardiovascular effects of acepromazine and dexmedetomidine in healthy cats receiving fentanyl during recovery from isoflurane anesthesia differed, but measured cardiopulmonary parameters remained within acceptable limits.

Introduction

Fentanyl is a short-acting full μ-opioid receptor agonist that provides effective and sustained analgesia when administered as an IV infusion following an initial loading dose.1,2 Administration of fentanyl and other short-acting opioids to cats during general anesthesia blunts autonomic and humoral responses to noxious stimuli and can reduce inhalational anesthetic requirements, which may subsequently improve hemodynamic performance.3,4 In addition to intraoperative administration, an IV infusion of fentanyl is often continued into the anesthetic recovery period to provide ongoing analgesia.5

The physiologic effects of full μ-opioid receptor agonists vary depending on the species but are generally well tolerated. The cardiopulmonary effects of fentanyl have been studied6–8 extensively in dogs, with the most notable effect being a decrease in HR that is primarily mediated through enhanced vagal outflow, with secondary contributions from local potentiation of vagal activity, suppression of sympathetic outflow, and direct negative chronotropic effects on the sinoatrial node. When fentanyl is administered to dogs during isoflurane anesthesia, HR, CO, and RR significantly decrease.9,10 Although the pharmacokinetics and antinociceptive effects of fentanyl administered IV to cats have been evaluated,2,11 the cardiopulmonary effects of fentanyl have not yet been comprehensively characterized.

Less is known about the cardiopulmonary changes in cats during anesthetic recovery, which is a time associated with an increased risk of anesthetic death.12 The phenothiazine acepromazine and the α2-adrenoceptor agonist dexmedetomidine are sedatives that may be administered in the immediate recovery period to mitigate or resolve dysphoria or emergence delirium. The concurrent administration of acepromazine or dexmedetomidine to dogs in the presence of fentanyl and residual isoflurane causes significant cardiopulmonary changes9; however, the effects of the aforementioned combinations have not been described in cats.

The objectives of the study presented here were to characterize the cardiopulmonary effects of fentanyl administered to cats anesthetized with isoflurane and during anesthetic recovery when acepromazine or dexmedetomidine was concurrently administered. We hypothesized that fentanyl would result in a mild increase in hemodynamic performance, including an increase in CI, and mild respiratory depression during anesthesia and speculated that acepromazine and dexmedetomidine would impart different cardiopulmonary effects when administered during anesthetic recovery, with a decrease in CI following dexmedetomidine administration.

Materials and Methods

Animals

Six neutered male purpose-bred domestic shorthair cats that were 1 to 2 years old and weighed 4.74 ± 0.46 kg (mean ± SD) were used in the study. All cats were considered healthy on the basis of the findings from the medical history, physical examination, CBC, and serum biochemical analysis. Food was withheld for 12 hours prior to each anesthetic event; however, cats had free access to water during the study period. The study was approved by the Institutional Animal Care Committee at the University of Guelph (protocol No. 3752).

Study design

A randomized crossover study design was used, with each cat randomizeda to receive acepromazineb (0.05 mg/kg) or dexmedetomidinec (2.5 μg/kg) on recovery from anesthesia. A minimum 7-day washout period elapsed between anesthetic events.

Instrumentation

For each event, a 22-gauge, over-the-needle catheterd was inserted into one of the cephalic veins. Anesthesia was then induced with propofole administered IV to effect, and cats were orotracheally intubated. Anesthesia was maintained with isofluranef (1.5% to 2.0%) delivered in oxygen at a flow rate of 200 mL/kg/min with a Bain circuit. A side-stream capnograph was placed between the endotracheal tube and the Bain circuit to measure end-tidal partial pressure of CO2 and isoflurane concentration. A 22-gauge, over-the-needle catheterd was also inserted into one of the dorsal pedal arteries for invasive arterial blood pressure measurement and collection of arterial blood samples. A 5F introducerg was then placed into one of the jugular veins, and a 4F thermodilution catheterh was inserted through the introducer and positioned with the distal port in the pulmonary artery. Correct placement was verified by fluoroscopy and pressure waveform analysis. The arterial and pulmonary artery catheters were each connected to a blood pressure transducer by low compliant tubingi and connected to a multiparameter monitor.j All blood pressure transducers were zeroed to atmospheric pressure and leveled at the manubrium. Respiratory rate was measured by counting thoracic excursions over a 30-second period. Heart rate was recorded as displayed by the multiparameter monitor invasive blood pressure pulse rate, ensuring there was a clear pressure waveform and a stable reading before recording each value. All cardiovascular variables were displayed on the multiparameter monitor.

Study protocol

After instrumentation, each cat was positioned in left or right lateral recumbency with the pulmonary catheter facing upward, and each cat was allowed to breath spontaneously. A forced air warmerk was applied to maintain a core temperature between 37°C and 38.5°C, and a balanced electrolyte solutionl was administered at 3 mL/kg/h throughout the experimental period. The vaporizer setting on the anesthetic machine was adjusted to achieve an end-tidal isoflurane concentration of 1.5%, which remained stable for 15 minutes prior to baseline data collection.

Variables recorded at each time point included end-tidal isoflurane concentration, core body temperature, HR, SAP, DAP, MAP, CVP, MPAP, CO, and RR. The pulmonary artery catheter was used to obtain measurements of core body temperature, CVP, MPAP, and CO. Cardiac output was measured in triplicate following rapid injection of 3 mL of 5% dextrose solution at 1°C to 2°C. Values of CO within 15% of each other were averaged to obtain the mean value for that time point.

On the basis of the recorded measurements for some of these parameters, CI, SI, SVRI, D˙2, V˙o2, and O2ER were calculated by use of the following formulas13:

article image

where BW is the body weight (kg);

article image

where 79.9 is the conversion factor for mm Hg•min/L to dynes•s/cm5;

article image

where CaO2 = ([1.39 × Hb × Sao2] + [0.0031 × Pao2]) × 10, in which Hb is hemoglobin (g/dL), Sao2 is arterial oxygen saturation, and 0.0031 is the solubility of O2 in whole blood (vol%/mm Hg); and

article image

where CvO2 = ([1.39 × Hb × Pv¯o2] + [0.0031 × Pv¯o2]) × 10 and Sv¯o2 is mixed venous oxygen saturation.

For each time point, 3 mL of mixed venous blood were withdrawn from the distal port of the pulmonary artery catheter, an additional 1 mL was then withdrawn for analysis, and the initial 3 mL was returned through the same catheter. A similar procedure was used for collecting arterial blood samples from the dorsal pedal artery catheter at each time point, but only 1 mL was withdrawn prior to sample collection and then returned. Blood samples were immediately analyzed by an automated analyzerm for the determination of blood gases, pH, and hemoglobin, glucose, and lactate concentrations.

After baseline data collection, a bolus of fentanyln was administered IV at 5 μg/kg over 60 seconds, followed immediately by an IV constant rate infusion of fentanyl at 5 μg/kg/h for 120 minutes during isoflurane anesthesia and for 30 minutes after discontinuing isoflurane. Data were collected at 5, 10, 15, 30, 60, and 120 minutes after beginning fentanyl administration during isoflurane anesthesia. After discontinuation of isoflurane, each cat was immediately administered acepromazine or dexmedetomidine IV. Fentanyl administration was continued for 30 minutes into the anesthetic recovery period. Additional data were then collected at 5, 10, 15, and 30 minutes after administration of acepromazine or dexmedetomidine. After the experimental period, all instrumentation was removed and each cat was administered meloxicamo (0.1 mg/kg, IV) and cefazolinp (22 mg/kg, IV).

Statistical analysis

Data for the anesthetic maintenance phase and recovery phase were analyzed separately. Data were assessed for normality with the Shapiro-Wilk test and analysis of the residuals. Log transformation was applied to the data, if necessary, to transform skewed data to approximately conform to normality, thereby allowing the use of parametric tests. Then, ANOVA for repeated measures was performed to evaluate the effects of treatment, time, and treatment by time interactions as well as any carryover effect from the previous treatment. Post hoc analyses were performed with Dunnett and Tukey procedures. All statistical analyses were performed with a statistical software program.q Values of P < 0.05 were considered significant.

Results

Data for the anesthetic maintenance phase (isoflurane and fentanyl) were pooled between acepromazine or dexmedetomidine treatments because no treatment or carryover effects were evident for any variable during this phase. Results for the cardiopulmonary and hematologic parameters that were obtained during isoflurane and fentanyl anesthesia are summarized (Table 1). Five minutes after the beginning of fentanyl administration, significant but transient increases (vs baseline) were noted for DAP, MAP, D˙2, and hemoglobin and lactate concentrations. For the first 10 to 15 minutes after fentanyl administration, SAP, MPAP, and CI were significantly increased (vs baseline). At all time points, glucose concentrations were significantly increased (vs baseline).

Table 1

Cardiopulmonary and hematologic parameters (mean ± SD) for 6 healthy adult cats that were anesthetized with isoflurane; data were obtained before (baseline) and at various time points (minutes) during fentanyl administration (5 μg/kg, IV, [bolus], then immediately 5 μg/kg/h, IV).

Parameter Baseline Time (min)
5 10 15 30 60 120
HR (beats/min) 141 ± 22 163 ± 43 170 ± 47 153 ± 47 148 ± 38 136 ± 27 158 ± 42
SAP (mm Hg) 94 ± 16 118 ± 22* 114 ± 20* 102 ± 20 106 ± 15 104 ± 15 111 ± 20*
DAP (mm Hg) 54 ± 8 70 ± 19* 60 ± 11 52 ± 9 54 ± 7 53 ± 6 59 ± 11
MAP (mm Hg) 67 ± 9 85 ± 19* 77 ± 15 69 ± 12 69 ± 9 67 ± 6 75 ± 12
CVP (mm Hg) 8 ± 4 8 ± 3 9 ± 3 9 ± 3 8 ± 3 8 ± 4 8 ± 4
MPAP (mm Hg) 16 ± 3 20 ± 4* 22 ± 5* 21 ± 6* 16 ± 4 17 ± 3 17 ± 4
CI (mL/kg/min) 116 ± 20 144 ± 33* 140 ± 29* 136 ± 26 124 ± 19 118 ± 19 124 ± 23
SI (mL/kg/beat) 0.84 ± 0.16 0.90 ± 0.16 0.85 ± 0.18 0.88 ± 0.18 0.87 ± 0.17 0.88 ± 0.15 0.81 ± 0.17
SVRI (dynes•s/cm5/kg) 1,781 ± 436 1,946 ± 459 1,818 ± 382 1,630 ± 330 1,795 ± 378 1,808 ± 353 1,991 ± 438
RR (breaths/min) 30 ± 13 31 ± 10 35 ± 14 34 ± 13 29 ± 12 24 ± 8 31 ± 16
Pao2 (mm Hg) 454.0 ± 28.6 454.5 ± 33.2 439.3 ± 43.8 441.8 ± 30.3 437.7 ± 55.3 450.4 ± 37.5 462.7 ± 38.0
Paco2 (mm Hg) 39.1 ± 4.1 39.9 ± 6.5 40.6 ± 5.9 41.0 ± 5.7 41.3 ± 6.7 42.4 ± 6.9 41.4 ± 9.1
Arterial pH 7.314 ± 0.038 7.306 ± 0.050 7.296 ± 0.045 7.295 ± 0.045 7.289 ± 0.063 7.295 ± 0.054 7.316 ± 0.065
Pv¯o2 (mm Hg) 64.5 ± 6.8 67.8 ± 10.7 67.0 ± 10.3 69.8 ± 13.3 69.1 ± 11.1 70.3 ± 12.6 66.5 ± 12.3
D˙2 (mL/min/kg) 18.0 ± 3.5 23.3 ± 6.7* 20.7 ± 5.9 19.6 ± 4.9 17.4 ± 3.9 16.3 ± 2.8 18.7 ± 3.5
V˙o2 (mL/min/kg) 3.7 ± 1.6 5.2 ± 3.3 5.0 ± 3.1 4.4 ± 1.8 3.6 ± 1.5 3.2 ± 1.2 5.1 ± 2.4
O2ER 0.21 ± 0.09 0.21 ± 0.09 0.23 ± 0.10 0.22 ± 0.08 0.20 ± 0.07 0.20 ± 0.08 0.26 ± 0.09
Hemoglobin (g/dL) 9.8 ± 0.9 10.5 ± 1.2* 9.8 ± 1.3 9.4 ± 0.9 9.0 ± 1.2 8.9 ± 0.9 10.0 ± 0.9
Blood glucose (mmol/L) 7.7 ± 2.5 9.5 ± 2.5* 11.7 ± 2.3* 13.7 ± 1.9* 13.4 ± 2.0* 13.5 ± 2.1* 11.6 ± 2.5*
Lactate (mmol/L) 0.8 ± 0.3 0.9 ± 0.2* 0.8 ± 0.2 0.8 ± 0.2 0.7 ± 0.2 0.6 ± 0.2 0.7 ± 0.2

Value is significantly (P < 0.05) different from baseline.

Results for the cardiopulmonary and hematologic parameters obtained at the anesthetic recovery phase (after discontinuation of isoflurane) during continuation of fentanyl administration and after administration of acepromazine or dexmedetomidine are summarized (Table 2). Compared with values during isoflurane anesthesia, cats that received dexmedetomidine during anesthetic recovery had significant increases in SAP, DAP, MAP, MPAP, SVR, O2ER, and blood glucose concentrations and significant decreases in CI, SI, Pao2, Pv¯o2, and D˙2 for all time points. Compared with values during isoflurane anesthesia, cats that received acepromazine had significant increases in CI, V˙o2, O2ER, and blood glucose concentrations and significant decreases in Pao2 and Pvo2 for all time points. Compared with dexmedetomidine, acepromazine administration resulted in higher HR, CI, and arterial pH and lower DAP, MAP, SVR, and Paco2 for most or all time points during the anesthetic recovery period. Formalized sedation scoring was not performed during anesthetic recovery; however, all cats remained recumbent and required little to no restraint during the data collection period.

Table 2

Cardiopulmonary and hematologic parameters (mean ± SD) for the cats of Table 1 before (Iso) and at various time points (minutes) after isoflurane administration was discontinued, during which fentanyl administration was continued, and after either acepromazine (A; 0.05 mg/kg, IV) or dexmedetomidine (D; 2.5 μg/kg, IV) was administered.

Parameter Treatment Iso Time (min)
5 10 15 30
HR (beats/min) A 158 ± 45 212 ± 58* 228 ± 29* 221 ± 21* 208 ± 21
D 158 ± 43 108 ± 22 105 ± 9 111 ± 21 132 ± 60
SAP (mm Hg) A 110 ± 23 140 ± 36 131 ± 24 121 ± 21 126 ± 5
D 113 ± 17 212 ± 42* 189 ± 41* 175 ± 34* 161 ± 12*
DAP (mm Hg) A 57 ± 11 81 ± 19 85 ± 8 76 ± 10 76 ± 11
D 62 ± 12 145 ± 15* 132 ± 18* 124 ± 16* 112 ± 8*
MAP (mm Hg) A 72 ± 13 96 ± 19 96 ± 10 90 ± 10 90 ± 10
D 78 ± 13 168 ± 22* 153 ± 26* 143 ± 23* 130 ± 7*
CVP (mm Hg) A 8 ± 4 8 ± 5 6 ± 3 7 ± 5 8 ± 4
D 8 ± 4 14 ± 2* 13 ± 2* 12 ± 2 10 ± 2
MPAP (mm Hg) A 18 ± 5 20 ± 4 25 ± 2 25 ± 7 17 ± 5
D 16 ± 3 29 ± 6* 27 ± 7* 27 ± 5* 28 ± 11*
CI (mL/kg/min) A 122 ± 28 156 ± 25* 170 ± 41* 158 ± 20* 151 ± 14*
D 126 ± 21 69 ± 13* 73 ± 15* 75 ± 14* 89 ± 16*
SI (mL/kg/beat) A 0.79 ± 0.17 0.70 ± 0.12 0.74 ± 0.11 0.72 ± 0.07 0.73 ± 0.09
D 0.83 ± 0.18 0.66 ± 0.16* 0.70 ± 0.15* 0.69 ± 0.16* 0.75 ± 0.21*
SVRI (dynes•s/cm5/kg) A 1,943 ± 576 1,723 ± 417 2,024 ± 416 1,760 ± 315 1,776 ± 381
D 2,049 ± 240 8,077 ± 1,680* 7,144 ± 1,906* 6,331 ± 1,438* 4,922 ± 933*
RR (breaths/min) A 30 ± 16 25 ± 7 25 ± 4 24 ± 6 23 ± 8
D 31 ± 17 27 ± 6 28 ± 4 26 ± 6 25 ± 5
Pao2 (mm Hg) A 457.5 ± 45.4 104.2 ± 20.7* 117.1 ± 22.3* 103.7 ± 20.3* 97.1 ± 5.4*
D 469.0 ± 30.6 95.7 ± 14.0* 90.7 ± 12.3* 94.1 ± 16.3* 95.3 ± 21.9*
Paco2 (mm Hg) A 40.9 ± 7.3 38.3 ± 5.8 37.2 ± 5.1 38.0 ± 7.5 36.6 ± 5.0
D 42.0 ± 11.7 44.6 ± 5.6 45.3 ± 6.2 44.8 ± 5.9 43.2 ± 6.9
Arterial pH A 7.314 ± 0.048 7.315 ± 0.027 7.312 ± 0.028 7.311 ± 0.049 7.330 ± 0.042
D 7.318 ± 0.087 7.272 ± 0.038 7.265 ± 0.044 7.270 ± 0.045 7.273 ± 0.059
Pv¯o2 (mm Hg) A 64.2 ± 8.7 48.4 ± 8.2* 45.4 ± 3.0* 45.8 ± 2.6* 43.7 ± 5.2*
D 69.3 ± 16.3 45.1 ± 4.2* 47.6 ± 6.1* 45.7 ± 3.9* 44.2 ± 3.5*
D˙2 (mL/min/kg) A 18.1 ± 3.4 24.2 ± 7.6 23.1 ± 7.2 21.8 ± 4.6 22.4 ± 1.9
D 19.5 ± 3.9 11.7 ± 2.8* 11.5 ± 2.9* 11.6 ± 2.6* 13.4 ± 3.1*
V˙o2 (mL/min/kg) A 5.0 ± 2.2 9.8 ± 7.9* 7.2 ± 6.9* 7.1 ± 4.3* 8.9 ± 5.0*
D 5.2 ± 2.9 5.4 ± 0.8 4.6 ± 0.6 4.9 ± 0.7 5.9 ± 1.6
O2ER A 0.27 ± 0.09 0.46 ± 0.12* 0.45 ± 0.08* 0.38 ± 0.06* 0.48 ± 0.09*
D 0.26 ± 0.11 0.47 ± 0.07* 0.41 ± 0.10* 0.43 ± 0.10* 0.44 ± 0.05*
Hemoglobin (g/dL) A 9.8 ± 0.8 11.0 ± 1.6* 10.3 ± 1.4 9.9 ± 1.2 10.6 ± 0.5
D 10.2 ± 1.0 12.2 ± 1.1* 11.6 ± 0.5* 11.1 ± 0.2 11.2 ± 1.0
Blood glucose (mmol/L) A 11.3 ± 3.3 12.8 ± 3.1* 13.7 ± 2.5* 15.0 ± 2.2* 13.9 ± 2.7*
D 11.9 ± 1.6 13.2 ± 1.6* 15.9 ± 1.8* 17.4 ± 1.7* 16.5 ± 1.9*
Lactate (mmol/L) A 0.7 ± 0.2 1.4 ± 0.8* 1.4 ± 0.7* 1.2 ± 0.5 1.4 ± 0.6
D 0.6 ± 0.3 0.8 ± 0.3 0.8 ± 0.2 0.7 ± 0.2 1.6 ± 1.3

Value is significantly (P < 0.05) different from Iso.

Value is significantly (P < 0.05) different between treatments.

Discussion

The administration of fentanyl as an IV bolus and constant rate infusion to healthy cats that were anesthetized with isoflurane resulted in a transient period of increased hemodynamic performance without a significant effect on respiratory variables. The observed changes were significant 5 to 15 minutes after the start of fentanyl administration and were likely attributable to higher plasma fentanyl concentrations attained soon after bolus administration, as values returned to baseline during the fentanyl infusion. The cardiovascular effects were most notably characterized by an increase in arterial blood pressure and CI. Although HR and SI did not significantly differ at any time point, compared with baseline values, increases in HR paralleled increases in CI, suggesting that HR was the likely cause of increased CI.

Similar signs of sympathetic stimulation have been reported with the administration of other full μ-opioid receptor agonists in healthy cats.3,14,15 Administration of remifentanil, alfentanil, and sufentanil to healthy cats has been reported3,14,15 to cause increases in body temperature, systemic and pulmonary arterial pressures, HR, CI, SI, Pv¯o2, and Pv¯co2, with minimal change in RR. These changes are associated with an increase in circulating catecholamine and cortisol concentration, suggesting they are secondary to the stimulatory effects of the opioid, rather than solely from the cardiovascular-sparing effects of isoflurane reduction imparted by opioid administration.3,16 These hemodynamic changes also occur without a reduction in inhalational anesthetic delivery,15 as observed in the present study, further corroborating that conclusion.

The autonomic changes and subsequent cardiovascular responses from administration of full μ-opioid receptor agonists vary depending on the species. Sympathetic stimulation also predominates after fentanyl administration to awake17 and anesthetized18 horses, as evidenced by increases in blood pressure and HR. This is in contrast to the cardiopulmonary effects of fentanyl administration in dogs. A previous study9 evaluating the effects of fentanyl administration during isoflurane anesthesia in dogs included methodology similar to that of the present study, allowing for a more direct species comparison. Fentanyl administration to those dogs resulted in significant decreases in HR, CI, and arterial blood pressure as well as apnea and mild respiratory acidosis in many dogs,9 none of which were observed in the cats of the present study. The cardiovascular effects in dogs may be the result of increased vagal outflow and suppression of sympathetic tone.6–9 In awake dogs and cats, 40 μg of fentanyl/kg, IV, induced respiratory depression and cyanosis in all dogs but in no cats.19 Combined, the findings clearly indicate the different physiologic responses to full μ-opioid receptor agonists among different species. The results of the previous study9 of dogs and present study of cats suggested that species differences likely persist during general anesthesia with isoflurane despite the potential for additional respiratory depression when opioids are combined with inhalational anesthetics.

Sedatives may need to be administered to dogs and cats during anesthetic recovery to mitigate or resolve opioid-induced dysphoria or emergence delirium. Given the potential need for sedatives in the postanesthetic period and that the postanesthetic period is the time associated with the greatest risk of anesthetic death,12 the cardiopulmonary impacts of acepromazine and dexmedetomidine during anesthetic recovery of cats were evaluated in the present study. Acepromazine administration resulted in significantly increased HR and CI but not arterial blood pressure, compared with values during isoflurane anesthesia. Dexmedetomidine administration resulted in bradycardia, although HR was not significantly different from that prior to dexmedetomidine administration, as well as systemic arterial hypertension and a significant decrease in CI, a typical response to α2-adrenoceptor agonists.20 Interestingly, despite a 2-fold increase in mean CI with acepromazine administration, Pv¯o2 and O2ER were similar between treatments, possibly because of significantly higher V˙o2 in acepromazine-treated cats. The cause of the increase in V˙o2 was uncertain but, it may have been secondary to an increase in catecholamine release during emergence from anesthesia. Catecholamine release may have been considerably lower with dexmedetomidine because of α2-adrenoceptor agonist–mediated reductions in sympathetic outflow, such that the same stimulus for increased V˙o2 was not present.21

A mild increase in lactate concentration was noted for cats 5 and 10 minutes after recovery from isoflurane anesthesia concurrent with acepromazine administration. The increase may have been the result of increased circulating catecholamine concentrations.22 Alternatively, it may have been the result of increased CI, tissue perfusion, and lactate mobilization following a period of reduced perfusion during general anesthesia. Lactate concentrations may not have increased for dexmedetomidine-treated cats because of decreased tissue perfusion and lack of lactate mobilization resulting from decreased CI. Despite markedly different hemodynamic profiles between treatments, Pv¯o2 remained at acceptable values for healthy cats and did not differ between treatments, which suggested similarities in tissue oxygen balance. A similar increase in blood glucose concentration was present with both treatments in the anesthetic recovery period, which may be secondary to excitation and associated catecholamine release or the neurohormonal effects of fentanyl as well as to α2-adrenoceptor agonism by dexmedetomidine.23

Although the cardiopulmonary responses to sedative administration during anesthetic recovery are similar between dogs and cats,9 some differences in cats were observed. In both species, acepromazine administered during anesthetic recovery resulted in an increase in HR, MAP, and CI, compared with values during isoflurane anesthesia. The magnitude of increase in CI is markedly greater in dogs,9 resulting from increases in both HR and SI, unlike cats in which an increase in only HR but not SI was noted. In dogs, increases in D˙2 are matched by increases in V˙o2 during recovery, such that O2ER does not change, compared with values during isoflurane anesthesia. In cats administered acepromazine during anesthetic recovery, increases in V˙o2 exceeded that observed in dogs by almost 2-fold, resulting in higher values for O2ER. Although increases in CI were greater in dogs than cats, MAP was considerably lower in dogs throughout the anesthetic recovery period, despite receiving the same dose of acepromazine.9 The reason for this was unclear, but it may have been the result of pharmacokinetic or pharmacodynamic differences between species or greater circulating catecholamine concentrations in cats recovering from combined fentanyl and isoflurane anesthesia.

The cardiopulmonary effects of fentanyl and dexmedetomidine administered during anesthetic recovery were similar between dogs and cats.9 Compared with values immediately prior to anesthetic recovery, dexmedetomidine most notably decreased CI and D˙2 and increased MAP, SVRI, and O2ER in both species. Not only was the trend the same, but indexed values for D˙2, V˙o2, and O2ER were strikingly similar in dogs and cats administered dexmedetomidine during the anesthetic recovery period. Overall, the increase in O2ER for the cats in the present study was of similar magnitude with either acepromazine or dexmedetomidine administration. This is in contrast to dogs, which have increases in O2ER following dexmedetomidine administration and stable O2ER values following acepromazine administration. These findings suggested that acepromazine uniquely reduced the capacity for cats to safely buffer reductions in D˙2 during the anesthetic recovery period.

The similar methodologies for the study9 of dogs and the present study of cats allow the opportunity to directly compare the results between these species. The major difference between the studies was the higher targeted end-tidal isoflurane concentration in cats (1.5%), compared with dogs (1.2%), which was required to ensure an appropriate plane of anesthesia, as determined in a preliminary study, and reflects the greater isoflurane requirement for cats.24 Additionally, higher oxygen flow rates and use of a nonrebreathing circuit in the present study may have resulted in end-tidal isoflurane concentrations that were less accurate (vs dogs). Another difference was the rate of administration of the fentanyl bolus; the bolus was administered over 60 seconds in the present study of cats and over 15 seconds in the study9 of dogs. This difference may have influenced the respiratory effects of the fentanyl bolus; however, the different respiratory responses to fentanyl administration in dogs and cats suggest that species differences largely underlie the observed differences.19 Plasma fentanyl concentrations were also not quantified in the present study, and given the differences in fentanyl disposition between dogs and cats,1,25 plasma concentrations likely differed between species. An additional consideration in interpreting the findings of the present study was that it was performed with healthy cats and the cardiopulmonary effects of the drugs evaluated, particularly fentanyl, have the potential to be different in critically ill cats with hemodynamic alterations or reduced sympathetic reserve. Future studies evaluating these protocols in other patient populations are warranted.

Overall, the findings of the present study of isoflurane-anesthetized healthy cats indicated improved cardiovascular function without respiratory compromise following fentanyl administration. Although acepromazine and dexmedetomidine administration resulted in different cardiopulmonary effects during anesthetic recovery, both were well tolerated in these cats.

Acknowledgments

Funded by the Ontario Veterinary College Pet Trust Fund.

The authors declare that there were no conflicts of interest.

Presented in abstract form at the 25th Annual International Veterinary Emergency & Critical Care Symposium, Washington, DC, September 2019, and Association of Veterinary Anaesthetists Congress Spring Meeting, Dublin, March 2020.

Footnotes

a.

True random number generator, Random.org, Dublin, Ireland. Available at: www.random.org. May 8, 2017.

b.

Atravet, Boehringer Ingelheim (Canada) Ltd, Burlington, ON, Canada.

c.

Dexdomitor, Zoetis Canada Inc, Kirkland, QC, Canada.

d.

Insyte-W, Becton Dickinson Infusion Therapy Systems Inc, Sandy, Utah.

e.

Diprivan 1%, AstraZeneca, Mississauga, ON, Canada.

f.

IsoFlo, Zoetis, Parsippany, NJ.

g.

IntroFlex Percutaneous Sheath Introducer Kit, Edwards Lifesciences LLC, Irvine, Calif.

h.

Swan-Ganz catheter, Edwards Lifesciences LLC, Irvine, Calif.

i.

Transpac IV, ICU Medical Inc, San Clemente, Calif.

j.

S/5 Anesthesia monitor, Datex-Ohmeda, GE Healthcare, Helsinki, Finland.

k.

3M Bair Hugger, Arizant Healthcare Inc, Eden Prairie, Minn.

l.

Plasma-Lyte A, Baxter, Mississauga, ON, Canada.

m.

Critical Care Xpress, Nova Biomedical, Waltham, Mass.

n.

Fentanyl citrate, Sandoz Canada Inc, Boucherville, QC, Canada.

o.

Metacam, Boehringer Ingelheim (Canada) Ltd, Burlington, ON, Canada.

p.

Cefazolin, Apotex Inc, Toronto, ON, Canada.

q.

SAS, version 9.2, SAS Institute Inc, Cary, NC.

References

  • 1.

    Robertson SA, Taylor PM, Sear JW, et al. Relationship between plasma concentrations and analgesia after intravenous fentanyl and disposition after other routes of administration in cats. J Vet Pharmacol Ther 2005;28:8793.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Carrozzo MV, Alcorn J, Ambros B. Effects of two fentanyl constant rate infusions on thermal thresholds and plasma fentanyl concentrations in awake cats. Vet Anaesth Analg 2018;45:831838.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Pascoe PJ, Ilkiw JE, Fisher LD. Cardiovascular effects of equipotent isoflurane and alfentanil/isoflurane minimum alveolar concentration multiple in cats. Am J Vet Res 1997;58:12671273.

    • Search Google Scholar
    • Export Citation
  • 4.

    Yackey M, Ilkiw JE, Pascoe PJ, et al. Effect of transdermally administered fentanyl on the minimum alveolar concentration of isoflurane in cats. Vet Anaesth Analg 2004;31:183189.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Anderson MK, Day TK. Effects of morphine and fentanyl constant rate infusion on urine output in healthy and traumatized dogs. Vet Anaesth Analg 2008;35:528536.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Laubie M, Schmitt H. Action of the morphinometic agent, fentanyl, on the nucleas tractus solitarii and the nucleus ambiguus cardiovascular neurons. Eur J Pharmacol 1980;67:403412.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Flacke JW, Flacke WE, Bloor BC, et al. Effects of fentanyl, naloxone, and clonidine on hemodynamics and plasma catecholamine levels in dogs. Anesth Analg 1983;62:305313.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Loeb JM, Lichtenthal PR, deTarnowsky JM. Parasympathomimetic effects of fentanyl on the canine sinus node. J Auton Nerv Syst 1984;11:9194.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Keating SC, Kerr CL, Valverde A, et al. Cardiopulmonary effects of intravenous fentanyl infusion in dogs during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery. Am J Vet Res 2013;74:672682.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Williamson AJ, Soares JHN, Pavlisko ND, et al. Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog. Vet Anaesth Analg 2017;44:738745.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Ambros B, Alcorn J, Duke-Novakovski T, et al. Pharmacokinetics and pharmacodynamics of a constant rate infusion of fentanyl (5 μg/kg/h) in awake cats. Am J Vet Res 2014;75:716721.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Brodbelt DC, Blissitt KJ, Hammond RA, et al. The risk of death: the confidential enquiry into perioperative small animal fatalities. Vet Anaesth Analg 2008;35:365373.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Boyd CJ, McDonell WN, Valliant A. Comparative hemodynamic effects of halothane and halothane-acepromazine at equipotent doses in dogs. Can J Vet Res 1991;55:107112.

    • Search Google Scholar
    • Export Citation
  • 14.

    Gaumann DM, Yaksh TL, Tyce GM, et al. Sympathetic stimulating effects of sufentanil in the cat are mediated centrally. Neurosci Lett 1988;91:3035.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Brosnan RJ, Pypendop BH, Siao KT, et al. Effects of remifentanil on measures of anesthetic immobility and analgesia in cats. Am J Vet Res 2009;70:10651071.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Wallenstein MC, Wang SC. Mechanism of morphine-induced mydriasis in the cat. Am J Physiol 1979;236:R292R296.

  • 17.

    Kamerling SG, DeQuick DJ, Weckman TJ, et al. Dose-related effects of fentanyl on autonomic and behavioral responses in performance horses. Gen Pharmacol 1985;16:253258.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Thomasy SM, Steffey EP, Mama KR, et al. The effects of IV fentanyl administration on the minimum alveolar concentration of isoflurane in horses. Br J Anaesth 2006;97:232237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Kamata M, Nagahama S, Kakishima K, et al. Comparison of behavioral effects of morphine and fentanyl in dogs and cats. J Vet Med Sci 2012;74:231234.

  • 20.

    Murrell JC, Hellebrekers LJ. Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog. Vet Anaesth Analg 2005;32:117127.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Hogue CW Jr, Talke P, Stein PK, et al. Autonomic nervous system responses during sedative infusions of dexmedetomidine. Anesthesiology 2002;97:592598.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Qvisth V, Hagström-Toft E, Enoksson S, et al. Catecholamine regulation of local lactate production in vivo in skeletal muscle and adipose tissue: role of –adrenoreceptor subtypes. J Clin Endocrinol Metab 2008;93:240246.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Ambrisko TD, Hikasa Y, Sato K. Influence of medetomidine on stress-related neurohormonal and metabolic effects caused by butorphanol, fentanyl, and ketamine administration in dogs. Am J Vet Res 2005;66:406412.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Steffey EP, Howland D Jr. Isoflurane potency in the dog and cat. Am J Vet Res 1977;38:18331836.

  • 25.

    Sano T, Nishimura R, Kanazawa H, et al. Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs. Vet Anaesth Analg 2006;33:266273.

    • Crossref
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 291 0 0
Full Text Views 1246 645 130
PDF Downloads 809 319 24
Advertisement