Epidural anesthesia with bupivacaine, bupivacaine and fentanyl, or bupivacaine and sufentanil during intravenous administration of propofol for ovariohysterectomy in dogs

Tatiana F. Almeida Surgery Department, School of Veterinary Medicine and Zootechnic, University of São Paulo, São Paulo, Brazil.

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Denise T. Fantoni Surgery Department, School of Veterinary Medicine and Zootechnic, University of São Paulo, São Paulo, Brazil.

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Sandra Mastrocinque Surgery Department, School of Veterinary Medicine and Zootechnic, University of São Paulo, São Paulo, Brazil.

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Angelica C. Tatarunas Surgery Department, School of Veterinary Medicine and Zootechnic, University of São Paulo, São Paulo, Brazil.

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Viviane H. Imagawa Surgery Department, School of Veterinary Medicine and Zootechnic, University of São Paulo, São Paulo, Brazil.

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Abstract

Objective—To compare cardiovascular and systemic effects and analgesia during the postoperative period of epidural anesthesia performed with bupivacaine alone or with fentanyl or sufentanil in bitches maintained at a light plane of anesthesia with continuous infusion of propofol.

Study Design—Prospective randomized masked clinical trial.

Animals—30 female dogs of various breeds.

Procedures—Dogs were allocated into 3 groups of 10 each. One group received fentanyl (2 μg/kg [0.91 μg/lb]) and bupivacaine (1 mg/kg [0.45 mg/lb]), 1 group received sufentanil (1 μg/kg) and bupivacaine (1 mg/kg), and 1 group received bupivacaine (1 mg/kg). All dogs received acepromazine (0.1 mg/kg [0.045 mg/lb]) and continuous infusion of propofol for sedation. The agents were administered into the lumbosacral space and diluted in saline (0.9% NaCl) solution to a total volume of 0.36 mL/kg (0.164 mL/lb). Cardiac and respiratory rates, arterial blood pressures, pH, and blood gases were evaluated. Analgesia, sedation level, serum cortisol concentrations, and plasma catecholamine concentrations were measured regularly for 6 hours.

Results—No important changes in cardiovascular, respiratory, or sedation variables were observed. Degree of analgesia in the postoperative period was higher in the sufentanil group, although use of fentanyl and bupivacaine also resulted in a sufficient level of analgesia.

Conclusions and Clinical Relevance—Use of the 3 anesthetic techniques permitted ovariohysterectomy with sufficient analgesia and acceptable neuroendocrine modulation of pain with minimal adverse effects.

Abstract

Objective—To compare cardiovascular and systemic effects and analgesia during the postoperative period of epidural anesthesia performed with bupivacaine alone or with fentanyl or sufentanil in bitches maintained at a light plane of anesthesia with continuous infusion of propofol.

Study Design—Prospective randomized masked clinical trial.

Animals—30 female dogs of various breeds.

Procedures—Dogs were allocated into 3 groups of 10 each. One group received fentanyl (2 μg/kg [0.91 μg/lb]) and bupivacaine (1 mg/kg [0.45 mg/lb]), 1 group received sufentanil (1 μg/kg) and bupivacaine (1 mg/kg), and 1 group received bupivacaine (1 mg/kg). All dogs received acepromazine (0.1 mg/kg [0.045 mg/lb]) and continuous infusion of propofol for sedation. The agents were administered into the lumbosacral space and diluted in saline (0.9% NaCl) solution to a total volume of 0.36 mL/kg (0.164 mL/lb). Cardiac and respiratory rates, arterial blood pressures, pH, and blood gases were evaluated. Analgesia, sedation level, serum cortisol concentrations, and plasma catecholamine concentrations were measured regularly for 6 hours.

Results—No important changes in cardiovascular, respiratory, or sedation variables were observed. Degree of analgesia in the postoperative period was higher in the sufentanil group, although use of fentanyl and bupivacaine also resulted in a sufficient level of analgesia.

Conclusions and Clinical Relevance—Use of the 3 anesthetic techniques permitted ovariohysterectomy with sufficient analgesia and acceptable neuroendocrine modulation of pain with minimal adverse effects.

Epidural anesthesia is considered an extremely safe procedure. When it is adequately performed, it can be used efficiently for a wide variety of surgical procedures. Although epidural anesthesia is widely used in veterinary medicine, it is usually performed with local anesthetics and a vasoconstrictor, and when additional analgesia is required, morphine is the agent of choice. The use of opioids in the epidural space in humans can be associated with many adverse effects such as respiratory depression, excessive sedation, vomiting, urinary retention, and pruritis.1 Nevertheless, because the combination of local anesthetics and opioids results in a synergistic effect, the dose and the dose-dependent effects of the agents can be reduced.2,3 Advantages of regional anesthetic techniques, compared with general anesthesia, include lower mortality and morbidity rates,4 no need for orotracheal intubation,5 better postoperative analgesia, and a decrease in surgical stress through the blockade of afferent nociceptive pathways and efferent sympathetic impulses to the pancreas and adrenal medulla.

Benefits of sufentanil in relation to morphine include rapid effect and higher analgesic potency because of its high liposolubility, intermediate degree of ionization, low molecular weight, high affinity for μreceptors, and wide therapeutic margin.6 In humans, sufentanil reaches maximum plasma concentration 20 minutes after epidural administration, with minimal motor blockade.7 A good margin of safety is also observed in dogs when sufentanil is administered IV.8 Cohen et al9 determined that the necessary dose for sufentanil to induce analgesia is the same for epidural or IV administration.

Fentanyl is a pure M-opioid agonist. As an analgesic, it is estimated to be 100 times as potent as morphine when administered IV but only 4 times as potent when administered intrathecally.10 The potency ratio of sufentanil versus fentanyl when administered into the epidural space is 5:1.11 Epidurally administered morphine at a dose of 0.1 mg/kg (0.045 mg/lb) has an onset time of 20 to 60 minutes and duration of action of 16 to 24 hours.12 Equipotent epidurally administered doses of sufentanil and fentanyl in women undergoing labor have an onset time of 20 minutes and a duration of action of 2 to 3 hours.13

The low doses of sufentanil and fentanyl presently used in humans do not completely eliminate the possibility of respiratory depression. However, fentanyl and sufentanil are opioids that are highly liposoluble and migrate less than morphine in the intrathecal space. For this reason, late respiratory depression is less commonly observed after epidural administration.6

To our knowledge, the cardiovascular and analgesic effects of sufentanil and fentanyl have not been evaluated when administered by the epidural route in bitches undergoing ovariohysterectomy. Therefore, the purpose of the study reported here was to compare cardiovascular and systemic effects and analgesia during the postoperative period of epidural anesthesia performed with bupivacaine alone or with fentanyl or sufentanil in bitches maintained at a light plane of anesthesia with continuous infusion of propofol.

Materials and Methods

Animals—Thirty female dogs of different breeds and ages, admitted to the Surgery Department for ovariohysterectomy, were used in this study. History and physical examination were used to determine whether the dogs met the inclusion criteria of minimum weight of 6 kg (13.2 lb), systolic arterial pressure > 120 mm Hg as measured by use of the oscillometric method, normal results of neurologic examination, normal skin over the epidural injection site, and absence of known systemic diseases. The study was approved by the Bioethical Committee of the University of São Paulo, and owner's consent was obtained.

The dogs were randomly allocated into 3 groups of 10 each and were evaluated by the same observer who was unaware of group assignments. All dogs first received acepromazinea (0.1 mg/kg, IM) as preanesthetic medication. Fifteen minutes later, a catheter was inserted into the cephalic vein for subsequent administration of propofolb and lactated Ringer's solution at a rate of 10 mL/kg/h (4.5 mL/lb/h) during the surgical procedure. Clipping and surgical preparation were performed on the lumbar region before administration of the epidural agents. To facilitate the epidural injection, dogs received propofol (4 mg/kg [1.8 mg/lb], IV) to induce a light plane of anesthesia and were positioned in sternal recumbecy. A 19-gauge Tuohy needle was inserted into the lumbosacral space, and proper positioning was confirmed by lack of resistance to injection of saline (0.9% NaCl) solution and subsequent ease of introduction of a 20-gauge epidural catheterc up to the L5-6 intervertebral space. The position of the catheter was verified radiographically at the end of the surgery by injection of 0.8 mL of iohexol.d Dogs in a group termed the fentanyl-bupivacaine group received fentanyle (2 μg/kg [0.91 μg/lb]) and 0.5% bupivacainef (1 mg/kg [0.45 mg/lb]), dogs in a group termed the sufentanil-bupivacaine group received sufentanilg (1 μg/kg) and 0.5% bupivacaine (1 mg/kg), and dogs in a group termed the bupivacaine group received 0.5% bupivacaine (1 mg/kg). For all groups, the drugs were diluted in saline solution in a volume equivalent to 0.36 mL/kg (0.164 mL/lb) and were administered during 1 minute; dogs were maintained in sternal recumbency for at least 15 minutes to facilitate the uniform spread of the drugs. Immediately before the beginning of the surgical procedure, a second dose of propofol (4 mg/kg, IV) was administered, followed by a continuous infusion of the same agent (0.2 mg/kg/min [0.09 mg/lb/min]) that was adjusted as necessary to maintain a light plane of anesthesia and the presence of reflexes. After propofol administration, dogs were positioned in dorsal recumbency. Cardiac and respiratory frequencies; systolic, diastolic, and mean arterial blood pressures measured by use of an oscillometric method with the appropriate-sized cuff placed at the metacarpus; and peripheral SaO2 with the probe positioned in the vulva were evaluated by means of a multivariable analyzerh at 3 times: time 0, before administration of propofol and the epidurally administered drugs; 30 minutes after epidural injection and at the beginning of the continuous infusion of propofol; and 60 minutes after epidural injection. All ovariohysterectomies were performed by the same surgeon by use of the 3-hemostats technique, beginning 30 minutes after the epidural injection. During surgery, the degree of abdominal relaxation (mild, moderate, or intense) was evaluated by the surgeon.

To evaluate the latency of motor blockade, pressure on an interdigital space of a hind foot was made with hemostats protected with rubber immediately after the epidural anesthesia and every 2 minutes until complete motor blockade was reached, which was detected when the dog could not retract its limb. To evaluate the onset time of sensory blockade, the same procedure was used. To differentiate the motor blockade from the sensory blockade, absence of painful sensation was verified by the absence of groaning, biting attempts, looking at the limb, and head shaking after the painful stimulus was performed with the hemostats. The spread of the blockade was evaluated via dermatomes by use of the panniculi test (pinching between the spinous process in the region of the vertebral column). To evaluate the duration of effect of the drugs, the same methodology used for evaluation of latency was used. This evaluation was performed every 15 minutes after completion of the surgical procedure.

Postoperative evaluation—Analgesia, sedation, heart rate, respiratory rate, and arterial blood pressure were measured postoperatively at 90, 120, 180, 240, 300, and 360 minutes after epidural injection. The degrees of analgesia and sedation were evaluated by use of the VAS, in which 0 corresponds to no pain or no sedation and 10 corresponds to dogs with the worst pain possible, and the scale proposed by the Colorado State University Veterinary Teaching Hospital,14 in which 0 corresponds to no pain and 25 to the worst pain possible. Rescue analgesia with morphinei (0.1 mg/kg, IM) was planned for dogs with pain scores of 4 or higher for VAS or 10 or higher for the Colorado scale. Administration of morphine was to be repeated every 10 minutes until the score was lowered to an acceptable value. After the end of the study period, dogs received tramadolj (2 mg/kg, PO) every 8 hours for 3 days and a single dose of carprofenk (4.4 mg/kg [2 mg/lb], SC), followed by oral administration of an equal dose for 3 days.

pH and blood gases—Blood samples were collected at 0, 60, 120, and 360 minutes after the epidural injection via puncture of the femoral artery with a heparinized plastic syringe attached to a 25 × 8-mm needle covered with a rubber cap. Immediately after each collection, the samples were analyzed in a pH and blood gas analyzerl for pH, PaO2, PaCO2 and SaO2.

Serum cortisol and plasma catecholamine measurements—Samples for serum cortisol and plasma catecholamine analyses were collected at 0, 60, 120, and 360 minutes after epidural injection. To determine plasma catecholamine concentrations, jugular vein blood samples were collected in plastic syringes and transferred to glass tubes containing 100 μL of anticoagulant (glutathione plus EDTA). Samples were immediately centrifuged in a freezing centrifugem for 10 minutes at 2,500 × g at 4°C. Blood samples were then transferred to 1.5-mL glass tubes and frozen at −80°C for later processing. Measurements of epinephrine and norepinephrine were performed via high-performance liquid chromatographyn at the Clinical Laboratory of the Heart Institute of the University of São Paulo.

To determine serum cortisol concentration, jugular vein blood samples were collected through plastic syringes, transferred to glass tubes, and centrifuged at 1,500 × g for 10 minutes. Serum samples were frozen at −20°C for later processing by means of a fluoroimmunoassay.o Measurements were made in duplicate in the Hormones Laboratory of the Clinics Hospital, School of Medicine, University of São Paulo.

Statistical analysis—To verify differences among groups, ANOVA was used with the assumption of gamma distribution15 of the observations of latency and duration of sensory and motor blockades. For catecholamines, ANOVA for repeated measures was used with the assumption of marginal gamma distribution.16 For the other measurements, ANOVA for repeated measures followed by the Bonferroni test17 for multiple comparisons was used to evaluate differences among time points within the same group and among groups. For all measurements, mean and SD values were determined. For all comparisons, P < 0.05 was considered significant.

Results

No significant differences were observed in age or weight of the dogs among the 3 groups. For latency of the motor blockade, the sufentanil-bupivacaine group had a significantly shorter time (4.2 ± 1.03 minutes), compared with the fentanyl-bupivacaine group (10.3 ± 10.53 minutes) and bupivacaine group (9.9 ± 10.79 minutes). For latency of the sensory blockade (28.5 ± 4.7 minutes, 21.3 ± 6.5 minutes, and 25.9 ± 3.7 minutes for the fentanyl-bupivacaine, sufentanil-bupivacaine, and bupivacaine groups, respectively), duration of the sensory blockade (206.1 ± 50.2 minutes, 239 ± 60.4 minutes, 205 ± 78.2 minutes for the fentanylbupivacaine, sufentanil-bupivacaine, and bupivacaine groups, respectively), duration of the motor blockade (200.6 ± 89.7 minutes, 251.5 ± 75.2 minutes, 229 ± 75.7 minutes for the fentanyl-bupivacaine, sufentanilbupivacaine, and bupivacaine groups, respectively), and anatomic extent of the blockade among the groups, there were no significant differences. For the fentanylbupivacaine group, the blockade reached from T10 to L2, for the sufentanil-bupivacaine group from T10 to L1, and for the bupivacaine group from T10 to L1.

All groups had similar changes in heart rate, respiratory rate, systolic and mean arterial pressures, arterial blood gas values, acid-base values, and SaO2 (Tables 1–4). In the fentanyl-bupivacaine and bupivacaine groups, heart rates at 30, 60, and 90 minutes after epidural injection were significantly lower than control values (time 0), whereas in the sufentanil-bupivacaine group, the decrease in heart rate was significant only at 60 and 90 minutes after the epidural injection. Respiratory rate was decreased significantly at 30 to 360 minutes after epidural injection in all groups. Diastolic blood pressure was significantly lower in the sufentanilbupivacaine group than the other groups at time 0 and at 240 to 360 minutes after epidural injection. In the fentanyl-bupivacaine and bupivacaine groups, all arterial blood pressures were significantly lower at 30 to 90 minutes, compared with values at time 0. In the sufentanil-bupivacaine group, systolic arterial pressure was similar to that of the other 2 groups; however, mean arterial pressure and diastolic arterial pressure were decreased significantly only at 30 minutes, compared with values at time 0. The pH was decreased significantly at 60 minutes, whereas PaCO2 was increased significantly at 60 minutes and decreased at 360 minutes. A high degree of abdominal relaxation was reported in all groups by the surgeon. Recovery after anesthesia was without complications for all dogs. There were no differences in the dose of propofol needed for each group (0.27 ± 0.05 mg/kg/min [0.123 ± 0.023 mg/lb/min], 0.29 ± 0.06 mg/kg/min [0.13 ± 0.027 mg/lb/min], and 0.28 ± 0.08 mg/kg/min [0.132 ± 0.027 mg/lb/min] for the fentanyl-bupivacaine, sufentanil-bupivacaine, and bupivacaine groups, respectively). Duration of surgery was 41 ± 14.5 minutes, 39.0 ± 14.2 minutes, 37.0 ± 8.7 minutes for the fentanyl-bupivacaine, sufentanil-bupivacaine, and bupivacaine groups, respectively.

Table 1—

Mean ± SD heart rate (HR [beats/min]) and respiratory rate (RR [breaths/min]) in dogs (n = 10/group) that received an epidural injection of fentanyl-bupivacaine, sufentanil-bupivacaine, or bupivacaine in association with propofol.

Time (min)Fentanyl-bupivacaine groupSufentanil-bupivacaine groupBupivacaine group
HRRRHRRRHRRR
0124 ± 2542 ± 18117 ± 2034 ± 13124 ± 1335 ± 11
30101 ± 20*20 ± 4*119 ± 3624 ± 10*97 ± 12*22 ± 8*
60103 ± 19*22 ± 6*112 ± 35*22 ± 7*102 ± 20*24 ± 7*
9093 ± 13*22 ± 6*104 ± 32*21 ± 5*102 ± 19*22 ± 3*
120124 ± 2724 ± 6*118 ± 2319 ± 6*127 ± 3524 ± 6*
180121 ± 2720 ± 5*122 ± 2423 ± 4*133 ± 2727 ± 6*
240117 ± 2422 ± 5*118 ± 2225 ± 2*124 ± 2427 ± 7*
300113 ± 2721 ± 3*122 ± 2024 ± 5*120 ± 2427 ± 7*
360110 ± 1922 ± 4*108 ± 1122 ± 6*125 ± 1926 ± 6*

Significantly (P < l0.05) different from value at time 0.

Table 2—

Mean ± SD systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressures (mm Hg) in the same dogs as in Table 1.

Time (min)Fentanyl-bupivacaine groupSufentanil-bupivacaine groupBupivacaine group
SAPMAPDAPSAPMAPDAPSAPMAPDAP
0151 ± 19110 ± 1683 ± 16139 ± 1992 ± 1466 ± 8*145 ± 14103 ± 1777 ± 18
30115 ± 1875 ± 1053 ± 15110 ± 2376 ± 1957 ± 19108 ± 2166 ± 1649 ± 12
60128 ± 2388 ± 1966 ± 26127 ± 3097 ± 2876 ± 23119 ± 2685 ± 2368 ± 20
90135 ± 2595 ± 2071 ± 16124 ± 2192 ± 2370 ± 19124 ± 1686 ± 2272 ± 21
120137 ± 18103 ± 2081 ± 25128 ± 1497 ± 1676 ± 17124 ± 1998 ± 1981 ± 20
180143 ± 13117 ± 997 ± 15134 ± 27106 ± 2386 ± 18127 ± 2492 ± 2374 ± 21
240131 ± 1699 ± 1377 ± 19121 ± 3191 ± 3073 ± 29*137 ± 20103 ± 2285 ± 22
300137 ± 19108 ± 1984 ± 16121 ± 1888 ± 2072 ± 19*136 ± 12103 ± 2283 ± 21
360133 ± 19107 ± 2288 ± 25134 ± 23101 ± 2377 ± 22*150 ± 17116 ± 1691 ± 15

Significantly (P < l0.05) different from values in other groups.

Significantly (P < l0.05) different from value at time point 0.

Table 3—

Mean ± SD blood gas variables in the same dogs as in Table 1.

VariableGroupTime
0 min60 min120 min360 min
Sao2Fentanyl97.06 ± 1.0695.62 ± 2.8397.30 ± 1.296.8 ± 1.15
Sufentanil95.84 ± 1.5695.40 ± 2.7696.53 ± 2.496.75 ± 0.86
Bupivacaine97.02 ± 0.9495 ± 3.397.1 ± 1.696.6 ± 0.97
Paco2Fentanyl32.11 ± 3.8341.4 ± 11.93*35.8 ± 7.2730.63 ± 3.81
Sufentanil32.2 ± 5.4339.11 ± 4.81*36 ± 4.0930.55 ± 3.18
Bupivacaine31.18 ± 2.8435.38 ± 5.76*32.9 ± 3.5429.4 ± 2.46
pHFentanyl7.36 ± 0.067.26 ± 0.08*7.34 ± 0.077.39 ± 0.03
Sufentanil7.37 ± 0.047.28 ± 0.03*7.34 ± 0.037.39 ± 0.02
Bupivacaine7.37 ± 0.037.29 ± 0.06*7.35 ± 0.037.39 ± 0.02
HCO3Fentanyl17.29 ± 1.7419.37 ± 2.4118.6 ± 1.2418.28 ± 1.97
Sufentanil17.72 ± 2.5417.95 ± 2.7319.1 ± 1.9717.99 ± 1.63
Bupivacaine17.35 ± 1.8318.73 ± 2.4518 ± 1.7617.30 ± 1.70

Significantly (P < 0.05) different from values at times 0, 120, and 360 minutes.

Significantly (P < 0.05) different from value at 120 minutes.

Table 4—

Mean ± SD peripheral Sao2 (%) in the same dogs as in Table 1.

GroupTime
30 min60 min90 min
Fentanyl94.5 ± 2.0195.1 ± 3.6395.5 ± 2.59
Sufentanil93.9 ± 2.6095 ± 2.6795 ± 2.87
Bupivacaine95.2 ± 2.7495.3 ± 2.9595.6 ± 2.32

Plasma norepinephrine concentrations decreased significantly in all groups after epidural administration (Figure 1) and did not change for cortisol (time 0: 2.18 ± 1.44, 1.72 ± 1.07, and 1.34 ± 0.97; 60 minutes: 2.85 ± 1.38, 2.05 ± 1.5, and 2.77 ± 0.95; 120 minutes: 1.75 ± 1.62, 2.05 ± 1.72, and 2.35 ± 1.55; and 360 minutes: 1.99 ± 0.75, 1.87 ± 1.5, and 2.06 ± 0.97 for the fentanyl-bupivacaine, sufentanilbupivacaine, and bupivacaine groups, respectively).

Figure 1—
Figure 1—

Mean ± SD plasma norepinephrine concentrations in dogs (n = 10/group) that received an epidural injection of fentanylbupivacaine (FB), sufentanil-bupivacaine (SB), or bupivacaine (B) in association with propofol. *Significantly (P < 0.05) different from value at time 0. †Significantly (P < 0.05) different from value at 60 minutes.

Citation: Journal of the American Veterinary Medical Association 230, 1; 10.2460/javma.230.1.45

During the postoperative observation period in all groups, the VAS values did not vary significantly with time. However, the sufentanil-bupivacaine group had lower values, which were significantly different in relation to the bupivacaine group 360 minutes after epidural injection (Figure 2). For sedation values, according to the same criteria (VAS values), a decrease in all groups was observed with time. For analgesia and sedation values, according to the Colorado scale, a decrease in all groups was observed during the postoperative period and the sufentanil-bupivacaine group had significantly lower values than those observed in the bupivacaine group 360 minutes after the epidural injection (Figure 3). In the bupivacaine group, scores of analgesia were significantly lower at 180 to 360 minutes after epidural injection than control values (time 0). No dogs in any group needed analgesic rescue medication during the postoperative period.

Figure 2—
Figure 2—

Mean ± SD scores for pain assessment (VAS) in the same dogs as in Figure 1. *Values in the B group significantly (P < 0.05) different from values in the SB group. See Figure 1 for key.

Citation: Journal of the American Veterinary Medical Association 230, 1; 10.2460/javma.230.1.45

Figure 3—
Figure 3—

Mean ± SD scores for postoperative pain and sedation assessment (Colorado State University Veterinary Teaching Hospital scale) in the same dogs as in Figure 1. *Significant (P < 0.05) differences among all time points. †Significant (P < 0.05) difference between the B and SB groups. See Figure 1 for key.

Citation: Journal of the American Veterinary Medical Association 230, 1; 10.2460/javma.230.1.45

Discussion

The use of opioid analgesics, especially sufentanil, slightly enhanced the analgesia obtained through administration of bupivacaine. Use of bupivacaine alone in equal doses but with higher volume and dilution than that recommended in the literature (0.22 mL/kg [0.1 mL/lb])6,18 appeared quite adequate for the epidural anesthetic procedure.

Massone18 reported that epidural anesthesia, performed with local anesthetics and the volume commonly used, applied at the lumbosacral epidural space in bitches was not adequate for ovariohysterectomy because it does not result in desensitization of the ligamentum ovarii proprium. According to results obtained by Rocha,p innervation of the ligamentum ovarii proprium depends on the afferent fibers from the first lumbar vertebra, which requires high volumes of anesthetic for desensitization. Nevertheless, in the present study, the concentration and dose of the applied drugs and the anatomic extent of the resultant nerve block made the surgical procedure possible by use of propofol in a dose sufficient only to induce a light plane of anesthesia.

Because of the dose and concentration of the drugs used in the present study, all dogs had adequate motor blockade. The shorter latency time of motor blockade observed in the sufentanil-bupivacaine group was attributable to sufentanil having rapid effect and high analgesic potency because of its high liposolubility, intermediate grade of ionization, and low molecular weight8; this results in quick passage through the dura mater, which is clinically reflected in a short latency period.19 It must be noted that the dose of sufentanil used here was 2.5 times the equipotent dose of fentanyl, which may have contributed to the observed results. Other authors20 used different ratios, and the choice of this dose was based on our experience in pilot studies.

Latency of the sensory blockade in the present study was similar in all groups. Similar results were described by Braz et al.21 However, Johnson et al,22 who compared use of bupivacaine alone with use of bupivacaine and fentanyl in the epidural space of patients undergoing cesarean section, determined that use of the combined drugs reduced the time of latency of the sensory blockade by 35%.

Hypotension is an undesirable effect of epidural anesthesia and is caused by rostral spread of the local anesthetic with subsequent sympathetic blockade.23 The degree of sympathetic blockade depends on the site of injection, dose of local anesthetic, and the preexisting state of the circulation.24

In veterinary medicine, because the blockade is performed in the lumbosacral space of the animal, the occurrence of high sympathetic blockade is rare and transitory. In the present study, despite the fact that the blockade probably extended to the thoracic vertebrae, hypotension was not observed in any group. The dose of bupivacaine used and the technique applied (use of an epidural catheter and the slow velocity of injection) might have contributed to less sympathetic blockade. The sufentanil group had lower values of diastolic blood pressure, but values were within the reference range for dogs. Those data were in agreement with data reported by Futema,q who used a combination of sufentanil and bupivacaine in bitches and did not detect hemodynamic alterations.

During surgery, values of pH decreased, whereas bicarbonate and PaCO2 increased in all 3 groups, suggesting mild respiratory depression. This may have been associated with infusion of propofol because when infusion was discontinued, those values returned to baseline. Weaver and Raptopoulos,25 during anesthesia with propofol, observed a reduction in ventilation and an increase in PaCO2 and suggested use of supplemental oxygen. Aguiar et al26 observed dose-dependent respiratory depression represented by a decrease in respiratory rate, an increase in end-tidal CO2 and PaCO2, and a decrease in PaO2 when they used a continuous infusion of propofol in dogs. Those observations also explain what occurred in the study reported here.

Comparison of the analgesic potency of these protocols was one of the aims of this study. For this reason, objective evaluations such as cortisol and catecholamine measurements as well as subjective evaluations such as the VAS scale and the descriptive scale were used. These methods have been well documented in human27,28 and veterinary literature.14,29,30 Dogs were evaluated by the same observer who was unaware of group assignments, which permitted unbiased evaluation of the analgesic effects of the drugs.31 To make comparisons possible and to validate the methods of the evaluation chosen here, the control group received only bupivacaine.

Dogs in the sufentanil-bupivacaine group had significantly lower scores of pain according to the VAS, compared with dogs in the bupivacaine group. Still, all dogs in the present study had low pain scores, and rescue medication was not needed. These results were similar to those observed by Rolfseng et al32 and Capogna et al,33 who compared the analgesic potency of fentanyl and sufentanil combined with bupivacaine in women during parturition. The high liposolubility of sufentanil probably promotes rapid transfer through the blood-brain barrier, which increases its potency when administered parentally. When this agent is administered into the epidural space, close to the action site, its high liposolubility promotes high reabsorption, causing a decrease in its potency in relation to fentanyl when administered into the epidural space.33

Opioids can cause sedation in the postoperative period and mask signs associated with pain and stress.19 For this reason, a sedation score was used in this study, which revealed that the high values obtained were mostly related to anesthetic recovery.

Single testing methods can result in erroneous findings. Thus, a combination of objective and subjective methods of evaluation is necessary for a more comprehensive and accurate analysis.34 As objective indicators, cortisol and catecholamine concentrations were also measured, and they did not differ among the studied groups and were similar to the results obtained with regard to pain.

Epidural anesthesia, when applied skillfully, is a simple and safe procedure and, depending on the agents, doses, and volumes used, is adequate for various surgical procedures. In the present study, because a volume higher than that described in the literature was used,18 the blockade reached the first lumbar vertebra and the afferent fibers of the aortic plexus,p which supplies the ovaries, oviducts, and uterus; this permitted ovariohysterectomy to be successfully performed. Additional studies are necessary to evaluate the applicability of the techniques used here and the use of lower doses, especially of bupivacaine, which could decrease the duration of motor blockade.

ABBREVIATIONS

VAS

Visual analogue scale

Sao2

Arterial oxyhemoglobin saturation

a.

Acepran, Univet, São Paulo, Brazil.

b.

Diprivan, AstraZeneca International, London, UK.

c.

20-gauge epidural catheter, BD, São Paulo, Brazil.

d.

Ominipaque, Sanofi-Synthelabo, Shanghai, China.

e.

Fentanil, Jansen Farmacêutica, São Paulo, Brazil.

f.

Neocaína, Cristália, São Paulo, Brazil.

g.

Fastffen, Cristália, São Paulo, Brazil.

h.

Viridia 685, Hamlett Packard, Boeblingen, Germany.

i.

Dimorf, Cristália, São Paulo, Brazil.

j.

Dorless, Agener, São Paulo, Brazil.

k.

Carproflan, Agener, São Paulo, Brazil.

l.

Gasometer, ABL 330, Radiometer, Copenhagen, Denmark.

m.

Model RT7, Sorvall, Fresno, Calif.

n.

Model 460, Waters, São Paulo, Brazil.

o.

AutoDelfia, Perkin Elmer, São Paulo, Brazil.

p.

Rocha LMS. Estudo anatomo-anestesiológico do segmento lombar (L1 a L6) em cães. Dissertação (Mestrado em Anatomia dos Animais Domésticos e Silvestres), Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, Brazil.

q.

Futema F. Avaliação hemodinâmica do emprego da associação de sufentanil e bupivacaína no espaço epidural em cães. Tese (Doutorado em Cirurgia), Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, Brazil.

References

  • 1

    Wood GE, Goresky GV, Klassen KA, et al. Complications of continuous epidural infusions for post operative analgesia in children. Can J Anaesth 1994;41:613620.

    • Search Google Scholar
    • Export Citation
  • 2

    Ackerman B, Arwenstrom E, Post C. Local anesthetics potentiate spinal morphine antinociception. Anesth Analg 1988;67:943948.

  • 3

    Kaneko M, Saito Y, Kirihara Y, et al. Synergistic antinociceptive interaction after epidural coadministration of morphine and lidocaine in rats. Anesthesiology 1994;80:137150.

    • Search Google Scholar
    • Export Citation
  • 4

    Christopherson R, Beattie C, Frank SM, et al. Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Anesthesiology 1993;79:422434.

    • Search Google Scholar
    • Export Citation
  • 5

    Urban MK, Urquhart B. Evaluation of brachial plexus anesthesia for upper extremity surgery. Reg Anesth 1994;19:175182.

  • 6

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

  • 7

    Lejus C, Schwoerer D, Furic I, et al. Fentanyl versus sufentanil: plasma concentrations during continuous epidural postoperative infusion in children. Br J Anaesth 2000;85:615617.

    • Search Google Scholar
    • Export Citation
  • 8

    De Castro J, Van de Waters A, Wouters L, et al. Comparative study of cardiovascular, neurological and metabolic side effects of eight narcotics in dogs. Acta Anaesthesiol Belg 1979;30:9599.

    • Search Google Scholar
    • Export Citation
  • 9

    Cohen SE, Tan S, White PF. Sufentanil analgesia following cesarean section: epidural versus intravenous administration. Anesthesiology 1998;68:129134.

    • Search Google Scholar
    • Export Citation
  • 10

    Palmer CM, Cork RC, Hays R, et al. The dose response relation of intrathecal fentanyl for labor analgesia. Anesthesiology 1998;88:355361.

    • Search Google Scholar
    • Export Citation
  • 11

    Herman NL, Sheu KL, Van Decar TK, et al. Determination of the analgesic dose-response relationship for epidural fentanyl and sufentanil with bupivacaine 0.125% in laboring patients. J Clin Anesth 1998;10:670677.

    • Search Google Scholar
    • Export Citation
  • 12

    Bonath KH, Saleh AS. Long term pain treatment in the dog by peridural morphines, in Proceedings. 2nd Int Cong Vet Anesth 1985;710.

  • 13

    Connelly NR, Parker RK, Vallurupalli V, et al. Comparison of epidural fentanyl versus epidural sufentanil for analgesia in ambulatory patients in early labor. Anesth Analg 2000;91:374378.

    • Search Google Scholar
    • Export Citation
  • 14

    Hellyer PW, Gaynor JS. Acute postsurgical pain in dogs and cats. Compend Contin Educ Small Anim Pract 1998;20:140153.

  • 15

    Nelder JA, Wedderburn RWM. Generalized linear models. J R Stat Soc 1972;135:370384.

  • 16

    Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:1322.

  • 17

    Neter J, Kutner MH, Nachtsheim CJ, et al. Applied linear statistical models. 4th ed. Chicago: Richard D. Irwin, 1996;1408.

  • 18

    Massone F. Anestesiologia veterinária: farmacologia e técnicas. 3rd ed.Rio de Janeiro: Guanabara Koogan, 1999;225.

  • 19

    Gozzane JL. Opióides espinhais em obstetricia. In:Yamashita AM, Gozzane JL, eds.Anestesia em obstetricia. São Paulo, Brazil: Atheneu, 1997;3342.

    • Search Google Scholar
    • Export Citation
  • 20

    Taylor PM, Houlton JEF. Postoperative analgesia in the dog: a comparison of morphine, buprenorphine and pentazocine. J Small Anim Pract 1984;25:437451.

    • Search Google Scholar
    • Export Citation
  • 21

    Braz JRC, Vanni SMD, Menezes JA, et al. Associação de opióides lipofílicos a bupivacaína na anestesia peridural. Há vantagem no aumento da dose do opióide? Rev Bras Anestesiol 1998;48:455467.

    • Search Google Scholar
    • Export Citation
  • 22

    Johnson C, Oriol N, Feinstein D, et al. Onset of action between bupivacaine 0.5% and bupivacaine 0.5% plus fentanil 75 μg. J Clin Anesth 1989;1:440443.

    • Search Google Scholar
    • Export Citation
  • 23

    Klide AM, Soma LR. Epidural analgesia in the dog and cat. J Am Vet Med Assoc 1968;153:165173.

  • 24

    Scott NB, Absalom AR. The features of regional anaesthesia. In:Wildsmith JAW, Armitage EN, McClure JH, eds.Principles and practice of regional anaesthesia. 3rd ed.New York: Churchill Livingstone Inc, 2003;920.

    • Search Google Scholar
    • Export Citation
  • 25

    Weaver BMQ, Raptopoulos D. Induction of anaesthesia in dogs and cats with propofol. Vet Rec 1990;126:617620.

  • 26

    Aguiar AJ, Luna SPL, Oliva VNLS, et al. Continuous infusion of propofol in dogs premedicated with methotrimeprazine. Vet Anaesth Analg 2001;28: 220.

    • Search Google Scholar
    • Export Citation
  • 27

    Lloyd-Thomas AR. Pain management in pediatric patients. Br J Anaesth 1990;64:85104.

  • 28

    Hopkins D, Shipton EA, Portgieter D, et al. Comparison of tramadol and morphine via subcutaneous PCA following major orthopedic surgery. Can J Anaesth 1998;45:435442.

    • Search Google Scholar
    • Export Citation
  • 29

    Lascelles BD, Butterworth SJ, Waterman AE. Postoperative analgesic and sedative effects of carprofen and pethidine in dogs. Vet Rec 1994;134:187190.

    • Search Google Scholar
    • Export Citation
  • 30

    Lascelles BDX, Cripps PJ, Lones A, et al. Efficacy and kinetics of carprofen, administered preoperatively or postoperatively, for the prevention of pain in dogs undergoing ovariohysterectomy. Vet Surg 1998;27:568582.

    • Search Google Scholar
    • Export Citation
  • 31

    Hansen B, Hardie E. Prescription and use of analgesics in dogs and cats in a veterinary teaching hosptial: 258 cases (1983– 1989). J Am Vet Med Assoc 1993;202:14851494.

    • Search Google Scholar
    • Export Citation
  • 32

    Rolfseng OK, Skogvoll E, Borchgrevink PC. Epidural bupivacaine with sufentanil or fentanyl during labour: a randomized, double-blind study. Eur J Anaesthesiol 2002;19:812818.

    • Search Google Scholar
    • Export Citation
  • 33

    Capogna G, Camorcia M, Colum M. Minimum analgesic doses of fentanyl and sufentanil for epidural analgesia in the first stage of labor. Anesth Analg 2003;96:4:11781182.

    • Search Google Scholar
    • Export Citation
  • 34

    Smith JD, Allen SW, Quandt JE. Changes in cortisol concentration in response to stress and postoperative pain in clientowned cats and correlation with objective clinical variables. Am J Vet Res 1999;60:432436.

    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Mean ± SD plasma norepinephrine concentrations in dogs (n = 10/group) that received an epidural injection of fentanylbupivacaine (FB), sufentanil-bupivacaine (SB), or bupivacaine (B) in association with propofol. *Significantly (P < 0.05) different from value at time 0. †Significantly (P < 0.05) different from value at 60 minutes.

  • Figure 2—

    Mean ± SD scores for pain assessment (VAS) in the same dogs as in Figure 1. *Values in the B group significantly (P < 0.05) different from values in the SB group. See Figure 1 for key.

  • Figure 3—

    Mean ± SD scores for postoperative pain and sedation assessment (Colorado State University Veterinary Teaching Hospital scale) in the same dogs as in Figure 1. *Significant (P < 0.05) differences among all time points. †Significant (P < 0.05) difference between the B and SB groups. See Figure 1 for key.

  • 1

    Wood GE, Goresky GV, Klassen KA, et al. Complications of continuous epidural infusions for post operative analgesia in children. Can J Anaesth 1994;41:613620.

    • Search Google Scholar
    • Export Citation
  • 2

    Ackerman B, Arwenstrom E, Post C. Local anesthetics potentiate spinal morphine antinociception. Anesth Analg 1988;67:943948.

  • 3

    Kaneko M, Saito Y, Kirihara Y, et al. Synergistic antinociceptive interaction after epidural coadministration of morphine and lidocaine in rats. Anesthesiology 1994;80:137150.

    • Search Google Scholar
    • Export Citation
  • 4

    Christopherson R, Beattie C, Frank SM, et al. Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Anesthesiology 1993;79:422434.

    • Search Google Scholar
    • Export Citation
  • 5

    Urban MK, Urquhart B. Evaluation of brachial plexus anesthesia for upper extremity surgery. Reg Anesth 1994;19:175182.

  • 6

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

  • 7

    Lejus C, Schwoerer D, Furic I, et al. Fentanyl versus sufentanil: plasma concentrations during continuous epidural postoperative infusion in children. Br J Anaesth 2000;85:615617.

    • Search Google Scholar
    • Export Citation
  • 8

    De Castro J, Van de Waters A, Wouters L, et al. Comparative study of cardiovascular, neurological and metabolic side effects of eight narcotics in dogs. Acta Anaesthesiol Belg 1979;30:9599.

    • Search Google Scholar
    • Export Citation
  • 9

    Cohen SE, Tan S, White PF. Sufentanil analgesia following cesarean section: epidural versus intravenous administration. Anesthesiology 1998;68:129134.

    • Search Google Scholar
    • Export Citation
  • 10

    Palmer CM, Cork RC, Hays R, et al. The dose response relation of intrathecal fentanyl for labor analgesia. Anesthesiology 1998;88:355361.

    • Search Google Scholar
    • Export Citation
  • 11

    Herman NL, Sheu KL, Van Decar TK, et al. Determination of the analgesic dose-response relationship for epidural fentanyl and sufentanil with bupivacaine 0.125% in laboring patients. J Clin Anesth 1998;10:670677.

    • Search Google Scholar
    • Export Citation
  • 12

    Bonath KH, Saleh AS. Long term pain treatment in the dog by peridural morphines, in Proceedings. 2nd Int Cong Vet Anesth 1985;710.

  • 13

    Connelly NR, Parker RK, Vallurupalli V, et al. Comparison of epidural fentanyl versus epidural sufentanil for analgesia in ambulatory patients in early labor. Anesth Analg 2000;91:374378.

    • Search Google Scholar
    • Export Citation
  • 14

    Hellyer PW, Gaynor JS. Acute postsurgical pain in dogs and cats. Compend Contin Educ Small Anim Pract 1998;20:140153.

  • 15

    Nelder JA, Wedderburn RWM. Generalized linear models. J R Stat Soc 1972;135:370384.

  • 16

    Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:1322.

  • 17

    Neter J, Kutner MH, Nachtsheim CJ, et al. Applied linear statistical models. 4th ed. Chicago: Richard D. Irwin, 1996;1408.

  • 18

    Massone F. Anestesiologia veterinária: farmacologia e técnicas. 3rd ed.Rio de Janeiro: Guanabara Koogan, 1999;225.

  • 19

    Gozzane JL. Opióides espinhais em obstetricia. In:Yamashita AM, Gozzane JL, eds.Anestesia em obstetricia. São Paulo, Brazil: Atheneu, 1997;3342.

    • Search Google Scholar
    • Export Citation
  • 20

    Taylor PM, Houlton JEF. Postoperative analgesia in the dog: a comparison of morphine, buprenorphine and pentazocine. J Small Anim Pract 1984;25:437451.

    • Search Google Scholar
    • Export Citation
  • 21

    Braz JRC, Vanni SMD, Menezes JA, et al. Associação de opióides lipofílicos a bupivacaína na anestesia peridural. Há vantagem no aumento da dose do opióide? Rev Bras Anestesiol 1998;48:455467.

    • Search Google Scholar
    • Export Citation
  • 22

    Johnson C, Oriol N, Feinstein D, et al. Onset of action between bupivacaine 0.5% and bupivacaine 0.5% plus fentanil 75 μg. J Clin Anesth 1989;1:440443.

    • Search Google Scholar
    • Export Citation
  • 23

    Klide AM, Soma LR. Epidural analgesia in the dog and cat. J Am Vet Med Assoc 1968;153:165173.

  • 24

    Scott NB, Absalom AR. The features of regional anaesthesia. In:Wildsmith JAW, Armitage EN, McClure JH, eds.Principles and practice of regional anaesthesia. 3rd ed.New York: Churchill Livingstone Inc, 2003;920.

    • Search Google Scholar
    • Export Citation
  • 25

    Weaver BMQ, Raptopoulos D. Induction of anaesthesia in dogs and cats with propofol. Vet Rec 1990;126:617620.

  • 26

    Aguiar AJ, Luna SPL, Oliva VNLS, et al. Continuous infusion of propofol in dogs premedicated with methotrimeprazine. Vet Anaesth Analg 2001;28: 220.

    • Search Google Scholar
    • Export Citation
  • 27

    Lloyd-Thomas AR. Pain management in pediatric patients. Br J Anaesth 1990;64:85104.

  • 28

    Hopkins D, Shipton EA, Portgieter D, et al. Comparison of tramadol and morphine via subcutaneous PCA following major orthopedic surgery. Can J Anaesth 1998;45:435442.

    • Search Google Scholar
    • Export Citation
  • 29

    Lascelles BD, Butterworth SJ, Waterman AE. Postoperative analgesic and sedative effects of carprofen and pethidine in dogs. Vet Rec 1994;134:187190.

    • Search Google Scholar
    • Export Citation
  • 30

    Lascelles BDX, Cripps PJ, Lones A, et al. Efficacy and kinetics of carprofen, administered preoperatively or postoperatively, for the prevention of pain in dogs undergoing ovariohysterectomy. Vet Surg 1998;27:568582.

    • Search Google Scholar
    • Export Citation
  • 31

    Hansen B, Hardie E. Prescription and use of analgesics in dogs and cats in a veterinary teaching hosptial: 258 cases (1983– 1989). J Am Vet Med Assoc 1993;202:14851494.

    • Search Google Scholar
    • Export Citation
  • 32

    Rolfseng OK, Skogvoll E, Borchgrevink PC. Epidural bupivacaine with sufentanil or fentanyl during labour: a randomized, double-blind study. Eur J Anaesthesiol 2002;19:812818.

    • Search Google Scholar
    • Export Citation
  • 33

    Capogna G, Camorcia M, Colum M. Minimum analgesic doses of fentanyl and sufentanil for epidural analgesia in the first stage of labor. Anesth Analg 2003;96:4:11781182.

    • Search Google Scholar
    • Export Citation
  • 34

    Smith JD, Allen SW, Quandt JE. Changes in cortisol concentration in response to stress and postoperative pain in clientowned cats and correlation with objective clinical variables. Am J Vet Res 1999;60:432436.

    • Search Google Scholar
    • Export Citation

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