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Analgesic, hemodynamic and respiratory effects of caudal epidurally administered ropivacaine hydrochloride in mares
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
Analgesic, hemodynamic and respiratory effects of caudal epidurally administered ropivacaine hydrochloride in mares Roman T Skarda
Dr. med. vet., PhD, Dip ACVA, Dip ECVA;
William W Muir
DVM, PhD, Dip ACVA, Dip ACVECC
Department of Veterinary Clinical Sciences,The Ohio State University,601 Vernon L. Tharp Street, Columbus, Ohio 43210^1089, USA
Correspondence: R. T. Skarda, Department of Veterinary Clinical Sciences,The Ohio State University, 601 Vernon L. Tharp Street, Columbus, Ohio 43210^1089, USA
Abstract Objective To determine the analgesic, hemodynamic and respiratory e¡ects, sedation and ataxia in mares of caudal epidural administration of ropivacaine hydrochloride solution. Study design Prospective, single-dose trial. Animals Ten healthy mares weighing from 475 to 565 kg. Methods Intravascular catheters and an epidural needle were placed after in¢ltration of the skin and subcutaneous tissues with 2% lidocaine. Ropivacaine (0.5%, 8 or 9 mL) was then injected epidurally at the ¢fth sacral or sacrococcygeal vertebrae, respectively. Analgesia was determined by lack of sensory perception to electrical stimulation (> 40 milliamps) and absence of response to needle pricks extending from coccyx to S2 dermatomes. Electrocardiogram, heart and respiratory rates, rectal temperature, arterial blood pressure, arterial acid-base (pH, standard bicarbonate and base excess), gas tensions (PO2, PCO2), PCV, oxyhemoglobin and total solids concentrations, and numerical scores of perineal analgesia, sedation (head drop), and ataxia (position of pelvic limbs) were determined before and during a 5-hour testing period. Analysis of variance (ANOVA) with repeated measures was used to detect signi¢cant (p < 0.05) di¡erences of mean values from baseline.
Results Epidurally administered ropivacaine induced variable analgesia extending bilaterally from coccyx to S2 (three mares), coccyx to S3 (four mares), and coccyx to S4 (three mares), with minimal sedation, ataxia, and cardiovascular and respiratory disturbances of mares. Perineal analgesia was attained at 10 4 minutes and lasted for 196 42 minutes (mean SD). Five mares demonstrated inadequate perineal analgesia, probably attributable to deviation of the spinal needle from the midline. They were successfully blocked with ropivacaine on another occasion. Epidural ropivacaine signi¢cantly reduced repiratory rates of mares and did not change other variables from baseline. Conclusions and clinical relevance Ropivacaine (0.5%, 8 mL 500 kg 1) can be administered caudal epidurally to produce prolonged (> 2.5 hours) bilateral perineal analgesia with minimal sedation, ataxia, and circulatory and respiratory disturbances in standing mares. Keywords caudal epidural, mares, ropivacaine.
Introduction The local anesthetics lidocaine and mepivacaine and the alpha2-adrenoceptor agonists xylazine and detomidine are routinely used for epidural administration in horses. These drugs are either too short 61
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
acting (lidocaine, mepivacaine;1^2 hours;) or produce ataxia and signi¢cant CNS and cardiovascular depression (xylazine, detomidine) in mares (Skarda & Muir 1983; 1996a; 1996b). They have the potential to produce postural instability, rear limb ataxia, recumbency and excitement in horses contributing to increased morbidity and mortality (Skarda1996). Death or cardiotoxicity in human obstetric patients, probably after unintentional intravascular administration of bupivacaine or etidocaine, prompted the search for drugs with less cardiotoxicity (Albright1979; Nancarrow et al.1989; Alahuhta et al. 1995; Knudsen et al.1997). Ropivacaine is the newest member of the amino-amide class of long-acting local anesthetics to be introduced and become commercially available in more than 25 years. It is structurally related to, but unlike bupivacaine and mepivacaine, which are supplied commercially as racemic mixtures of two stereo-isomers, ropivacaine is provided as the hydrochloride of the pure S-(^) enantiomer (DeJong 1995; Etches et al. 1997). Ropivacaine blocks the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation, and reducing the rate of rise of the action potential (Ðkerman et al. 1988; Wicks 1995). Epidurally and intravenously administered ropivacaine have been studied for surgical anesthesia (Kerkamp et al. 1990b; Schug et al. 1996; Klein et al. 1998; Hartmannsgruber et al. 1999), acute postoperative pain management (Scott et al. 1995, 1999; Schug et al. 1996; Brodner et al. 1999; Liu et al. 1999; Kampe et al. 1999), and obstetrical procedures in human beings (Brown et al. 1990; Alahuhta et al. 1995; Gri¤n & Reynolds1995;Tuttle et al.1995; Owen et al. 1998; Scrutton et al. 1998; Zwack et al. 1999; Brodner et al. 1999; Cohen et al. 1999; Gautier et al. 1999; Polley et al. 1999; Santos et al. 1999; Vallejo et al. 1999a, b). Clinical trials in volunteers and patients suggest that ropivacaine is similar to bupivacaine in onset, depth, duration and extent of sensory blockade, although motor block is less intense and of shorter duration (Kerkamp & Gielen 1990a; Brockway et al. 1991; Gri¤n & Reynolds 1995; Zaric et al. 1996; Etches et al. 1997; D'A ngelo & James 1999; Koinig et al.1999). An abstract about the onset, duration and ataxia of epidurally administered ropivacaine (1% solution) in six mares (320 24 kg) has recently been reported (Luna et al. 2000). We hypothesized that epidurally administered ropivacaine (0.5% solution) would provide profound and long-lasting (2^4 hours) perineal 62
analgesia with only minimal sedation and ataxia, changes in behavior or cardiovascular and respiratory depression in mares.
Materials and methods Mares The study protocol was approved by the Ohio State University Institutional Animal Care and Use Committee. Ten healthy mares (¢ve Thoroughbreds, ¢ve Standardbreds) from 10 to 20 years old weighing 475^565 kg (Table 1) were studied to assess analgesic, systemic hemodynamic and respiratory e¡ects, sedation and ataxia in mares after the epidural administration of ropivacaine hydrochloride solution. Mare preparation The left carotid artery had been surgically elevated to a subcutaneous position in all mares at least 10 weeks prior to the study. Other surgical procedures were not performed on the mares. All mares were considered healthy on the basis of the results of physical examination, WBC count, and ECG. The mares were allowed ad libitum access to food and water until the beginning of each experiment. All trials were performed between 0900 and 1700 hours in a quiet, climate-controlled room. Mares were standing in restraining stocks for the duration of the study. The hair over the area of the mares' left carotid artery, right jugular furrow and sacrococcygeal area was clipped, and the skin was prepared for aseptic placement of intravascular catheters and an epidural needle. Intravascular catheters and the epidural needle were placed, after in¢ltration of skin and subcutaneous tissues with 2% lidocaine (lidocaine 2% injectable, PhÎnix Scienti¢c Inc., St. Joseph, MO). Epidural needle placement An 18-gauge, 8.75-cm spinal needle (Monoject, Sherwood Medical, St. Louis, MO) was placed into the epidural space along the median plane at the ¢rst coccygeal (Co1-Co2) interspace and slowly advanced rostrad at a 10^30 8 angle to the spinal cord until the interarcuate ligament (ligamentum £avum) was pierced, using the loss of resistance technique for identifying the epidural space (Skarda 1996). Radiographic views of all mares veri¢ed the vertebral location of the needle in situ (Fig. 1). The distance from the skin to the free lumen of the epidural space was Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
TB TB TB TB TB SB SB SB SB SB 15 3
20 25 30 33 34 75 80 143 144 145 Mean SD
14 15 12 14 14 18 20 10 19 18
Age (y) 565 565 560 480 510 475 480 510 485 490 512 37
Body Weight (kg) 7.5 8.7 8.7 8.7 8.7 8.7 7.5 8.7 8.7 8.7 8.5 0.5
Volume of 0.5% ropivacaine (mL) 9 8 8 8 8 8 9 8 8 8 8.2 0.4
Vertebral level of needle tip Co1 ± S5 S5 S5 S5 S5 S5 Co1 ± S5 S5 S5 S5
Time (minutes) of no response to electrical stimulation (> 40 milliamps) at the perineal area. yTime (minutes) of return of sensory perception to electrical stimulation (> 40 milliamps) at the perineal area minus induction time. TB Thoroughbred; SB Standardbred S5, S4, S3, and S2 fifth, fourth, third and second sacral vertebra; Co1 ^ S5 sacrococygealintervertebral space.
Breed
Mare No.
Distance between skin and needle point (cm)
5 5 15 10 5 10 5 15 10 15 10 4
Onset (induction time, minutes)
Analgesia
150 195 165 165 195 260 235 260 180 150 196 42
Duration (recovery timey, minutes)
Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx
to to to to to to to to to to
S4 S2 S3 S2 S4 S3 S4 S3 S2 S3
Dermatome distribution 60 minutes after ropivacaine (Fig. 2)
Table 1 Distance between skin and needle point, vertebral level of needle tip, volume of 0.5% ropivacaine, onset and duration of perineal analgesia, and dermatome distribution of bilateral analgesia
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
63
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Figure 1 Radiograph of the lateral aspect of the sacrococcygeal area of a Standardbred mare (510 kg) with spinal needle in proper position to produce caudal epidural analgesia. The needle is at a 128 angle perpendicular to the spinal cord. S4 4th, S5 5th sacral vertebra; Co1 1st, Co2 2nd coccygeal vertebra. SN 18-gauge, 8.75-cm spinal needle with stylet.
measured by noting the distance between the needle hub and skin puncture site and subtracting the distance from the length of the needle. Correct needle placement was assumed by noting minimal resistance to epidural injection of approximately 2 mL air after piercing the interarcuate ligament and observing the characteristic local anesthetic e¡ects e.g. bilateral perineal analgesia (BPA), decreased tail muscle tone, anal sphincter relaxation, sweating in analgesic zones after ropivacaine administration. Faulty needle placement was assumed if mares demonstrated inadequate perineal analgesia (IPA) after ropivacaine administration. Injections A 0.5% solution of ropivacaine HCl (Naropine Astra, Astra USA, Inc.,Westborough, MA) was injected into the epidural needle. A total volume of 8 or 9 mL of ropivacaine per mare was administered at a rate of approximately 1 mL every 6 seconds. The 8 or 9 mL volume was selected if the needle tip was placed at the ¢fth sacral or sacroccocygeal vertebrae, respectively. In a separate pilot study, we determined that approximately 0.8 mg kg 1 in a volume of 8 mL was the optimal dose-to-volume ratio to produce bilateral perineal analgesia and minimal ataxia in mares (Skarda & Muir 1999). A larger volume (>9 mL) of local anesthetic increased the incidence of successful bilateral perineal analgesia, however, it also 64
increased the degree of ataxia and/or produced recumbency of mares in our pilot study. Assessment of analgesia Analgesia was assessed, using a peripheral nerve stimulator (DigiStim III, Neuro Technology Inc., Houston, TX) and skin and deep muscular pinpricks as described (Skarda & Muir 1983, 1996a). The site of electrical stimulation was consistent after piercing a 20 gauge, 2.5 cm needle through a skin fold on either side of the vulva, approximately 5 cm apart, and attaching an alligator clip electrode to the needle shaft. At least three pulses at a rate of one pulse per 10 seconds, 200 microseconds pulse width and at increments of approximately 5 milliamps current were applied until an avoidance response was observed: purposeful movement of tail, limbs, trunk, head or neck.We were able to ascertain the amperage of the current provided by ¢rst selecting the amperage by turning a knob on the nerve stimulator and then reading the actual applied milliamps as a number displayed on the monitor after stimulation. An analgesic threshold >40 milliamps in the perineal region was used to determine time to onset and duration of analgesia for each treatment (Skarda & Muir 1999). A threshold greater than 40 milliamps seemed to be the average value of milliamps above which all mares did not respond to deep needle pricks at both the left and right perineal areas. A value of 60 Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
milliamps in human beings has been assessed as equivalent to the intensity of stimulation caused by surgical incision (Petersen-Felix et al. 1993; Zbinden et al. 1994). The cut o¡ for the amperage in mares which did not show any avoidance was the maximal output (80 milliamps) of the DigiStim III monitor which was readily set. Super¢cial skin pricks and deep muscular pricks were applied to adjacent dermatomes, starting at the coccyx and moving forward to the sacral region and distal to the pelvic limbs, until an avoidance response was observed to assess the extent of di¡usion of ropivacaine solution within the epidural space. The extent of sensory perception to a needle prick at the coccyx to second sacral dermatomes was assessed (Fig. 2). The most rostral skin area of the mare with no response to deep needle prick 60 minutes after ropivacaine administration was indicated with adhesive tape and was photographed (Fig. 3).
Numerical rating scales were also used to quantify the mares' degree of sedation (head drop), ataxia (position of pelvic limbs) and behavior. The degree of sedation was assessed by observing the mare's head drop. Head drop was scored on a scale of 0^2. A score of 0 was given if there was no change in head position from that in the noninjected mare; scores of 1 and 2 were given if the mare's muzzle was lowered to the cubital (score of 1) and carpal (score of 2) joints, respectively. The degree of ataxia was assessed by use of a numerical scale of 0^2. A score of 0 was given if there was no change in limb position from that of the noninjected mare. A score of 1 was given when the mare was stable but was supporting its weight on 3 limbs or swaying slightly; and a score of 2 was given if the mare was swaying and leaning against the stock, or demonstrated a proprioceptive de¢cit. Behavior was evaluated on a scale 0^3; if the mare was apathetic and indi¡erent (score of 0), friendly
Figure 2 Lateral (A) and caudal (B) drawings of the lumbosacral, sacral and sacrococcygeal areas of a standing mare with marked loss of skin sensation from coccyx to S4 (a), coccyx to S3 (b), and coccyx to S2 (c), respectively, 60 minutes after epidural administration of ropivacaine. E and F, spinal needle placement for caudal epidural anesthesia. L6, sixth lumbar; S1, ¢rst sacral; Co1, ¢rst coccygeal vertebrae. Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
65
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Figure 3 Thoroughbred 560-kg mare with marked area of loss of skin sensation between S2 and coccyx after administration of ropivacaine solution (0.5%, 8 mL) in the epidural space at the 5th sacral vertebra. RE ropivacaine epidural. The site of epidural needle is marked with an arrow.
(score of 1), nervous (score of 2), and very nervous with attempt to move away (score of 3). Scores for each mare were determined at each time period and rated by the same person to avoid any observerdependent subjective di¡erences. Cardiovascular and respiratory measurements An 18-gauge, 30-cm catheter (Vialon polymer resin radiopaque intracath, Deseret Medical Inc., Sandy, UT) was inserted into the left carotid artery as previously described (Skarda & Muir 1996a) to measure systemic arterial blood pressure (ABP [systolic ABP, mean ABP, diastolic ABP, mm Hg]) and anaerobically collect arterial blood samples for pH and blood gas analysis (PO2, PCO2 [mm Hg, kPa]), standard bicarbonate (HCO3^ [mmol L 1]) and standard base excess (BE [mmol L 1]) concentration, PCV [%], hemoglobin (Hb [g dL 1]) and total solids (TS [g dL 1]) concentration. A 30-cm length of 240 polyethylene tubing was inserted into the right external jugular vein. A base-apex ECG was continuously monitored (via surface electrodes) heart rate (HR [beats per minute]) and rhythm. The pressure wave forms were obtained, 66
using a calibrated strain-gauge transducer (Gould Statham Instruments Inc., Hato Ray, Puerto Rico). The pressure transducer used to measure systolic ABP, mean ABP and diastolic ABP was positioned at the level of the scapulohumeral joint and was calibrated against a mercury manometer. Mean ABP was obtained by electronic integration of the signal obtained from the blood pressure transducer. Deep rectal temperature (8C) was continuously measured after placing a thermometer probe (YSI 400 probe tele-thermometer, Scienti¢c Division,Yellow Springs Instrument Co. Inc., Yellow Springs, OH) approximately 20 cm deep into the rectum. Respiratory rate (RR; breaths per minutes) was determined by counting the mares' thoracic and abdominal excursions during 1 minute. Arterial blood samples (2 mL each) were collected anaerobically into heparinized plastic syringes from the carotid artery catheter. The syringes were capped and placed in an iced water bath, and analyzed within 20 minutes of collection for determination of PO2, PCO2 and pH by use of a microprocessor blood gas analyzer (ABL 500-K pH and blood gas analyzer, Radiometer Copenhagen, Copenhagen, Denmark). All blood gas values were Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
corrected for each mare's rectal temperature, measured by the thermometer probe. Packed cell volume and TS concentrations also were measured from these samples. Packed cell volume was determined in duplicate by use of a microhematocrit technique (Criticaps, microhematocrit capillary tube reader, Monoject Scienti¢c, St. Louis, MO); Hb concentration and oxygen saturation (SO2 [%]) were estimated, using a hemoximeter (OSM 3 Radiometer, Copenhagen, West Lake, OH). Total solids concentrations were estimated by use of a refractometer (10436 Veterinary refractometer, Cambridge Instruments, Bu¡alo, NY). Standard bicarbonate and standard BE were calculated. Experimental protocol After placement of catheters, epidural needle, rectal thermometer probe and ECG leads, each mare was allowed to stand undisturbed for at least 60 minutes prior to beginning the experiment. Baseline (time 0) measurements were obtained, just before the ropivacaine was administered epidurally. Hemodynamic and respiratory measurements and scores of analgesia, sedation, ataxia and behavior were obtained before (time 0) and 5, 15, 30, 45, 60, 90, 120, 135, 150, 165, 180, 210, 240, 270 and 300 minutes after epidural administration of ropivacaine. Arterial blood samples were collected before (time 0) and at 30, 60, 90,120,150,180, 210, 240 and 300 minutes after ropivacaine injection. The order of data collection was always evaluation of behavior, measurement of RR and HR, hemodynamic measurements, collection of carotid arterial blood samples and analgesic testing. Analgesic testing was performed after evaluating the degree of sedation and ataxia, and collecting cardiorespiratory data to minimize the e¡ect of stimulation on these variables. The catheters and needle were removed after completion of the study and the mare was walked back to the stall. Mares with inadequate perineal analgesia Mares which responded to needle pricks and electrical stimulation of less than 40 milliamps at the perineal area after ropivacaine administration were judged to have inadequate perineal analgesia. The mares were then injected with the same anesthetic (8 mL of 0.5% ropivacaine hydrochloride solution 500 kg 1) once more on a separate occasion and were re-evaluated for presence or absence of bilateral perineal analgesia (> 40 milliamps current) and Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
responses to needle pricks. At least 10 days elapsed between the injections. Statistical analysis Numerical scores (mean SD) of analgesia, sedation, ataxia, behavior, and cardiovascular and respiratory data were determined in 10 mares with BPA and ¢ve mares with IPA after ropivacaine administration. Analysis of variance (ANOVA) with repeated measures was used to detect signi¢cant di¡erences of mean values from baseline. Dunnett's t-test was used to determine the time at which treatment response differed from baseline. A value of p < 0.05 was considered signi¢cant.
Results Mares with bilateral perineal analgesia (BPA) The distance from the skin of the ¢rst coccygeal interspace to the needle point within the epidural space in 10 mares varied from 7.5 to 8.7 cm (8.5 0.5 cm, mean SD). Epidural administration of 0.5% ropivacaine (8 mL at the 5th sacral vertebrae and 9 mL at the sacrococcygeal vertebrae, respectively) resulted in varying degrees of bilateral analgesia, with dermatomal spread ranging from the coccyx to S4 and from the coccyx to S2 spinal cord segments in adult mares (Table 1). Tests of analgesia by needle prick indicated desensitized dermatomes supplied by the caudal, caudal rectal, perineal and pudendal nerves in all mares. In addition, analgesia of the caudal cutaneous femoral nerves on the right side was induced in one mare (143). This mare became ataxic. Mares responded with avoidance to 2.7 0.5 milliamps (mean SD) at the perineal area before epidural injection. Analgesia to electrical stimulation (> 40 milliamps) at the perineal area was achieved in 5^ 15 minutes (10 4 minutes, mean SD) and lasted 150^260 (196 42 minutes, mean SD) after injection in all mares (Table 1). Lack of avoidance response to maximal electrical stimulation (mean 66.6 16.1 milliamps) at the perineal area was achieved at 15^45 (mean 26 16) minutes and lasted 105^240 (mean157 44) minutes after injection (Fig. 4). Perineal sweating was observed in analgesic zones in all mares. Overall mean scores of the mare's behavior ranged from 0 to 1, with a mean value of 0.8 0.2. Degree of head drop ranged from 0 (no change) to 1 (muzzle at cubital joint), with mean value of 0.13 0.11 in mares. Mean scores of ataxia ranged from 0 67
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Figure 4 Quantitative assessment of perineal analgesia in 10 mares after epidural administration of ropivacaine (0.5%, 8 mL per 500 kg, ~ [bilateral perineal analgesia]) and in ¢ve of these mares after faulty epidural administration of ropivacaine ( [inadequate perineal analgesia]). Data are expressed as mean SD, with 0 milliamps being no analgesia, 40 milliamps being the analgesia threshold and 80 milliamps being the greatest degree of analgesia. Signi¢cant (p < 0.001) di¡erence between groups.
(no change of pelvic limb position) to 1 (slight swaying), with an overall mean value of 0.07 0.06. Cardiovascular and respiratory data Epidural administration of ropivacaine (0.08 mg kg 1) signi¢cantly reduced RR by 51% (p < 0.001) but did not signi¢cantly change HR, ABP, rectal temperature, arterial PO2, PCO2, SO2, pH, standard HCO3^, standard BE, PCV, Hb and TS concentrations (p > 0.05) (Tables 2 and 3). Mares with inadequate perineal analgesia (IPA) Five mares developed IPAand no signi¢cant (p > 0.05) changes of sedation, ataxia, behavior and cardiovascular, and respiratory parameters after ropivacaine administration (Tables 2 and 3). Bilateral perineal analgesia was achieved in the mares after the second ropivacaine administration at least10 days later.
Discussion Results of this study demonstrate that epidural administration of 0.5% ropivacaine hydrochloride solution (8 mL 500 kg 1) is capable of inducing profound and selective sensory blockade of nociceptive and motor ¢bers in dermatomes ranging from coccygeal to the second sacral vertebra within 68
5^15 minutes, and lasting longer than 2.5 hours, with minimal sedation, ataxia, changes of behavior, and cardiopulmonary e¡ects, in conscious adult mares. The reason for ¢ve mares not to demonstrate bilateral perineal analgesia after the ¢rst epidural injection of ropivacaine is speculative. Some ropivacaine could have been administered into the epidural space, but not in su¤cient quantity to bathe the last 2^3 pairs of sacral nerves in the vertebral space to produce bilateral analgesia. Inadequate perineal analgesia can result from improper injection technique, use of solutions of diminished potency and inadequate dispersal of the anesthetic in the epidural space (Skarda 1982). Faulty needle placement such as inappropriate angulation of the needle at the injection site or deviation of the needle from the midline seem to be the most likely causes for poor analgesia of mares in this study, because another needle placement and injection of the same anesthetic (8 mL of 0.5% ropivacaine) did induce BPA on a separate occasion. Inappropriate angulation of the spinal needle at the injection site before injection can be assumed if it can be felt that the needle point has struck the dorsal aspect of the vertebral arch. Deviation of the needle from the midline can be recognized by looking at the caudal aspect of the needle hub and axis of the free needle shaft in relation to the median plane; it also can be felt if the point strikes the transverse process. Asymetric and incomplete analgesia in the mare after proper needle placement into the epidural space is not uncommon (Skarda 1987). It may occur in mares that have anatomic pecularities from previous injections. If such is the case, another injection technique using a longer needle inserted at a lesser angle at a more distant site may provide good results (Fig. 2). It is our clinical experience, however, that unilateral and inadequate analgesia is more probably achieved if the spinal needle has been inserted a considerable distance into the vertebral canal (the actual distance of the needle bevel to the spinal cord), allowing the needle tip to deviate from the midline, and if a small amount of local anesthetic has been given to bathe the nerve roots primarily on one side of the spinal column. A larger volume (> 9 mL) of local anesthetic would have increased the incidence of successful bilateral perineal analgesia, however, it also would have increased the degree of ataxia and/ or produced recumbency of mares. Indications for the use of caudal epidural analgesia include pain relief and control of rectal tenesmus associated with irritation of the perineum, anus, Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Table 2 Cardiovascular and respiratory values (mean SD) from mares after epidural administration of ropivacaine HCl solution Time (minutes) after epidural administration of ropivacaine Variable Heart rate (beats min 1) BPA IPA Systolic arterial pressure (mm Hg) BPA IPA Mean arterial pressure (mm Hg) BPA IPA Diastolic arterial pressure (mm Hg) BPA IPA Respiratory rate (breaths min 1) BPA IPA Rectal temperature (8C) BPA IPA
0
30
34 10 34 7
60
120
180
240
300
32 8 33 9
32 8 31 5
31 7 34 6
31 6 34 6
31 7 35 4
33 10 33 5
144 7 142 7
141 10 135 6
143 14 136 8
141 10 143 8
149 15 143 13
146 12 143 15
147 12 144 13
114 6 114 8
110 9 107 6
113 10 108 7
115 7 118 7
116 11 119 13
117 12 114 10
119 10 117 7
91 6 91 6
92 7 84 5
92 9 87 6
93 11 93 7
97 10 99 12
99 9 95 12
94 12 95 12
29 8 28 10
18 7 20 5
16 5 22 7
14 5 23 3
15 4 20 6
16 5 20 5
15 6 18 6
37.8 0.3 37.7 0.4
37.8 0.3 37.6 0.4
37.7 0.3 37.7 0.4
37.7 0.3 37.6 0.4
37.7 0.3 37.6 0.4
37.7 0.3 37.6 0.4
37.7 0.3 37.6 0.4
BPA bilateral perineal analgesia (n 10); IPA inadequate perineal analgesia (n 5). Significant ( p < 0.05) change from time 0 (baseline). Data for times 5,15, 45,75, 90,105,135,150,165, and 240 minutes are available on request from author.
rectum and vagina during di¤cult labor, correction of uterine torsion, fetotomy and various obstetrical manipulations and surgical procedures such as repairs of recto-vaginal ¢stula, prolapsed rectum, urethrostomy, or anal, perineal, vulvar and bladder procedures in standing horses (Skarda1996). Drugs routinely used for epidural administration in horses include the local anesthetics lidocaine and mepivacaine and the alpha2-adrenoceptor agonists xylazine and detomidine (Skarda & Muir, 1996a, b). These drugs are either too short acting (lidocaine, mepivacaine; 1^2 hours;) or produce ataxia and signi¢cant CNS and cardiovascular depression (xylazine, detomidine). They are all at high risk of producing postural instability, rear limb ataxia, recumbency and excitement in conscious horses. Ropivacaine may be superior to lidocaine and mepivacaine solution for extended surgery in the caudal area of standing mares because of its longer duration of local anesthetic action (2.5 versus 1.5 hours) and may be superior to xylazine and detomidine because it produced more rapid onset of perineal analgesia (10 versus 30 minutes) with less sedation, ataxia, and cardiovascular and respiratory depression. Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
The intrinsic vasoconstrictive property of ropivacaine is of particular interest because vasoconstriction leads to prolonged analgesia and might not require the concomitant use of epinephrine (Kopacz et al. 1989; Guinard et al. 1991; Hurley et al. 1991; Nakamura et al. 1993; Cederholm et al. 1992, 1994; Geradini et al.1995; Koinig et al.1999). Ropivacaine is a commonly used local anesthetic in humans. It produced comparable sensory and sympathetic blockade but produced less intense motor blockade of shorter duration when compared to bupivacaine (Brown et al. 1990; Kerkamp et al. 1990a, 1990b; Brockway et al. 1991; Morrison et al. 1994; Gri¤n & Reynolds 1995). In addition, studies in animals indicate signi¢cantly less central nervous system and cardiac toxicity and dysrhythmogenicity following epidural ropivacaine (Feldman & Covino 1988; Feldman et al.1989,1991,1996; Scott et al.1989; Reiz et al. 1989; Nancarrow et al. 1989; Moller & Covino 1990; Pitkanen et al. 1992; Santos et al. 1999) when compared with bupivacaine. The reason for ropivacaine to be less cardiotoxic and produce less motor block than bupivacaine is not clear, but may be attributable to its S-(^) enantiomer form and lower lipid solubility rather than 69
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Table 3 Arterial acid-base and blood gas values (mean SD) from mares after epidural administration of ropivacaine HCl solution
Variable 0 Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA
Time (minutes) after epidural administration of ropivacaine 30 60 120 180
240
300
pH 7.43 0.02 7.44 0.02 7.44 0.02 7.45 0.02 7.44 0.03 7.44 0.03 oxygen tension (mm Hg) 101.6 7.4 105.4 6.9 105.1 7.9 103.0 3.0 105.4 9.8 102.3 7.8 carbon dioxide tension (mm Hg) 41.1 3.2 40.0 4.2 40.7 2.5 39.9 3.8 40.0 5.5 39.0 5.7 standard bicarbonate (mEq L 1) 26.9 1.4 26.7 1.8 27.0 1.4 26.9 2.2 26.9 2.0 28.0 5.6 standard base excess (mEq L 1) 2.8 1.2 2.9 1.3 3.0 1.4 3.3 1.6 3.1 1.4 2.5 2.0 PCV (%) 35.9 4.0 33.6 3.7 34.3 3.2 35.6 3.0 36.2 4.9 34.0 4.5 total hemoglobin concentration (g dL 1) 11.8 2.3 11.5 2.6 11.4 2.2 12.3 0.7 12.6 2.7 12.6 2.6 oxyhemoglobin saturation (%) 99.7 0.4 100.0 0.4 99.7 0.7 99.8 0.2 99.8 0.5 99.7 0.7 total solids concentration (g dL 1) 6.3 0.5 6.4 0.3 6.3 0.5 5.8 0.3 6.0 0.2 5.9 0.4
7.45 0.02 7.45 0.01
7.44 0.02 7.46 0.02
7.45 0.02 7.44 0.01
7.45 0.03 7.44 0.01
105.8 11.8 104.5 5.0
98.5 9.1 103.9 8.2
103.2 11.2 100.9 5.0
99.9 12.5 100.0 10.5
38.5 4.2 36.1 4.2
40.0 4.0 38.7 2.4
39.9 3.7 38.4 5.4
39.6 3.7 38.8 3.8
26.6 2.3 24.8 3.0
26.6 2.9 27.0 1.7
26.7 2.1 26.6 3.1
27.0 2.4 26.2 2.2
3.1 1.8 2.4 1.5
3.3 1.7 3.4 1.5
2.9 1.8 3.0 2.3
3.3 2.1 2.6 1.6
34.6 3.5 37.5 6.7
32.6 4.9 37.0 2.8
32.5 3.9 35.2 1.7
33.3 3.2 36.4 3.4
12.0 1.3 12.4 3.3
10.7 0.9 12.7 1.2
10.6 1.1 10.5 3.5
11.1 1.6 12.0 2.2
99.8 0.5 99.6 0.6
99.5 0.8 99.7 0.5
99.9 0.6 99.8 0.9
98.5 0.7 99.8 0.6
6.3 0.5 5.9 0.4
6.3 0.6 6.1 0.3
6.2 0.5 5.8 0.3
6.3 0.6 6.1 0.2
BPA bilateral perineal analgesia (n 10); IPA inadequate perineal analgesia (n 5). Data for times 90,150, and 210 minutes are available on request from author.
potency of ropivacaine (Rosenberg et al.1986; DeJong 1995). While both stereo isomers of ropivacaine are similar in their local anesthetic e¡ects, the S-(^) form appears to be less cardiotoxic than its R-() counterpart and less cardiotoxic than equipotent doses of bupivacaine (Etches et al.1997; Santos et al.1999). Dose^response studies to evaluate the potency of epidural ropivacaine and bupivacaine in humans and animals have not been reported. Studies, comparing 0.2^1.0% ropivacaine to 0.2^0.5% bupivacaine describe equipotent analgesia between the local anesthetics (Cederholm et al. 1994; D'A ngelo & James 1999). One study, however, which used an updown sequential allocation study design to estimate the minimum local analgesic concentration (MLAC) or ED50 of ropivacaine and bupivacaine, suggested that epidural ropivacaine was 40% less potent than epidural bupivacaine in patients (Polley et al.1999). 70
Previous clinical studies of ropivacaine in humans have focused on epidural anesthesia and analgesia. These studies used doses of ropivacaine ranging from 100 to 200 mg in varying concentration (0.25, 0.5, 0.75, 1.0%) and produced sensory anesthesia of equally long duration to that produced by bupivacaine but with less profound motor block (Gri¤n & Reynolds 1995; Katz et al. 1990; Kerkamp et al. 1990a). Results of epidural administration of ropivacaine in 900 patients undergoing general surgery have indicated that doses of 100^200 mg of ropivacaine achieved sensory block to the level of T10 in10 (range 5^13) minutes and that the median duration of e¡ect at the T10 level was 4 (range 3^5) hours. Higher doses produced a more profound block with a greater duration of e¡ect (Brown et al. 1990; Alahuhta et al. 1995; Schug et al. 1996). Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Doses of 400 mg and 450 mg of ropivacaine were administered to healthy mares, in the study reported here in which no surgery was performed, producing perineal analgesia to percutaneous electrical nerve stimulation (mean,66.6 16.1 milliamps) within 15^ 45 (mean, 26.4 15.5) minutes, and analgesia lasted 3 (2.5^4) hours. Percutaneous electrical stimulation of the perineum and needle pricks at sacral dermatomes, respectively, in mares can only mimic the intensity of surgical incision, even though previous studies in humans have shown that transcutaneous electrical stimulation at 60 milliamps was equivalent to the intensity of stimulation caused by surgical incisions (Petersen-Felix et al.1993; Zbinden et al. 1994). Epidural administration of 0.5% ropivacaine for caesarean section did not compromise the uteroplacental and fetal circulation in healthy parturient women with uncomplicated pregnancies (Alahuhta et al.1995). The e¤cacy of ropivacaine and bupivacaine for producing lumbar epidural anesthesia in dogs has been compared (Feldman et al. 1988, 1996; Hurley et al.1991; Duke et al.1999, 2000).Various concentrations of ropivacaine (0.25, 0.5, 0.75, 1%) and bupivacaine (0.25, 0.5, 0.75%) using a constant 3-mL epidural volume of ropivacaine and bupivacaine were used. There were no signs of adverse reactions, irreversible block or other sequelae in any of the dogs. Solutions of 0.25% ropivacaine and 0.25% bupivacaine failed to induce complete loss of weight support (mean weight 18.7 1.4 kg) following epidural injection. Onset of motor blockade varied between 5 and 9 minutes, with the use of higher concentrations (> 0.25%), and was inversely related to dose. Duration of motor blockade ranged from 141 minutes (0.5% ropivacaine) to 258 minutes (0.75% bupivacaine). The similar onset times for both drugs are related to their similar pKa values (ropivacaine, 8.0; bupivacaine,8.1) and that theyare both weak bases. Epidural ropivacaine and bupivacaine at similar volumes of 0.5% and 0.75% had similar sensory blockade and cardiopulmonary e¡ects in dogs. The higher concentration of both drugs at 0.22 mL kg 1 appeared to contribute to greater success of block (> 80%) at dermatomes L5 to L7 compared to 67% success with the other groups (Duke et al.1999, 2000). Recently, the e¤cacy of caudal (Co1-Co2) epidural administration of 1% ropivacaine, 2% lidocaine, and combination of 1% ropivacaine and 2% lidocaine for producing perineal anesthesia in 6 mares (320 24 kg) has been compared (Luna et al. 2000). All Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
anesthetics were combined with adrenaline 1 : 200 000 and given at a volume of 0.018 mL kg 1. The times to onset of anesthesia as evaluated by lack of response to painful stimulation of the perineum and vulva using forceps after injection of ropivacaine, lidocaine, and the mixture of ropivacaine and lidocaine were 17 7,15 5, and 7 1 minutes and perineal anesthesia lasted 285 32, 163 27, and 202 34 minutes, respectively. Three mares became recumbent, two received lidocaine and one received the combination of ropivacaine and lidocaine.When comparing these results to our study, the increased duration of perineal anesthesia (285 32 versus 195 42 minutes) and high incidence of ataxia (4 2) using a visual analogue scale from zero (no ataxia) to 10 (recumbency) was probably attributable to the higher concentration (1% versus 0.5%), larger volume (0.018 versus 0.016 mL kg 1), and admixture of adrenaline 1 : 200 000 administered to mares of the referenced study (Luna et al. 2000). Results of this study indicate that injection of ropivacaine (0.5%, 8 mL 500 kg 1) into the caudal epidural space induces prolonged (>2.5 hours) perineal analgesia with minimal sedation, ataxia, and no circulatory and respiratory disturbances in conscious standing mares. The advantages of ropivacaine 0.5% warrant further investigation, particularly under surgical conditions.
Acknowledgements This study was supported in part by Equine Research Funds of the College of Veterinary Medicine,The Ohio State University, USA. Presented in part at the 24th Annual Meeting of the American College of VeterinaryAnesthesiologists, Dallas,Texas. The authors thank Dr Jean Powers for statistical analysis and Jennifer Gadawski, Cheri Edwards and Steve Schumacher for technical assistance.
References Albright GA (1979) Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51, 285^287. Ðkerman B, Hellberg IB,Trossvik C (1988) Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand 32,571^578. Alahuhta S, Ra«sa«nen J, Jouppila P et al. (1995) The e¡ects of epidural ropivacaine and bupivacaine for cesarean section on uteroplacental and fetal circulation. Anesthesiology 83, 23^32. 71
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Brockway MS, Bannister J, McClure JH et al. (1991) Comparison of extradural ropivacaine and bupivacaine. Br J Anaesth 66,31^37. Brodner G, Mertes N, Van Aken H et al. (1999) Epidural analgesia with local anesthetics after abdominal surgery: earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine. Anesth Analg 88,128^133. Brown DL, Carpenter RL,Thompson GE (1990) Comparison of 0.5% ropivacaine and 0.5% bupivacaine for epidural anesthesia in patients undergoing lower-extremity surgery. Anesthesiology 72,633^636. Cederholm I, Evers H, Lofstrom JB (1992) Skin blood £ow after intradermal injection of ropivacaine in various concentrations with and without epinephrine evaluated by Doppler £owmetry. Reg Anesth17,322^328. Cederholm I, Anskar S, Bengtsson M (1994) Sensory, motor, and sympathetic block during epidural analgesia with 0.5% and 0.75% ropivacaine with and without epinephrine. Reg Anesth19,18^33. Cohen S, Hronkova B, Croitoru M et al. (1999) What is the optimal concentration of ropivacaine for continuous epidural infusion for labor pain? Anesthesiology 90, A32(Abstract). D'A ngelo R, James RL (1999) Is ropivacaine less potent than bupivacaine? Anesthesiology 90,941^943. DeJong RH (1995) 1995 Gaston Labat Lecture. Ropivacaine. White knight or dark horse ? Reg Anesth 20, 474^481. Duke T, Caulkett NA, Ball SD et al. (1999) Comparative analgesic and cardiopulmonary e¡ects of epidural bupivacaine and ropivacaine in conscious dogs. Proceedings of the 24th Annual Meeting of the American College of VeterinaryAnesthesiologists, Dallas,Texas. p12. Duke T, Caulkett NA, Ball SD et al. (2000) Comparative analgesic and cardiopulmonary e¡ects of bupivacaine and ropivacaine in the epidural space of the conscious dog. Vet Anaesthesia Analgesia 27,13^21. Etches RC, Writer WDR, Ansley D et al. (1997) Continuous epidural ropivacaine 0.2% for analgesia after lower abdominal surgery. Anesth Analg 84,784^790. Feldman HS, Arthur GR, Covino BG (1989) Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesth Analg 69,794^801. Feldman HS, Arthur GR, Pitkanen M et al. (1991) Treatment of systemic toxicity after rapid intravenous injection of ropivacaine and bupivacaine in conscious dogs. Anesth Analg 73,373^384. Feldman HS, Covino BG (1988) Comparative motor-blocking e¡ects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg 67,1047^1052. Feldman HS, Dvoskin S, Arthur GR et al. (1996)Antinociceptive and motor-blocking e¤cacy of ropivacaine and bupivacaine after epidural administration in the dog. Reg Anesth 21,318^326.
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Gautier P, De Kock M, Van Steenberge A et al. (1999) A double-blind comparison of 0.125% ropivacaine with sufentanil and 0.125% bupivacaine with sufentanil for epidural labor analgesia. Anesthesiology 90,772^778. Geradini G, Samuelson U, JernbeckJ et al. (1995) Comparison of vascular e¡ects of ropivacaine on isolated rings of human arteries. Acta Anaesthesiol Scand 39,765^768. Gri¤n RP, Reynolds F (1995) Extradural anaesthesia for caesarean section: a double-blind comparison of 0.5% ropivacaine with 0.5% bupivacaine. Br J Anaesth 74,512^516. Guinard JP, Carpenter RL, Owens BD et al. (1991) Comparison between ropivacaine and bupivacaine after subcutaneous injection in pigs: cutaneous blood £ow and surgical bleeding. Reg Anesth16, 268^271. Hartmannsgruber MWB, Silverman DG, Halaszynski TM et al. (1999) Comparison of ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in volunteers. Anesth Analg 89,727^731. Hurley RJ, Feldman HS, Latka C et al. (1991) The e¡ects of epinephrine on the anesthetic and hemodynamic properties of ropivacaine and bupivacaine after epidural administration in the dog. Reg Anesth16,303^308. Kampe S,Weigand C, Kaufmann J et al. (1999) Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement. Anesth Analg 89,395^398. Katz JA, Knarr D, Brindenbaugh PO (1990) A double-blind comparison of 0.5% bupivacaine and 0.75% ropivacaine administered epidurally in humans. Reg Anesth 15, 250^252. Kerkamp HE, Gielen MJ, EdstrÎm HH (1990a) Comparison of 0.75% ropivacaine with epinephrine and 0.75% bupivacaine with epinephrine in lumbar epidural anesthesia. Reg Anesth15, 204^207. Kerkamp HE, Gielen MJ, Wattwil M et al. (1990b) An open study comparison of 0.5%, 0.75% and 1.0% ropivacaine, with epinephrine, in epidural anesthesia in patients undergoing urologic surgery. Reg Anesth15,53^58. Klein SM, Greengrass RA, Steele SM et al. (1998) A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block. Anesth Analg 87,1316^1319. Knudsen K, SuurkÏla MBB, Blomberg S et al. (1997) Central nervous and cardiovascular e¡ects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 78,507^514. Koinig H, Krenn CG, Glaser C et al. (1999) The dose^response of caudal ropivacaine in children. Anesthesiology 90, 1339^1344. Kopacz DJ, Carpenter RL, Mackey DC (1989) E¡ect of ropivacaine on cutaneous capillary blood £ow in pigs. Anesthesiology 71,69^74. Liu SS, Moore JM, Luo AM et al. (1999) Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia. Anesthesiology 90,727^733.
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Luna SPL, Bueno SK, Cruz ML et al. (2000) Extradural anaesthesia using lidocaine, ropivacaine, hyperbaric lidocaine and a combination of lidocaine and ropivacaine in mares.Vet Anaesthesia Analgesia 27,57(Abstract). Moller R, Covino BG (1990) Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic.Anesthesiology 72,322^329. Morrison LM, Emanuelsson BM, McClure JH et al. (1994) E¤cacy and kinetics of extradural ropivacaine: a comparison with bupivacaine. Br J Anaesth 72,164^169. Nakamura K,Toda H, Kakuyama M, et al. (1993) Direct vascular e¡ects of ropivacaine in femoral artery and vein of the dog. Acta Anaesthesiol Scand 37, 269^273. Nancarrow C, Rutten AJ, RuncimanWB et al. (1989) Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg 69, 276^283. Owen MD, D'A ngelo R, Gerancher JC et al. (1998) 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled epidural infusion. Anesth Analg 86,527^531. Petersen-Felix S, Zbinden AM, Fischer M et al. (1993) Iso£urane minimum alveolar concentration decreases during anesthesia and surgery. Anesthesiology 79,959^965. Pitkanen M, Feldman HS, Arthur GR et al. (1992) Chronotropic and inotropic e¡ects of ropivacaine, bupivacaine, and lidocaine in the spontaneously beating and electrically paced isolated, perfused rabbit heart. Reg Anesth 17,183^192. Polley LS, Columb MO, Naughton NN et al. (1999) Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor. Anesthesiology 90, 944^950. Reiz S, Ha«ggamark S, Johansson G et al. (1989) Cardiotoxicity of ropivacaine ^ a new amide local anaesthetic agent. Acta Anaesthesiol Scand 33,93^98. Rosenberg PH, Kytta« A, Alila A (1986) Absorption of bupivacaine, etidocaine, lidocaine and ropivacaine into nheptane, rat sciatic nerve, and human extradural and subcutaneous fat. Br J Anaesth 58,310^314. Santos AC, Karpel B, Noble G (1999) The placental transfer and fetal e¡ects of levobupivacaine, racemic bupivacaine, and ropivacaine. Anesthesiology 90,1698^1703. Santos AC, Arthur GR, Wlody D et al. (1995) Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes. Anesthesiology 82, 734^740. Schug SA, Scott DA, Payne J et al. (1996) Postoperative analgesia by continuous extradural infusion of ropivacaine after upper abdominal surgery. Br J Anaesth 76, 487^491. Scott DA, Blake D, Buckland M et al. (1999) A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 mg/mL fentanyl for seventy-two hours of
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
postoperative analgesia after major abdominal surgery. Anesth Analg 88,857^864. Scott DA, Chamley DM, Mooney PH et al. (1995) Epidural ropivacaine infusion for postoperative analgesia after major lower abdominal surgery ^ a dose ¢nding study. Anesth Analg 81,982^986. Scott DB, Lee A, Fagan D et al. (1989) Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 69,563^569. Scrutton MJ, Srikantharajah I,Williams H et al. (1998) Comparison of ropivacaine with bupivacaine for epidural analgesia in labor. Anesth Analg 81, A34(Abstract). Skarda RT (1982) Practical regional anesthesia. In. Equine Medicine and Surgery (3rd edn). Mansmann RA, McAllister ES, Pratt PW (eds). AmericanVeterinary Publications, Santa Barbara, CA, pp. 228^249. Skarda RT (1987) Local and regional analgesia. In: Principles and Practice of Veterinary Anesthesia. Short CE (ed. ).Williams & Wilkins, Baltimore, MD, pp.91^133. Skarda RT (1996) Local and Regional Analgesic Techniques. B. Horses. In: Lumb and Jones' Veterinary Anesthesia. Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins, Baltimore, MD, pp. 448^478. Skarda RT, MuirWW (1983) Continuous caudal epidural and subarachnoid anesthesia in mares: a comparative study. Am J Vet Res 44, 2290^2298. Skarda RT, MuirWW (1996a) Analgesic, hemodynamic, and respiratory e¡ects of caudal epidurallyadministered xylazine hydrochloride solution in mares. Am J Vet Res 57, 193^200. Skarda RT, Muir WW (1996b) Comparison of antinociceptive, cardiovascular, and respiratory e¡ects, head ptosis, and position of pelvic limbs in mares after caudal epidural administration of xylazine and detomidine hydrochloride solution. Am J Vet Res 57,1338^1345. Skarda RT, Muir WW (1999) Analgesic, hemodynamic and respiratory e¡ects of caudal epidurally administered ropivacaine hydrochloride solution in mares. Proceedings of the 24th Annual Meeting of the American College of VeterinaryAnesthesiologists, Dallas,Texas.p.14. Tuttle AA, Katz JA, Brindenbaugh PO et al. (1995) A doubleblind comparison of the abdominal wall relaxation produced by epidural 0.75% ropivacaine and 0.75% bupivacaine in gynecologic surgery. Reg Anesth 20, 515^520. Vallejo M, Mandell G, Makishima S et al. (1999a) Walking epidural ropivacaine analgesia during labor. Anesthesiology 90, A37(Abstract). Vallejo M, Mandell G, Makishima S et al. (1999b) E¤cacy of 0.05% ropivacaine for walking labor epidural analgesia. Anesthesiology 90, A38(Abstract). Wicks TC (1995) Ropivacaine: an introduction to a new local anesthetic. CRNA 6,129^134. Zaric D, Nydahl PA, Philipson L et al. (1996) The e¡ect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25% bupivacaine on sensory and
73
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir motor block in volunteers: a double-blind study. Reg Anesth 21,14^25. Zbinden AM, Maggiorini M, Petersen-Felix S et al. (1994) Anesthetic depth de¢ned using multiple noxious stimuli during iso£urane/oxygen anesthesia: I. Motor reactions. Anesthesiology 80, 253^260.
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Zwack R, Campbell DC, Sawatzky K et al. (1999) Ambulatory labor epidural analgesia: bupivacaine versus ropivacaine. Anesthesiology 81, A899 (poster).
Received 22 December1999, Accepted1 March 2000.
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
Analgesic, hemodynamic and respiratory effects of caudal epidurally administered ropivacaine hydrochloride in mares Roman T Skarda
Dr. med. vet., PhD, Dip ACVA, Dip ECVA;
William W Muir
DVM, PhD, Dip ACVA, Dip ACVECC
Department of Veterinary Clinical Sciences,The Ohio State University,601 Vernon L. Tharp Street, Columbus, Ohio 43210^1089, USA
Correspondence: R. T. Skarda, Department of Veterinary Clinical Sciences,The Ohio State University, 601 Vernon L. Tharp Street, Columbus, Ohio 43210^1089, USA
Abstract Objective To determine the analgesic, hemodynamic and respiratory e¡ects, sedation and ataxia in mares of caudal epidural administration of ropivacaine hydrochloride solution. Study design Prospective, single-dose trial. Animals Ten healthy mares weighing from 475 to 565 kg. Methods Intravascular catheters and an epidural needle were placed after in¢ltration of the skin and subcutaneous tissues with 2% lidocaine. Ropivacaine (0.5%, 8 or 9 mL) was then injected epidurally at the ¢fth sacral or sacrococcygeal vertebrae, respectively. Analgesia was determined by lack of sensory perception to electrical stimulation (> 40 milliamps) and absence of response to needle pricks extending from coccyx to S2 dermatomes. Electrocardiogram, heart and respiratory rates, rectal temperature, arterial blood pressure, arterial acid-base (pH, standard bicarbonate and base excess), gas tensions (PO2, PCO2), PCV, oxyhemoglobin and total solids concentrations, and numerical scores of perineal analgesia, sedation (head drop), and ataxia (position of pelvic limbs) were determined before and during a 5-hour testing period. Analysis of variance (ANOVA) with repeated measures was used to detect signi¢cant (p < 0.05) di¡erences of mean values from baseline.
Results Epidurally administered ropivacaine induced variable analgesia extending bilaterally from coccyx to S2 (three mares), coccyx to S3 (four mares), and coccyx to S4 (three mares), with minimal sedation, ataxia, and cardiovascular and respiratory disturbances of mares. Perineal analgesia was attained at 10 4 minutes and lasted for 196 42 minutes (mean SD). Five mares demonstrated inadequate perineal analgesia, probably attributable to deviation of the spinal needle from the midline. They were successfully blocked with ropivacaine on another occasion. Epidural ropivacaine signi¢cantly reduced repiratory rates of mares and did not change other variables from baseline. Conclusions and clinical relevance Ropivacaine (0.5%, 8 mL 500 kg 1) can be administered caudal epidurally to produce prolonged (> 2.5 hours) bilateral perineal analgesia with minimal sedation, ataxia, and circulatory and respiratory disturbances in standing mares. Keywords caudal epidural, mares, ropivacaine.
Introduction The local anesthetics lidocaine and mepivacaine and the alpha2-adrenoceptor agonists xylazine and detomidine are routinely used for epidural administration in horses. These drugs are either too short 61
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
acting (lidocaine, mepivacaine;1^2 hours;) or produce ataxia and signi¢cant CNS and cardiovascular depression (xylazine, detomidine) in mares (Skarda & Muir 1983; 1996a; 1996b). They have the potential to produce postural instability, rear limb ataxia, recumbency and excitement in horses contributing to increased morbidity and mortality (Skarda1996). Death or cardiotoxicity in human obstetric patients, probably after unintentional intravascular administration of bupivacaine or etidocaine, prompted the search for drugs with less cardiotoxicity (Albright1979; Nancarrow et al.1989; Alahuhta et al. 1995; Knudsen et al.1997). Ropivacaine is the newest member of the amino-amide class of long-acting local anesthetics to be introduced and become commercially available in more than 25 years. It is structurally related to, but unlike bupivacaine and mepivacaine, which are supplied commercially as racemic mixtures of two stereo-isomers, ropivacaine is provided as the hydrochloride of the pure S-(^) enantiomer (DeJong 1995; Etches et al. 1997). Ropivacaine blocks the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation, and reducing the rate of rise of the action potential (Ðkerman et al. 1988; Wicks 1995). Epidurally and intravenously administered ropivacaine have been studied for surgical anesthesia (Kerkamp et al. 1990b; Schug et al. 1996; Klein et al. 1998; Hartmannsgruber et al. 1999), acute postoperative pain management (Scott et al. 1995, 1999; Schug et al. 1996; Brodner et al. 1999; Liu et al. 1999; Kampe et al. 1999), and obstetrical procedures in human beings (Brown et al. 1990; Alahuhta et al. 1995; Gri¤n & Reynolds1995;Tuttle et al.1995; Owen et al. 1998; Scrutton et al. 1998; Zwack et al. 1999; Brodner et al. 1999; Cohen et al. 1999; Gautier et al. 1999; Polley et al. 1999; Santos et al. 1999; Vallejo et al. 1999a, b). Clinical trials in volunteers and patients suggest that ropivacaine is similar to bupivacaine in onset, depth, duration and extent of sensory blockade, although motor block is less intense and of shorter duration (Kerkamp & Gielen 1990a; Brockway et al. 1991; Gri¤n & Reynolds 1995; Zaric et al. 1996; Etches et al. 1997; D'A ngelo & James 1999; Koinig et al.1999). An abstract about the onset, duration and ataxia of epidurally administered ropivacaine (1% solution) in six mares (320 24 kg) has recently been reported (Luna et al. 2000). We hypothesized that epidurally administered ropivacaine (0.5% solution) would provide profound and long-lasting (2^4 hours) perineal 62
analgesia with only minimal sedation and ataxia, changes in behavior or cardiovascular and respiratory depression in mares.
Materials and methods Mares The study protocol was approved by the Ohio State University Institutional Animal Care and Use Committee. Ten healthy mares (¢ve Thoroughbreds, ¢ve Standardbreds) from 10 to 20 years old weighing 475^565 kg (Table 1) were studied to assess analgesic, systemic hemodynamic and respiratory e¡ects, sedation and ataxia in mares after the epidural administration of ropivacaine hydrochloride solution. Mare preparation The left carotid artery had been surgically elevated to a subcutaneous position in all mares at least 10 weeks prior to the study. Other surgical procedures were not performed on the mares. All mares were considered healthy on the basis of the results of physical examination, WBC count, and ECG. The mares were allowed ad libitum access to food and water until the beginning of each experiment. All trials were performed between 0900 and 1700 hours in a quiet, climate-controlled room. Mares were standing in restraining stocks for the duration of the study. The hair over the area of the mares' left carotid artery, right jugular furrow and sacrococcygeal area was clipped, and the skin was prepared for aseptic placement of intravascular catheters and an epidural needle. Intravascular catheters and the epidural needle were placed, after in¢ltration of skin and subcutaneous tissues with 2% lidocaine (lidocaine 2% injectable, PhÎnix Scienti¢c Inc., St. Joseph, MO). Epidural needle placement An 18-gauge, 8.75-cm spinal needle (Monoject, Sherwood Medical, St. Louis, MO) was placed into the epidural space along the median plane at the ¢rst coccygeal (Co1-Co2) interspace and slowly advanced rostrad at a 10^30 8 angle to the spinal cord until the interarcuate ligament (ligamentum £avum) was pierced, using the loss of resistance technique for identifying the epidural space (Skarda 1996). Radiographic views of all mares veri¢ed the vertebral location of the needle in situ (Fig. 1). The distance from the skin to the free lumen of the epidural space was Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
TB TB TB TB TB SB SB SB SB SB 15 3
20 25 30 33 34 75 80 143 144 145 Mean SD
14 15 12 14 14 18 20 10 19 18
Age (y) 565 565 560 480 510 475 480 510 485 490 512 37
Body Weight (kg) 7.5 8.7 8.7 8.7 8.7 8.7 7.5 8.7 8.7 8.7 8.5 0.5
Volume of 0.5% ropivacaine (mL) 9 8 8 8 8 8 9 8 8 8 8.2 0.4
Vertebral level of needle tip Co1 ± S5 S5 S5 S5 S5 S5 Co1 ± S5 S5 S5 S5
Time (minutes) of no response to electrical stimulation (> 40 milliamps) at the perineal area. yTime (minutes) of return of sensory perception to electrical stimulation (> 40 milliamps) at the perineal area minus induction time. TB Thoroughbred; SB Standardbred S5, S4, S3, and S2 fifth, fourth, third and second sacral vertebra; Co1 ^ S5 sacrococygealintervertebral space.
Breed
Mare No.
Distance between skin and needle point (cm)
5 5 15 10 5 10 5 15 10 15 10 4
Onset (induction time, minutes)
Analgesia
150 195 165 165 195 260 235 260 180 150 196 42
Duration (recovery timey, minutes)
Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx Coccyx
to to to to to to to to to to
S4 S2 S3 S2 S4 S3 S4 S3 S2 S3
Dermatome distribution 60 minutes after ropivacaine (Fig. 2)
Table 1 Distance between skin and needle point, vertebral level of needle tip, volume of 0.5% ropivacaine, onset and duration of perineal analgesia, and dermatome distribution of bilateral analgesia
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
63
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Figure 1 Radiograph of the lateral aspect of the sacrococcygeal area of a Standardbred mare (510 kg) with spinal needle in proper position to produce caudal epidural analgesia. The needle is at a 128 angle perpendicular to the spinal cord. S4 4th, S5 5th sacral vertebra; Co1 1st, Co2 2nd coccygeal vertebra. SN 18-gauge, 8.75-cm spinal needle with stylet.
measured by noting the distance between the needle hub and skin puncture site and subtracting the distance from the length of the needle. Correct needle placement was assumed by noting minimal resistance to epidural injection of approximately 2 mL air after piercing the interarcuate ligament and observing the characteristic local anesthetic e¡ects e.g. bilateral perineal analgesia (BPA), decreased tail muscle tone, anal sphincter relaxation, sweating in analgesic zones after ropivacaine administration. Faulty needle placement was assumed if mares demonstrated inadequate perineal analgesia (IPA) after ropivacaine administration. Injections A 0.5% solution of ropivacaine HCl (Naropine Astra, Astra USA, Inc.,Westborough, MA) was injected into the epidural needle. A total volume of 8 or 9 mL of ropivacaine per mare was administered at a rate of approximately 1 mL every 6 seconds. The 8 or 9 mL volume was selected if the needle tip was placed at the ¢fth sacral or sacroccocygeal vertebrae, respectively. In a separate pilot study, we determined that approximately 0.8 mg kg 1 in a volume of 8 mL was the optimal dose-to-volume ratio to produce bilateral perineal analgesia and minimal ataxia in mares (Skarda & Muir 1999). A larger volume (>9 mL) of local anesthetic increased the incidence of successful bilateral perineal analgesia, however, it also 64
increased the degree of ataxia and/or produced recumbency of mares in our pilot study. Assessment of analgesia Analgesia was assessed, using a peripheral nerve stimulator (DigiStim III, Neuro Technology Inc., Houston, TX) and skin and deep muscular pinpricks as described (Skarda & Muir 1983, 1996a). The site of electrical stimulation was consistent after piercing a 20 gauge, 2.5 cm needle through a skin fold on either side of the vulva, approximately 5 cm apart, and attaching an alligator clip electrode to the needle shaft. At least three pulses at a rate of one pulse per 10 seconds, 200 microseconds pulse width and at increments of approximately 5 milliamps current were applied until an avoidance response was observed: purposeful movement of tail, limbs, trunk, head or neck.We were able to ascertain the amperage of the current provided by ¢rst selecting the amperage by turning a knob on the nerve stimulator and then reading the actual applied milliamps as a number displayed on the monitor after stimulation. An analgesic threshold >40 milliamps in the perineal region was used to determine time to onset and duration of analgesia for each treatment (Skarda & Muir 1999). A threshold greater than 40 milliamps seemed to be the average value of milliamps above which all mares did not respond to deep needle pricks at both the left and right perineal areas. A value of 60 Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
milliamps in human beings has been assessed as equivalent to the intensity of stimulation caused by surgical incision (Petersen-Felix et al. 1993; Zbinden et al. 1994). The cut o¡ for the amperage in mares which did not show any avoidance was the maximal output (80 milliamps) of the DigiStim III monitor which was readily set. Super¢cial skin pricks and deep muscular pricks were applied to adjacent dermatomes, starting at the coccyx and moving forward to the sacral region and distal to the pelvic limbs, until an avoidance response was observed to assess the extent of di¡usion of ropivacaine solution within the epidural space. The extent of sensory perception to a needle prick at the coccyx to second sacral dermatomes was assessed (Fig. 2). The most rostral skin area of the mare with no response to deep needle prick 60 minutes after ropivacaine administration was indicated with adhesive tape and was photographed (Fig. 3).
Numerical rating scales were also used to quantify the mares' degree of sedation (head drop), ataxia (position of pelvic limbs) and behavior. The degree of sedation was assessed by observing the mare's head drop. Head drop was scored on a scale of 0^2. A score of 0 was given if there was no change in head position from that in the noninjected mare; scores of 1 and 2 were given if the mare's muzzle was lowered to the cubital (score of 1) and carpal (score of 2) joints, respectively. The degree of ataxia was assessed by use of a numerical scale of 0^2. A score of 0 was given if there was no change in limb position from that of the noninjected mare. A score of 1 was given when the mare was stable but was supporting its weight on 3 limbs or swaying slightly; and a score of 2 was given if the mare was swaying and leaning against the stock, or demonstrated a proprioceptive de¢cit. Behavior was evaluated on a scale 0^3; if the mare was apathetic and indi¡erent (score of 0), friendly
Figure 2 Lateral (A) and caudal (B) drawings of the lumbosacral, sacral and sacrococcygeal areas of a standing mare with marked loss of skin sensation from coccyx to S4 (a), coccyx to S3 (b), and coccyx to S2 (c), respectively, 60 minutes after epidural administration of ropivacaine. E and F, spinal needle placement for caudal epidural anesthesia. L6, sixth lumbar; S1, ¢rst sacral; Co1, ¢rst coccygeal vertebrae. Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
65
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Figure 3 Thoroughbred 560-kg mare with marked area of loss of skin sensation between S2 and coccyx after administration of ropivacaine solution (0.5%, 8 mL) in the epidural space at the 5th sacral vertebra. RE ropivacaine epidural. The site of epidural needle is marked with an arrow.
(score of 1), nervous (score of 2), and very nervous with attempt to move away (score of 3). Scores for each mare were determined at each time period and rated by the same person to avoid any observerdependent subjective di¡erences. Cardiovascular and respiratory measurements An 18-gauge, 30-cm catheter (Vialon polymer resin radiopaque intracath, Deseret Medical Inc., Sandy, UT) was inserted into the left carotid artery as previously described (Skarda & Muir 1996a) to measure systemic arterial blood pressure (ABP [systolic ABP, mean ABP, diastolic ABP, mm Hg]) and anaerobically collect arterial blood samples for pH and blood gas analysis (PO2, PCO2 [mm Hg, kPa]), standard bicarbonate (HCO3^ [mmol L 1]) and standard base excess (BE [mmol L 1]) concentration, PCV [%], hemoglobin (Hb [g dL 1]) and total solids (TS [g dL 1]) concentration. A 30-cm length of 240 polyethylene tubing was inserted into the right external jugular vein. A base-apex ECG was continuously monitored (via surface electrodes) heart rate (HR [beats per minute]) and rhythm. The pressure wave forms were obtained, 66
using a calibrated strain-gauge transducer (Gould Statham Instruments Inc., Hato Ray, Puerto Rico). The pressure transducer used to measure systolic ABP, mean ABP and diastolic ABP was positioned at the level of the scapulohumeral joint and was calibrated against a mercury manometer. Mean ABP was obtained by electronic integration of the signal obtained from the blood pressure transducer. Deep rectal temperature (8C) was continuously measured after placing a thermometer probe (YSI 400 probe tele-thermometer, Scienti¢c Division,Yellow Springs Instrument Co. Inc., Yellow Springs, OH) approximately 20 cm deep into the rectum. Respiratory rate (RR; breaths per minutes) was determined by counting the mares' thoracic and abdominal excursions during 1 minute. Arterial blood samples (2 mL each) were collected anaerobically into heparinized plastic syringes from the carotid artery catheter. The syringes were capped and placed in an iced water bath, and analyzed within 20 minutes of collection for determination of PO2, PCO2 and pH by use of a microprocessor blood gas analyzer (ABL 500-K pH and blood gas analyzer, Radiometer Copenhagen, Copenhagen, Denmark). All blood gas values were Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
corrected for each mare's rectal temperature, measured by the thermometer probe. Packed cell volume and TS concentrations also were measured from these samples. Packed cell volume was determined in duplicate by use of a microhematocrit technique (Criticaps, microhematocrit capillary tube reader, Monoject Scienti¢c, St. Louis, MO); Hb concentration and oxygen saturation (SO2 [%]) were estimated, using a hemoximeter (OSM 3 Radiometer, Copenhagen, West Lake, OH). Total solids concentrations were estimated by use of a refractometer (10436 Veterinary refractometer, Cambridge Instruments, Bu¡alo, NY). Standard bicarbonate and standard BE were calculated. Experimental protocol After placement of catheters, epidural needle, rectal thermometer probe and ECG leads, each mare was allowed to stand undisturbed for at least 60 minutes prior to beginning the experiment. Baseline (time 0) measurements were obtained, just before the ropivacaine was administered epidurally. Hemodynamic and respiratory measurements and scores of analgesia, sedation, ataxia and behavior were obtained before (time 0) and 5, 15, 30, 45, 60, 90, 120, 135, 150, 165, 180, 210, 240, 270 and 300 minutes after epidural administration of ropivacaine. Arterial blood samples were collected before (time 0) and at 30, 60, 90,120,150,180, 210, 240 and 300 minutes after ropivacaine injection. The order of data collection was always evaluation of behavior, measurement of RR and HR, hemodynamic measurements, collection of carotid arterial blood samples and analgesic testing. Analgesic testing was performed after evaluating the degree of sedation and ataxia, and collecting cardiorespiratory data to minimize the e¡ect of stimulation on these variables. The catheters and needle were removed after completion of the study and the mare was walked back to the stall. Mares with inadequate perineal analgesia Mares which responded to needle pricks and electrical stimulation of less than 40 milliamps at the perineal area after ropivacaine administration were judged to have inadequate perineal analgesia. The mares were then injected with the same anesthetic (8 mL of 0.5% ropivacaine hydrochloride solution 500 kg 1) once more on a separate occasion and were re-evaluated for presence or absence of bilateral perineal analgesia (> 40 milliamps current) and Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
responses to needle pricks. At least 10 days elapsed between the injections. Statistical analysis Numerical scores (mean SD) of analgesia, sedation, ataxia, behavior, and cardiovascular and respiratory data were determined in 10 mares with BPA and ¢ve mares with IPA after ropivacaine administration. Analysis of variance (ANOVA) with repeated measures was used to detect signi¢cant di¡erences of mean values from baseline. Dunnett's t-test was used to determine the time at which treatment response differed from baseline. A value of p < 0.05 was considered signi¢cant.
Results Mares with bilateral perineal analgesia (BPA) The distance from the skin of the ¢rst coccygeal interspace to the needle point within the epidural space in 10 mares varied from 7.5 to 8.7 cm (8.5 0.5 cm, mean SD). Epidural administration of 0.5% ropivacaine (8 mL at the 5th sacral vertebrae and 9 mL at the sacrococcygeal vertebrae, respectively) resulted in varying degrees of bilateral analgesia, with dermatomal spread ranging from the coccyx to S4 and from the coccyx to S2 spinal cord segments in adult mares (Table 1). Tests of analgesia by needle prick indicated desensitized dermatomes supplied by the caudal, caudal rectal, perineal and pudendal nerves in all mares. In addition, analgesia of the caudal cutaneous femoral nerves on the right side was induced in one mare (143). This mare became ataxic. Mares responded with avoidance to 2.7 0.5 milliamps (mean SD) at the perineal area before epidural injection. Analgesia to electrical stimulation (> 40 milliamps) at the perineal area was achieved in 5^ 15 minutes (10 4 minutes, mean SD) and lasted 150^260 (196 42 minutes, mean SD) after injection in all mares (Table 1). Lack of avoidance response to maximal electrical stimulation (mean 66.6 16.1 milliamps) at the perineal area was achieved at 15^45 (mean 26 16) minutes and lasted 105^240 (mean157 44) minutes after injection (Fig. 4). Perineal sweating was observed in analgesic zones in all mares. Overall mean scores of the mare's behavior ranged from 0 to 1, with a mean value of 0.8 0.2. Degree of head drop ranged from 0 (no change) to 1 (muzzle at cubital joint), with mean value of 0.13 0.11 in mares. Mean scores of ataxia ranged from 0 67
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Figure 4 Quantitative assessment of perineal analgesia in 10 mares after epidural administration of ropivacaine (0.5%, 8 mL per 500 kg, ~ [bilateral perineal analgesia]) and in ¢ve of these mares after faulty epidural administration of ropivacaine ( [inadequate perineal analgesia]). Data are expressed as mean SD, with 0 milliamps being no analgesia, 40 milliamps being the analgesia threshold and 80 milliamps being the greatest degree of analgesia. Signi¢cant (p < 0.001) di¡erence between groups.
(no change of pelvic limb position) to 1 (slight swaying), with an overall mean value of 0.07 0.06. Cardiovascular and respiratory data Epidural administration of ropivacaine (0.08 mg kg 1) signi¢cantly reduced RR by 51% (p < 0.001) but did not signi¢cantly change HR, ABP, rectal temperature, arterial PO2, PCO2, SO2, pH, standard HCO3^, standard BE, PCV, Hb and TS concentrations (p > 0.05) (Tables 2 and 3). Mares with inadequate perineal analgesia (IPA) Five mares developed IPAand no signi¢cant (p > 0.05) changes of sedation, ataxia, behavior and cardiovascular, and respiratory parameters after ropivacaine administration (Tables 2 and 3). Bilateral perineal analgesia was achieved in the mares after the second ropivacaine administration at least10 days later.
Discussion Results of this study demonstrate that epidural administration of 0.5% ropivacaine hydrochloride solution (8 mL 500 kg 1) is capable of inducing profound and selective sensory blockade of nociceptive and motor ¢bers in dermatomes ranging from coccygeal to the second sacral vertebra within 68
5^15 minutes, and lasting longer than 2.5 hours, with minimal sedation, ataxia, changes of behavior, and cardiopulmonary e¡ects, in conscious adult mares. The reason for ¢ve mares not to demonstrate bilateral perineal analgesia after the ¢rst epidural injection of ropivacaine is speculative. Some ropivacaine could have been administered into the epidural space, but not in su¤cient quantity to bathe the last 2^3 pairs of sacral nerves in the vertebral space to produce bilateral analgesia. Inadequate perineal analgesia can result from improper injection technique, use of solutions of diminished potency and inadequate dispersal of the anesthetic in the epidural space (Skarda 1982). Faulty needle placement such as inappropriate angulation of the needle at the injection site or deviation of the needle from the midline seem to be the most likely causes for poor analgesia of mares in this study, because another needle placement and injection of the same anesthetic (8 mL of 0.5% ropivacaine) did induce BPA on a separate occasion. Inappropriate angulation of the spinal needle at the injection site before injection can be assumed if it can be felt that the needle point has struck the dorsal aspect of the vertebral arch. Deviation of the needle from the midline can be recognized by looking at the caudal aspect of the needle hub and axis of the free needle shaft in relation to the median plane; it also can be felt if the point strikes the transverse process. Asymetric and incomplete analgesia in the mare after proper needle placement into the epidural space is not uncommon (Skarda 1987). It may occur in mares that have anatomic pecularities from previous injections. If such is the case, another injection technique using a longer needle inserted at a lesser angle at a more distant site may provide good results (Fig. 2). It is our clinical experience, however, that unilateral and inadequate analgesia is more probably achieved if the spinal needle has been inserted a considerable distance into the vertebral canal (the actual distance of the needle bevel to the spinal cord), allowing the needle tip to deviate from the midline, and if a small amount of local anesthetic has been given to bathe the nerve roots primarily on one side of the spinal column. A larger volume (> 9 mL) of local anesthetic would have increased the incidence of successful bilateral perineal analgesia, however, it also would have increased the degree of ataxia and/ or produced recumbency of mares. Indications for the use of caudal epidural analgesia include pain relief and control of rectal tenesmus associated with irritation of the perineum, anus, Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Table 2 Cardiovascular and respiratory values (mean SD) from mares after epidural administration of ropivacaine HCl solution Time (minutes) after epidural administration of ropivacaine Variable Heart rate (beats min 1) BPA IPA Systolic arterial pressure (mm Hg) BPA IPA Mean arterial pressure (mm Hg) BPA IPA Diastolic arterial pressure (mm Hg) BPA IPA Respiratory rate (breaths min 1) BPA IPA Rectal temperature (8C) BPA IPA
0
30
34 10 34 7
60
120
180
240
300
32 8 33 9
32 8 31 5
31 7 34 6
31 6 34 6
31 7 35 4
33 10 33 5
144 7 142 7
141 10 135 6
143 14 136 8
141 10 143 8
149 15 143 13
146 12 143 15
147 12 144 13
114 6 114 8
110 9 107 6
113 10 108 7
115 7 118 7
116 11 119 13
117 12 114 10
119 10 117 7
91 6 91 6
92 7 84 5
92 9 87 6
93 11 93 7
97 10 99 12
99 9 95 12
94 12 95 12
29 8 28 10
18 7 20 5
16 5 22 7
14 5 23 3
15 4 20 6
16 5 20 5
15 6 18 6
37.8 0.3 37.7 0.4
37.8 0.3 37.6 0.4
37.7 0.3 37.7 0.4
37.7 0.3 37.6 0.4
37.7 0.3 37.6 0.4
37.7 0.3 37.6 0.4
37.7 0.3 37.6 0.4
BPA bilateral perineal analgesia (n 10); IPA inadequate perineal analgesia (n 5). Significant ( p < 0.05) change from time 0 (baseline). Data for times 5,15, 45,75, 90,105,135,150,165, and 240 minutes are available on request from author.
rectum and vagina during di¤cult labor, correction of uterine torsion, fetotomy and various obstetrical manipulations and surgical procedures such as repairs of recto-vaginal ¢stula, prolapsed rectum, urethrostomy, or anal, perineal, vulvar and bladder procedures in standing horses (Skarda1996). Drugs routinely used for epidural administration in horses include the local anesthetics lidocaine and mepivacaine and the alpha2-adrenoceptor agonists xylazine and detomidine (Skarda & Muir, 1996a, b). These drugs are either too short acting (lidocaine, mepivacaine; 1^2 hours;) or produce ataxia and signi¢cant CNS and cardiovascular depression (xylazine, detomidine). They are all at high risk of producing postural instability, rear limb ataxia, recumbency and excitement in conscious horses. Ropivacaine may be superior to lidocaine and mepivacaine solution for extended surgery in the caudal area of standing mares because of its longer duration of local anesthetic action (2.5 versus 1.5 hours) and may be superior to xylazine and detomidine because it produced more rapid onset of perineal analgesia (10 versus 30 minutes) with less sedation, ataxia, and cardiovascular and respiratory depression. Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
The intrinsic vasoconstrictive property of ropivacaine is of particular interest because vasoconstriction leads to prolonged analgesia and might not require the concomitant use of epinephrine (Kopacz et al. 1989; Guinard et al. 1991; Hurley et al. 1991; Nakamura et al. 1993; Cederholm et al. 1992, 1994; Geradini et al.1995; Koinig et al.1999). Ropivacaine is a commonly used local anesthetic in humans. It produced comparable sensory and sympathetic blockade but produced less intense motor blockade of shorter duration when compared to bupivacaine (Brown et al. 1990; Kerkamp et al. 1990a, 1990b; Brockway et al. 1991; Morrison et al. 1994; Gri¤n & Reynolds 1995). In addition, studies in animals indicate signi¢cantly less central nervous system and cardiac toxicity and dysrhythmogenicity following epidural ropivacaine (Feldman & Covino 1988; Feldman et al.1989,1991,1996; Scott et al.1989; Reiz et al. 1989; Nancarrow et al. 1989; Moller & Covino 1990; Pitkanen et al. 1992; Santos et al. 1999) when compared with bupivacaine. The reason for ropivacaine to be less cardiotoxic and produce less motor block than bupivacaine is not clear, but may be attributable to its S-(^) enantiomer form and lower lipid solubility rather than 69
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Table 3 Arterial acid-base and blood gas values (mean SD) from mares after epidural administration of ropivacaine HCl solution
Variable 0 Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA Arterial BPA IPA
Time (minutes) after epidural administration of ropivacaine 30 60 120 180
240
300
pH 7.43 0.02 7.44 0.02 7.44 0.02 7.45 0.02 7.44 0.03 7.44 0.03 oxygen tension (mm Hg) 101.6 7.4 105.4 6.9 105.1 7.9 103.0 3.0 105.4 9.8 102.3 7.8 carbon dioxide tension (mm Hg) 41.1 3.2 40.0 4.2 40.7 2.5 39.9 3.8 40.0 5.5 39.0 5.7 standard bicarbonate (mEq L 1) 26.9 1.4 26.7 1.8 27.0 1.4 26.9 2.2 26.9 2.0 28.0 5.6 standard base excess (mEq L 1) 2.8 1.2 2.9 1.3 3.0 1.4 3.3 1.6 3.1 1.4 2.5 2.0 PCV (%) 35.9 4.0 33.6 3.7 34.3 3.2 35.6 3.0 36.2 4.9 34.0 4.5 total hemoglobin concentration (g dL 1) 11.8 2.3 11.5 2.6 11.4 2.2 12.3 0.7 12.6 2.7 12.6 2.6 oxyhemoglobin saturation (%) 99.7 0.4 100.0 0.4 99.7 0.7 99.8 0.2 99.8 0.5 99.7 0.7 total solids concentration (g dL 1) 6.3 0.5 6.4 0.3 6.3 0.5 5.8 0.3 6.0 0.2 5.9 0.4
7.45 0.02 7.45 0.01
7.44 0.02 7.46 0.02
7.45 0.02 7.44 0.01
7.45 0.03 7.44 0.01
105.8 11.8 104.5 5.0
98.5 9.1 103.9 8.2
103.2 11.2 100.9 5.0
99.9 12.5 100.0 10.5
38.5 4.2 36.1 4.2
40.0 4.0 38.7 2.4
39.9 3.7 38.4 5.4
39.6 3.7 38.8 3.8
26.6 2.3 24.8 3.0
26.6 2.9 27.0 1.7
26.7 2.1 26.6 3.1
27.0 2.4 26.2 2.2
3.1 1.8 2.4 1.5
3.3 1.7 3.4 1.5
2.9 1.8 3.0 2.3
3.3 2.1 2.6 1.6
34.6 3.5 37.5 6.7
32.6 4.9 37.0 2.8
32.5 3.9 35.2 1.7
33.3 3.2 36.4 3.4
12.0 1.3 12.4 3.3
10.7 0.9 12.7 1.2
10.6 1.1 10.5 3.5
11.1 1.6 12.0 2.2
99.8 0.5 99.6 0.6
99.5 0.8 99.7 0.5
99.9 0.6 99.8 0.9
98.5 0.7 99.8 0.6
6.3 0.5 5.9 0.4
6.3 0.6 6.1 0.3
6.2 0.5 5.8 0.3
6.3 0.6 6.1 0.2
BPA bilateral perineal analgesia (n 10); IPA inadequate perineal analgesia (n 5). Data for times 90,150, and 210 minutes are available on request from author.
potency of ropivacaine (Rosenberg et al.1986; DeJong 1995). While both stereo isomers of ropivacaine are similar in their local anesthetic e¡ects, the S-(^) form appears to be less cardiotoxic than its R-() counterpart and less cardiotoxic than equipotent doses of bupivacaine (Etches et al.1997; Santos et al.1999). Dose^response studies to evaluate the potency of epidural ropivacaine and bupivacaine in humans and animals have not been reported. Studies, comparing 0.2^1.0% ropivacaine to 0.2^0.5% bupivacaine describe equipotent analgesia between the local anesthetics (Cederholm et al. 1994; D'A ngelo & James 1999). One study, however, which used an updown sequential allocation study design to estimate the minimum local analgesic concentration (MLAC) or ED50 of ropivacaine and bupivacaine, suggested that epidural ropivacaine was 40% less potent than epidural bupivacaine in patients (Polley et al.1999). 70
Previous clinical studies of ropivacaine in humans have focused on epidural anesthesia and analgesia. These studies used doses of ropivacaine ranging from 100 to 200 mg in varying concentration (0.25, 0.5, 0.75, 1.0%) and produced sensory anesthesia of equally long duration to that produced by bupivacaine but with less profound motor block (Gri¤n & Reynolds 1995; Katz et al. 1990; Kerkamp et al. 1990a). Results of epidural administration of ropivacaine in 900 patients undergoing general surgery have indicated that doses of 100^200 mg of ropivacaine achieved sensory block to the level of T10 in10 (range 5^13) minutes and that the median duration of e¡ect at the T10 level was 4 (range 3^5) hours. Higher doses produced a more profound block with a greater duration of e¡ect (Brown et al. 1990; Alahuhta et al. 1995; Schug et al. 1996). Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir
Doses of 400 mg and 450 mg of ropivacaine were administered to healthy mares, in the study reported here in which no surgery was performed, producing perineal analgesia to percutaneous electrical nerve stimulation (mean,66.6 16.1 milliamps) within 15^ 45 (mean, 26.4 15.5) minutes, and analgesia lasted 3 (2.5^4) hours. Percutaneous electrical stimulation of the perineum and needle pricks at sacral dermatomes, respectively, in mares can only mimic the intensity of surgical incision, even though previous studies in humans have shown that transcutaneous electrical stimulation at 60 milliamps was equivalent to the intensity of stimulation caused by surgical incisions (Petersen-Felix et al.1993; Zbinden et al. 1994). Epidural administration of 0.5% ropivacaine for caesarean section did not compromise the uteroplacental and fetal circulation in healthy parturient women with uncomplicated pregnancies (Alahuhta et al.1995). The e¤cacy of ropivacaine and bupivacaine for producing lumbar epidural anesthesia in dogs has been compared (Feldman et al. 1988, 1996; Hurley et al.1991; Duke et al.1999, 2000).Various concentrations of ropivacaine (0.25, 0.5, 0.75, 1%) and bupivacaine (0.25, 0.5, 0.75%) using a constant 3-mL epidural volume of ropivacaine and bupivacaine were used. There were no signs of adverse reactions, irreversible block or other sequelae in any of the dogs. Solutions of 0.25% ropivacaine and 0.25% bupivacaine failed to induce complete loss of weight support (mean weight 18.7 1.4 kg) following epidural injection. Onset of motor blockade varied between 5 and 9 minutes, with the use of higher concentrations (> 0.25%), and was inversely related to dose. Duration of motor blockade ranged from 141 minutes (0.5% ropivacaine) to 258 minutes (0.75% bupivacaine). The similar onset times for both drugs are related to their similar pKa values (ropivacaine, 8.0; bupivacaine,8.1) and that theyare both weak bases. Epidural ropivacaine and bupivacaine at similar volumes of 0.5% and 0.75% had similar sensory blockade and cardiopulmonary e¡ects in dogs. The higher concentration of both drugs at 0.22 mL kg 1 appeared to contribute to greater success of block (> 80%) at dermatomes L5 to L7 compared to 67% success with the other groups (Duke et al.1999, 2000). Recently, the e¤cacy of caudal (Co1-Co2) epidural administration of 1% ropivacaine, 2% lidocaine, and combination of 1% ropivacaine and 2% lidocaine for producing perineal anesthesia in 6 mares (320 24 kg) has been compared (Luna et al. 2000). All Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
anesthetics were combined with adrenaline 1 : 200 000 and given at a volume of 0.018 mL kg 1. The times to onset of anesthesia as evaluated by lack of response to painful stimulation of the perineum and vulva using forceps after injection of ropivacaine, lidocaine, and the mixture of ropivacaine and lidocaine were 17 7,15 5, and 7 1 minutes and perineal anesthesia lasted 285 32, 163 27, and 202 34 minutes, respectively. Three mares became recumbent, two received lidocaine and one received the combination of ropivacaine and lidocaine.When comparing these results to our study, the increased duration of perineal anesthesia (285 32 versus 195 42 minutes) and high incidence of ataxia (4 2) using a visual analogue scale from zero (no ataxia) to 10 (recumbency) was probably attributable to the higher concentration (1% versus 0.5%), larger volume (0.018 versus 0.016 mL kg 1), and admixture of adrenaline 1 : 200 000 administered to mares of the referenced study (Luna et al. 2000). Results of this study indicate that injection of ropivacaine (0.5%, 8 mL 500 kg 1) into the caudal epidural space induces prolonged (>2.5 hours) perineal analgesia with minimal sedation, ataxia, and no circulatory and respiratory disturbances in conscious standing mares. The advantages of ropivacaine 0.5% warrant further investigation, particularly under surgical conditions.
Acknowledgements This study was supported in part by Equine Research Funds of the College of Veterinary Medicine,The Ohio State University, USA. Presented in part at the 24th Annual Meeting of the American College of VeterinaryAnesthesiologists, Dallas,Texas. The authors thank Dr Jean Powers for statistical analysis and Jennifer Gadawski, Cheri Edwards and Steve Schumacher for technical assistance.
References Albright GA (1979) Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51, 285^287. Ðkerman B, Hellberg IB,Trossvik C (1988) Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand 32,571^578. Alahuhta S, Ra«sa«nen J, Jouppila P et al. (1995) The e¡ects of epidural ropivacaine and bupivacaine for cesarean section on uteroplacental and fetal circulation. Anesthesiology 83, 23^32. 71
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Brockway MS, Bannister J, McClure JH et al. (1991) Comparison of extradural ropivacaine and bupivacaine. Br J Anaesth 66,31^37. Brodner G, Mertes N, Van Aken H et al. (1999) Epidural analgesia with local anesthetics after abdominal surgery: earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine. Anesth Analg 88,128^133. Brown DL, Carpenter RL,Thompson GE (1990) Comparison of 0.5% ropivacaine and 0.5% bupivacaine for epidural anesthesia in patients undergoing lower-extremity surgery. Anesthesiology 72,633^636. Cederholm I, Evers H, Lofstrom JB (1992) Skin blood £ow after intradermal injection of ropivacaine in various concentrations with and without epinephrine evaluated by Doppler £owmetry. Reg Anesth17,322^328. Cederholm I, Anskar S, Bengtsson M (1994) Sensory, motor, and sympathetic block during epidural analgesia with 0.5% and 0.75% ropivacaine with and without epinephrine. Reg Anesth19,18^33. Cohen S, Hronkova B, Croitoru M et al. (1999) What is the optimal concentration of ropivacaine for continuous epidural infusion for labor pain? Anesthesiology 90, A32(Abstract). D'A ngelo R, James RL (1999) Is ropivacaine less potent than bupivacaine? Anesthesiology 90,941^943. DeJong RH (1995) 1995 Gaston Labat Lecture. Ropivacaine. White knight or dark horse ? Reg Anesth 20, 474^481. Duke T, Caulkett NA, Ball SD et al. (1999) Comparative analgesic and cardiopulmonary e¡ects of epidural bupivacaine and ropivacaine in conscious dogs. Proceedings of the 24th Annual Meeting of the American College of VeterinaryAnesthesiologists, Dallas,Texas. p12. Duke T, Caulkett NA, Ball SD et al. (2000) Comparative analgesic and cardiopulmonary e¡ects of bupivacaine and ropivacaine in the epidural space of the conscious dog. Vet Anaesthesia Analgesia 27,13^21. Etches RC, Writer WDR, Ansley D et al. (1997) Continuous epidural ropivacaine 0.2% for analgesia after lower abdominal surgery. Anesth Analg 84,784^790. Feldman HS, Arthur GR, Covino BG (1989) Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesth Analg 69,794^801. Feldman HS, Arthur GR, Pitkanen M et al. (1991) Treatment of systemic toxicity after rapid intravenous injection of ropivacaine and bupivacaine in conscious dogs. Anesth Analg 73,373^384. Feldman HS, Covino BG (1988) Comparative motor-blocking e¡ects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg 67,1047^1052. Feldman HS, Dvoskin S, Arthur GR et al. (1996)Antinociceptive and motor-blocking e¤cacy of ropivacaine and bupivacaine after epidural administration in the dog. Reg Anesth 21,318^326.
72
Gautier P, De Kock M, Van Steenberge A et al. (1999) A double-blind comparison of 0.125% ropivacaine with sufentanil and 0.125% bupivacaine with sufentanil for epidural labor analgesia. Anesthesiology 90,772^778. Geradini G, Samuelson U, JernbeckJ et al. (1995) Comparison of vascular e¡ects of ropivacaine on isolated rings of human arteries. Acta Anaesthesiol Scand 39,765^768. Gri¤n RP, Reynolds F (1995) Extradural anaesthesia for caesarean section: a double-blind comparison of 0.5% ropivacaine with 0.5% bupivacaine. Br J Anaesth 74,512^516. Guinard JP, Carpenter RL, Owens BD et al. (1991) Comparison between ropivacaine and bupivacaine after subcutaneous injection in pigs: cutaneous blood £ow and surgical bleeding. Reg Anesth16, 268^271. Hartmannsgruber MWB, Silverman DG, Halaszynski TM et al. (1999) Comparison of ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in volunteers. Anesth Analg 89,727^731. Hurley RJ, Feldman HS, Latka C et al. (1991) The e¡ects of epinephrine on the anesthetic and hemodynamic properties of ropivacaine and bupivacaine after epidural administration in the dog. Reg Anesth16,303^308. Kampe S,Weigand C, Kaufmann J et al. (1999) Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement. Anesth Analg 89,395^398. Katz JA, Knarr D, Brindenbaugh PO (1990) A double-blind comparison of 0.5% bupivacaine and 0.75% ropivacaine administered epidurally in humans. Reg Anesth 15, 250^252. Kerkamp HE, Gielen MJ, EdstrÎm HH (1990a) Comparison of 0.75% ropivacaine with epinephrine and 0.75% bupivacaine with epinephrine in lumbar epidural anesthesia. Reg Anesth15, 204^207. Kerkamp HE, Gielen MJ, Wattwil M et al. (1990b) An open study comparison of 0.5%, 0.75% and 1.0% ropivacaine, with epinephrine, in epidural anesthesia in patients undergoing urologic surgery. Reg Anesth15,53^58. Klein SM, Greengrass RA, Steele SM et al. (1998) A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block. Anesth Analg 87,1316^1319. Knudsen K, SuurkÏla MBB, Blomberg S et al. (1997) Central nervous and cardiovascular e¡ects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 78,507^514. Koinig H, Krenn CG, Glaser C et al. (1999) The dose^response of caudal ropivacaine in children. Anesthesiology 90, 1339^1344. Kopacz DJ, Carpenter RL, Mackey DC (1989) E¡ect of ropivacaine on cutaneous capillary blood £ow in pigs. Anesthesiology 71,69^74. Liu SS, Moore JM, Luo AM et al. (1999) Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia. Anesthesiology 90,727^733.
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir Luna SPL, Bueno SK, Cruz ML et al. (2000) Extradural anaesthesia using lidocaine, ropivacaine, hyperbaric lidocaine and a combination of lidocaine and ropivacaine in mares.Vet Anaesthesia Analgesia 27,57(Abstract). Moller R, Covino BG (1990) Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic.Anesthesiology 72,322^329. Morrison LM, Emanuelsson BM, McClure JH et al. (1994) E¤cacy and kinetics of extradural ropivacaine: a comparison with bupivacaine. Br J Anaesth 72,164^169. Nakamura K,Toda H, Kakuyama M, et al. (1993) Direct vascular e¡ects of ropivacaine in femoral artery and vein of the dog. Acta Anaesthesiol Scand 37, 269^273. Nancarrow C, Rutten AJ, RuncimanWB et al. (1989) Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg 69, 276^283. Owen MD, D'A ngelo R, Gerancher JC et al. (1998) 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled epidural infusion. Anesth Analg 86,527^531. Petersen-Felix S, Zbinden AM, Fischer M et al. (1993) Iso£urane minimum alveolar concentration decreases during anesthesia and surgery. Anesthesiology 79,959^965. Pitkanen M, Feldman HS, Arthur GR et al. (1992) Chronotropic and inotropic e¡ects of ropivacaine, bupivacaine, and lidocaine in the spontaneously beating and electrically paced isolated, perfused rabbit heart. Reg Anesth 17,183^192. Polley LS, Columb MO, Naughton NN et al. (1999) Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor. Anesthesiology 90, 944^950. Reiz S, Ha«ggamark S, Johansson G et al. (1989) Cardiotoxicity of ropivacaine ^ a new amide local anaesthetic agent. Acta Anaesthesiol Scand 33,93^98. Rosenberg PH, Kytta« A, Alila A (1986) Absorption of bupivacaine, etidocaine, lidocaine and ropivacaine into nheptane, rat sciatic nerve, and human extradural and subcutaneous fat. Br J Anaesth 58,310^314. Santos AC, Karpel B, Noble G (1999) The placental transfer and fetal e¡ects of levobupivacaine, racemic bupivacaine, and ropivacaine. Anesthesiology 90,1698^1703. Santos AC, Arthur GR, Wlody D et al. (1995) Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes. Anesthesiology 82, 734^740. Schug SA, Scott DA, Payne J et al. (1996) Postoperative analgesia by continuous extradural infusion of ropivacaine after upper abdominal surgery. Br J Anaesth 76, 487^491. Scott DA, Blake D, Buckland M et al. (1999) A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 mg/mL fentanyl for seventy-two hours of
Veterinary Anaesthesia and Analgesia, 2001, 28, 61^74
postoperative analgesia after major abdominal surgery. Anesth Analg 88,857^864. Scott DA, Chamley DM, Mooney PH et al. (1995) Epidural ropivacaine infusion for postoperative analgesia after major lower abdominal surgery ^ a dose ¢nding study. Anesth Analg 81,982^986. Scott DB, Lee A, Fagan D et al. (1989) Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 69,563^569. Scrutton MJ, Srikantharajah I,Williams H et al. (1998) Comparison of ropivacaine with bupivacaine for epidural analgesia in labor. Anesth Analg 81, A34(Abstract). Skarda RT (1982) Practical regional anesthesia. In. Equine Medicine and Surgery (3rd edn). Mansmann RA, McAllister ES, Pratt PW (eds). AmericanVeterinary Publications, Santa Barbara, CA, pp. 228^249. Skarda RT (1987) Local and regional analgesia. In: Principles and Practice of Veterinary Anesthesia. Short CE (ed. ).Williams & Wilkins, Baltimore, MD, pp.91^133. Skarda RT (1996) Local and Regional Analgesic Techniques. B. Horses. In: Lumb and Jones' Veterinary Anesthesia. Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins, Baltimore, MD, pp. 448^478. Skarda RT, MuirWW (1983) Continuous caudal epidural and subarachnoid anesthesia in mares: a comparative study. Am J Vet Res 44, 2290^2298. Skarda RT, MuirWW (1996a) Analgesic, hemodynamic, and respiratory e¡ects of caudal epidurallyadministered xylazine hydrochloride solution in mares. Am J Vet Res 57, 193^200. Skarda RT, Muir WW (1996b) Comparison of antinociceptive, cardiovascular, and respiratory e¡ects, head ptosis, and position of pelvic limbs in mares after caudal epidural administration of xylazine and detomidine hydrochloride solution. Am J Vet Res 57,1338^1345. Skarda RT, Muir WW (1999) Analgesic, hemodynamic and respiratory e¡ects of caudal epidurally administered ropivacaine hydrochloride solution in mares. Proceedings of the 24th Annual Meeting of the American College of VeterinaryAnesthesiologists, Dallas,Texas.p.14. Tuttle AA, Katz JA, Brindenbaugh PO et al. (1995) A doubleblind comparison of the abdominal wall relaxation produced by epidural 0.75% ropivacaine and 0.75% bupivacaine in gynecologic surgery. Reg Anesth 20, 515^520. Vallejo M, Mandell G, Makishima S et al. (1999a) Walking epidural ropivacaine analgesia during labor. Anesthesiology 90, A37(Abstract). Vallejo M, Mandell G, Makishima S et al. (1999b) E¤cacy of 0.05% ropivacaine for walking labor epidural analgesia. Anesthesiology 90, A38(Abstract). Wicks TC (1995) Ropivacaine: an introduction to a new local anesthetic. CRNA 6,129^134. Zaric D, Nydahl PA, Philipson L et al. (1996) The e¡ect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25% bupivacaine on sensory and
73
E¡ects of caudal epidurally administered ropivacaine hydrochloride solution RT Skarda & WW Muir motor block in volunteers: a double-blind study. Reg Anesth 21,14^25. Zbinden AM, Maggiorini M, Petersen-Felix S et al. (1994) Anesthetic depth de¢ned using multiple noxious stimuli during iso£urane/oxygen anesthesia: I. Motor reactions. Anesthesiology 80, 253^260.
74
Zwack R, Campbell DC, Sawatzky K et al. (1999) Ambulatory labor epidural analgesia: bupivacaine versus ropivacaine. Anesthesiology 81, A899 (poster).
Received 22 December1999, Accepted1 March 2000.
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