Comparison of lidocaine, lidocaine/epinephrine or bupivacaine for thoracolumbar paravertebral anaesthesia in fat-tailed sheep
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1 Veterinary Anaesthesia and Analgesia, 2011, 38, doi: /j x SHORT COMMUNICATION Comparison of lidocaine, lidocaine/epinephrine or bupivacaine for thoracolumbar paravertebral anaesthesia in fat-tailed sheep Maryam Rostami & Nasser Vesal Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran Correspondence: Nasser Vesal, Department of Veterinary Clinical Sciences, School ofveterinary Medicine, Shiraz University, Shiraz, Iran. Abstract Objective To evaluate the speed of onset and duration of loss of sensation in the flank following paravertebral administration of lidocaine (with or without epinephrine) or bupivacaine. Study design Blinded, randomized experimental study. Animals Nine healthy fat-tailed male lambs (mean weight ± SD, 22.9 ± 3 kg). Each animal was used twice. Methods Animals were allocated randomly to receive two of three treatments: lidocaine 2% (LID, n = 6), lidocaine with epinephrine 5 lg ml )1 (LIDEP, n = 6) or bupivacaine 0.5% (BUP, n = 6). The sheep received a total volume of 9 ml (3 ml for each paravertebral nerve) of anaesthetic. Onset and duration of loss of sensation on the flank were evaluated using nociceptive stimuli (superficial and deep pin-prick and clamping with a haemostat). Values for heart (HR) and respiratory (f R ) rates, rectal and skin temperatures were recorded before and at predetermined intervals after paravertebral injection. Parameters were compared using ANOVA followed by Duncan s test where relevant. Results Mean ± SD times to onset of loss of flank sensation following paravertebral administration of LID, LIDEP or BUP were 1.8 ± 1.2, 2.0 ± 0.9 and 3.6 ± 1.3 minutes, respectively. Durations of action in minutes were 65 ± 18, 95 ± 46 and 303 ± 98, respectively. Onset and duration of effects after BUP treatment were significantly longer than after LID or LIDEP (p < 0.05), but did not differ significantly between LID and LIDEP. No clinical signs of local anaesthetic toxicity were noticed and HR and f R remained stable with all protocols. Conclusions and clinical relevance Paravertebral administration of bupivacaine produces a longer duration of anaesthesia when compared to lidocaine with or without epinephrine and is indicated when prolonged flank surgery is to be performed. Keywords bupivacaine, epinephrine, lidocaine, paravertebral, sheep. Introduction In ruminants, surgical procedures often are performed under local or regional anaesthesia in animals in the standing position and without sedation. Thoracolumbar paravertebral block (TLPVB) is used commonly for flank laparotomy, and generally is considered preferable to infiltration anaesthesia such as line block or inverted L block, because of the lower amounts of the anaesthetic solution used, more complete analgesia of the abdominal wall and minimized oedema and haematoma formation. Regional anaesthesia of the dorsal and ventral branches of the thirteenth thoracic (T13) and the 598
2 first and second lumbar (L1 and L2) nerves is the basis of the paravertebral block to provide anaesthesia of the flank region for abdominal surgery (Skarda & Tranquilli 2007b). Most commonly, lidocaine, with or without the addition of epinephrine, is the local anaesthetic agent used for the purpose. Bupivacaine is a long-acting amino-amide local anaesthetic agent, which has been used for epidural (Trim 1989), intra-articular (Shafford et al. 2001) and brachial plexus nerve block (Estebe et al. 2000) in ruminants. The doses of 1 2 mg kg )1 of bupivacaine have been recommended for infiltration anaesthesia in ruminants (Hellyer et al. 2007). To the authors knowledge, there are no published studies evaluating the anaesthetic effect of paravertebral administration of bupivacaine in ruminants. There is also limited information available on the effects of addition of epinephrine on onset and duration of lidocaine anaesthesia. The objective of this study reported here was to evaluate the speed of onset and the duration of loss of sensation following paravertebral administration in sheep using lidocaine (LID), lidocaine/epinephrine (LIPEP) or bupivacaine (BUP). Materials and methods The Institutional Animal Care and Use Committee approved the protocol for this project. Nine healthy, fat-tailed Mehraban male lambs, aged (mean ± SD) 3.6 ± 0.4, range months and weight 22.9 ± 3 kg, were used in the present study. Each sheep was used twice and the procedure was performed only on the right flank. The sheep were allowed an acclimatization period of 2 weeks prior to the beginning of the study. Health status was established on the basis of a thorough physical examination and normal complete blood count and total protein. Sheep were assigned randomly to two of three treatments (six sheep per treatment). Treatment LID received 2% lidocaine hydrochloride (Caspian Tamin Pharmaceutical Co., Iran) by paravertebral injection; treatment LIDEP, 2% lidocaine hydrochloride with 5 lg ml )1 epinephrine (Darou Pakhsh Co, Iran) and treatment BUP, 0.5% bupivacaine hydrochloride (0.5%; Merk Company, France). An interval of at least 7 days was allowed between re-use in another treatment. Lidocaine-epinephrine solution was freshly prepared by adding epinephrine (1:1000) from an individual sealed ampoule to 2% lidocaine immediately before use. The ph of the anaesthetic solutions was determined using a laboratory ph meter (Crison ph meter; Basic 20 +, Spain). Animals were fasted for 12 hours before experiments, but water was available at all times. Skin overlying the last thoracic, L1, L2 and L3 transverse process and flank area was clipped and prepared aseptically. After locating the L1 transverse process, a 23-gauge, 8.9 cm spinal needle (KOSAN Corporation, Japan) was inserted cm lateral to the dorsal midline until its point encountered the transverse process. The needle was then, walked off the cranial edge of the transverse process and advanced approximately 1 cm to pass through the intertransverse ligament. Two ml of local anaesthetic solution was injected to desensitize the ventral branch of T13. The needle was withdrawn approximately 1 cm dorsal to the surface of the transverse process and an additional 1 ml of the anaesthetic was injected to desensitize the dorsal branch of T13. The first and second lumbar nerves were blocked in the same manner. The anaesthetic solution consisted of 3 ml of LID, LIDEP or BUP for each nerve block; therefore, all sheep received a fixed total volume of 9 ml of anaesthetic solution. The distance from the skin to the transverse process and the depth of needle insertion before injection were determined by measuring the length of the needle (distance between the needle hub and tip of the needle) and subtracting the distance between the skin and needle hub. Time to onset and duration of complete antinociception in the midflank area were recorded based on the complete absence of response to nociceptive stimuli. The stimuli were superficial and deep pin prick with a 25-gauge needle and pinching of skin with a haemostat closed to the first ratchet. The area tested was that of a proposed incision line for flank laparotomy, 3 4 cm caudal and parallel to the last rib and close to the middle of the paralumbar fossa. In order to determine the time to onset, nociceptive testing was performed every 30 seconds after the completion of the third paravertebral injection until the animal showed no response. After this time, loss of sensation was evaluated every 10 minutes until a response was observed. The same investigator assessed local anaesthesia in all cases, and was unaware of the treatment given. Heart rate (HR) was measured by counting the heart beats over the cardiac area using a stethoscope. Respiratory rate (f R ) was measured by counting chest movements. Rectal temperature Ó 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38,
3 was measured with a digital thermometer. Skin temperature was recorded in the midflank region using an infrared thermometer (Riester; GmbH & Co., Jungingen, Germany). Heart rate, f R, and rectal and skin temperatures were measured before paravertebral drug administration and 5, 10, 15, 20, 30, 40, 50, 60, 75 minutes after drug injection and every 15 minutes until the end of local anaesthesia. Statistical analysis All data are presented as mean ± SD for each treatment treatment. Data were distributed normally (Kolgomorov Smirnov test). Heart rate, f R, and rectal and skin temperature values were compared by analysis of variance (ANOVA) for repeated-measures with time and treatment as factors, followed by Duncan s test. A one-way ANOVA followed by Duncan s test was used to compare onset and duration of anaesthesia. Statistical analysis was undertaken using SPSS Version 10 for Windows (SPSS, MicroMaster, PA, USA) and p 0.05 was considered significant. Table 1 Body weight, distance from the skin to the transverse process, distance from the skin to the injection site, dose administered, time to onset of anaesthesia and duration of anaesthesia in sheep (n = 6) receiving paravertebral bupivacaine, lidocaine or lidocaine-epinephrine. Results are mean ± SD (range). Treatments Bupivacaine Lidocaine Lidocaine epinephrine Body weight (kg) 22 ± 4 23 ± 3 24 ± 3 Distance from skin to transverse process (cm) 2.7 ± ± ± 0.3 Distance from skin to injection site (cm) 3.6 ± ± ± 0.5 Dose administered in mg kg )1 (range) 2.1 ± ± ± 1.1 ( ) ( ) ( ) Time to onset of anaesthesia in minutes (range) 3.6 ± 1.3* 1.8 ± ± 0.9 ( ) ( ) ( ) Duration of anaesthesia in minutes (range) 303 ± 98* 65 ± ± 46 ( ) (44 85) (41 151) *Significant differences from other treatments (p < 0.05). Results There were no significant differences in body weight, the mean distance from skin to transverse process or the mean distance from skin to injection site between treatments (Table 1). The correct site for injection of local anaesthetic was located easily and the procedure was completed within 5 minutes. The anaesthetic doses of BUP, LID and LIDEP for each treatment were 2.1 ± 0.4 mg kg )1, 8.0 ± 1.1 mg kg )1 and 7.7 ± 1.1 mg kg )1, respectively. The ph of LID, LIDEP and BUP was 6.28, 6.27 and 5.56, respectively. A significant difference was not detected in the time to onset or duration of loss of sensation between LID and LIDEP, but onset for both treatments was significantly faster (p < 0.05) than that for BUP (Table 1). Duration of anaesthesia was significantly longer (p < 0.05) in BUP treatment compared to the other treatments. No change in HR, f R and skin temperature (data not shown) were observed in any treatment. In all treatments, a mean increase of 0.2 C was observed in flank skin temperature 35 minutes after paravertebral injection (Table 1). No adverse reactions associated with paravertebral administration of drugs or obvious signs of local anaesthetic toxicity were observed. Discussion Local anaesthetics have the unique ability to block completely the sensation of pain and have been used clinically as the sole analgesic for surgery, and also as adjuncts to general anaesthesia in small and large animals (Skarda & Tranquilli 2007a). They decrease general anaesthetic requirement, improve the quality of recovery and prevent central sensitization of nociceptive pathways after painful surgical procedures, reducing the requirements for postoperative analgesia (Hubbell 2007). Local and regional anaesthetic techniques also may be used before, during, or after surgery to provide postoperative analgesia. In this study, unilateral paravertebral blockade did not change HR, f R or rectal temperature in conscious sheep. When compared with lumbosacral epidural anaesthesia, paravertebral block offers the advantages of providing complete flank anaesthesia without producing hypotension, respiratory depression, hypothermia and hindlimb paralysis (Skarda & Tranquilli 2007b). When compared with line or inverted L block, a smaller quantity of local anaesthetic agent is required, and so the risk of systemic local anaesthetic toxicity may be reduced. 600 Ó 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38,
4 Behavioural responses to painful stimuli are difficult to assess in sheep due to their stoic nature. A simple anti-nociceptive scoring system was chosen because, in most cases, muscle twitch of the flank region was the only reliable response observed during noxious stimulation. The addition of epinephrine to lidocaine is anticipated to delay the onset of action both by decreasing the ph of anaesthetic solution, thus reducing the amount of non-ionized local anaesthetic (Skarda & Tranquilli 2007a), and by producing vasoconstriction, reducing spread to the site of action. In the present study, the addition of epinephrine (5 lg ml )1 ) to lidocaine only changed the ph from 6.28 to 6.27, and there was no significant difference, with respect to onset of sensory blockade between plain lidocaine and lidocaine containing epinephrine. It should be mentioned that the ph of freshly prepared lidocaine-epinephrine solution was higher than the ph of a commercially available preparation (Nasr; Pharmaceutical Co., Fariman, Iran) containing epinephrine (6.27 compared to 4.24). Although the onset of anaesthesia with bupivacaine took significantly longer than that of lidocaine the difference is irrelevant clinically. Paravertebral administration of LID and LIDEP induced comparable loss of sensation of the flank. It had been anticipated that lidocaine containing epinephrine would result in more prolonged anaesthesia because of the local vasoconstrictive effect of epinephrine. The lack of a significant difference between lidocaine and lidocaine-epinephrine treatments may have been attributed to the relatively small sample size of each treatment or a low concentration of epinephrine used with lidocaine in this study. Epinephrine is said to be effective when added to anaesthetic solution in concentration of 5 20 lg ml )1 (Skarda & Tranquilli 2007a), but the optimal concentration of epinephrine for paravertebral anaesthesia is not known. The lowest recommended concentration of epinephrine was used in the present study. Following paravertebral administration of bupivacaine, anaesthesia of the flank can be expected to persist for at least 2.5 and up to 7 hours, which provides an extended duration of surgical anaesthesia and pain management in the early post-laparotomy period. Although the complications associated with TLPVB usually are rare, the possible toxic effects of systemic absorption of local anaesthetics should be considered. The mean doses of IV lidocaine required for central nervous system and cardiovascular toxicity in sheep are 5.8 and 36.7 mg kg )1, respectively (Morishima et al. 1981). In awake sheep, the mean fatal doses of IV bupivacaine and lidocaine have been quoted as 3.7 and 30.8 mg kg )1, respectively, indicating a fatal dose ratio of about 1:8.3 (Nancarrow et al. 1989). Blood levels of local anaesthetics are lower following systemic absorption after TLPVB compared to those occurring when the same doses are given IV, and therefore with TLPVB higher doses are required before toxic effects are likely to be seen. Administration of plain lidocaine at a dose of 20 mg kg )1, but not 10 mg kg )1, for inverted L block resulted in CNS toxicity without fatality in pregnant sheep (Scarratt & Troutt 1986). Studies of the pharmacokinetics of lidocaine and bupivacaine and the effects of epinephrine addition on plasma concentration of local anaesthetics could provide useful information on systemic toxicity following paravertebral administration of local anaesthetics in sheep. In sheep and goats, 2 5 ml of a 1 2% lidocaine (Skarda & Tranquilli 2007b) has been recommended for blocking the ventral and dorsal nerve roots at each site. In the present study in lambs, the total volume injected was 9 ml (3 ml for each nerve) in all animals regardless of body weight, therefore, the maximum dose given to an individual lamb of LID, LIDEP or BUP was 10.1, 9.2 and 2.8 mg kg )1, respectively. These doses are lower than the toxic doses of lidocaine and bupivacaine in sheep. Larger sheep may receive 5 6 ml per site for more complete coverage but care must be taken not to exceed the safe doses. Paravertebral anaesthesia increases skin temperature of the flank region in cattle, which is attributable to vasodilation and increased skin blood flow resulting from sympathetic nerve block (Skarda & Tranquilli 2007b). In the present study, no significant changes were detected in skin temperature following paravertebral administration of anaesthetics. Possibly the thermometer was not sensitive enough to detect changes in skin temperature. However, we have successfully used the same instrument to detect a rise in skin temperature following paravertebral anaesthesia in cattle. Alternatively, cutaneous vascular beds may be less sensitive to sympathetic blockade in the flank region of sheep, or at least of these young lambs, than in the cattle. In conclusion, in this study, when used for paravertebral anaesthesia, the addition of epineph- Ó 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38,
5 rine to lidocaine did not significantly influence either the onset or the duration of loss of sensation in the flank region. Onset of loss of sensation when bupivicaine was used was statistically, but not clinically, significantly slower after bupivicaine than after lidocaine but it provided a more prolonged effect. Thus bupivicaine is useful for prolonged surgery and may contribute to a longer pain relief in the immediate postoperative period in sheep undergoing flank abdominal surgery. Acknowledgements This work was supported by grant No. 88-GR-VT- 29 from the Research Council of Shiraz University. References Estebe JP, Corre P, Chevanne F et al. (2000) Motor blockade by brachial plexus block in the sheep. Anesthesiology 93, Hellyer PW, Robertson SA, Fails AD (2007) Pain and its management. In: Lumb & Jones Veterinary Anesthesia and Analgesia (4th edn). Tranquilli WJ, Thurmon JC, Grimm KA (eds). Blackwell Publishing, IA, USA. pp Hubbell JAE (2007) Anesthesia, analgesia and immobilization of selected species and classes of animals: horses. In: Lumb & Jones Veterinary Anesthesia and Analgesia (4th edn). Tranquilli WJ, Thurmon JC, Grimm KA (eds). Blackwell Publishing, IA, USA. pp Morishima HO, Pedersen H, Finster M et al. (1981) Toxicity of lidocaine in adult, newborn, and fetal sheep. Anesthesiology 55, Nancarrow C, Rutten AJ, Runciman WB 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, Scarratt WK, Troutt HF (1986) Iatrogenic lidocaine toxicosis in ewes. J Am Vet Med Assoc 188, Shafford HL, Mallinckrodt CH, Turner AS et al. (2001) Intraarticular lidocaine and bupivacaine in sheep undergoing stifle arthrotomy. Vet Anaesth Analg 28, Skarda RT, Tranquilli WJ (2007a) Local anesthetics. In: Lumb & Jones Veterinary Anesthesia and Analgesia (4th edn). Tranquilli WJ, Thurmon JC, Grimm KA (eds). Blackwell Publishing, IA, USA. pp Skarda RT, Tranquilli WJ (2007b) Local and regional anesthetic and analgesic techniques: ruminant and swine. In: Lumb & Jones Veterinary Anesthesia and Analgesia (4th edn). Tranquilli WJ, Thurmon JC, Grimm KA (eds). Blackwell Publishing, IA, USA. pp Trim CM (1989) Epidural analgesia with 0.75% bupivacaine for laparotomy in goats. J Am Vet Med Assoc 194, Received 9 February 2011; accepted 25 March Ó 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38,
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