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Sciatic-femoral nerve block with bupivacaine in goats undergoing elective stifle arthrotomy
The Veterinary Journal 188 (2011) 53–57
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The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Sciatic-femoral nerve block with bupivacaine in goats undergoing elective stifle arthrotomy q Chiara Adami a,*, Alessandra Bergadano a, Rupert M. Bruckmaier b, Michael H. Stoffel b, Marcus G. Doherr b, Claudia Spadavecchia a a b
Department of Clinical Veterinary Medicine, Anaesthesiology Division, Vetsuisse-Faculty, University of Berne, 3012 Berne, Switzerland Department of Clinical Research and Veterinary Public Health, Vetsuisse-Faculty, University of Berne, 3012 Berne, Switzerland
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Article history: Accepted 14 February 2010
Keywords: Analgesia Bupivacaine Sciatic-femoral nerve block Loco-regional anaesthesia Goat
a b s t r a c t The aim of this study was to describe the sciatic-femoral nerve block (SFNB) in goats and to evaluate the peri-operative analgesia when the goats underwent stifle arthrotomy. The animals were randomly assigned to one of four treatment groups: groups 0.25, 0.5 and 0.75 received 0.25%, 0.5% and 0.75% of bupivacaine, respectively, while group C (control group) received 0.9% NaCl. In all groups, the volume administered was 0.2 mL/kg. Intra-operatively, the proportion of animals receiving rescue propofol was significantly lower in groups 0.5 and 0.75, compared to group C. Post-operatively, the visual analogue scale (VAS) and total pain score were significantly higher in group C than in the other groups. Group 0.75 had the highest percentage of animals showing motor blockade. SFNB performed with bupivacaine resulted in better intra- and post-operative analgesia than SFNB performed with saline. Compared to the other concentrations, 0.5% bupivacaine resulted in satisfactory analgesia with acceptable side effects. Ó 2010 Elsevier Ltd. All rights reserved.
Introduction Pain assessment in ruminants has received less attention than in small animals as they rarely show classical signs of pain, such as vocalisation, restlessness or violent motor activity (Valverde and Gunkel, 2005). Due to anatomical similarities with the human stifle joint, small ruminants are becoming an increasingly common model for comparative orthopaedic research (Dowd et al., 1998). As these experimental procedures are invasive and painful, aggressive pain management in the intra-operative and early post-operative period is essential. The use of local and regional anaesthesia techniques has increased over the past decade as a key component of balanced analgesia in humans and small animals (Cox and Riedesel, 1997; Ramussen et al., 2006). The main advantages of using loco-regional anaesthesia as part of a balanced anaesthesia protocol are better analgesia (via blockage of peripheral pain pathways) and a decrease in the amount of opioids and inhalation anaesthetics needed to maintain anaesthesia, resulting in less associated side effects. Few techniques have been specifically described for small ruminants. Intra-articular injection of local anaesthetic drugs has been
q Part of the preliminary results of this study was presented at the AVA congress in Barcelona in October 2008. * Corresponding author. Tel.: +41 031 631 2791; fax: +41 031 631 2620. E-mail address: [email protected] (C. Adami).
1090-0233/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2010.02.008
reported to reduce post-operative pain in sheep undergoing stifle arthrotomy (Shafford et al., 2004). However, the technique is contraindicated if the experimental procedures aim to evaluate chondral regeneration due to the potential interaction of the local anaesthetic with the cartilage healing process (Bailie and Ellenbecker, 2009). Several studies have evaluated the efficacy of epidural anaesthesia in both sheep and goats (Aithal et al., 1996a,b; Mpanduji et al., 1999). The administration of analgesics and local anaesthetics into the epidural space is common practice in veterinary medicine and although it is effective in providing peri-operative analgesia for hindlimb surgeries, potential side effects and complications should be taken into account. For example, bilateral motor blockade often occurs with epidural anaesthesia but is undesired in ruminants as it may lead to discomfort and distress (Mpanduji et al., 1999). Moreover, as the caudal extension of the spinal cord can vary among individuals, the possibility of damaging the cauda equina when placing the needle in the lumbosacral epidural space may increase the risk of iatrogenic complications (Mpanduji et al., 2000). To our knowledge, there are no reports on the use of sciaticfemoral nerve block (SFNB) in goats. We hypothesised that in goats undergoing surgery involving the stifle joint the SFNB may be an effective, technically easy, inexpensive alternative to other previously described techniques. The aims of this study were therefore to describe the SFNB technique and to evaluate its peri-operative efficacy in goats undergoing stifle arthrotomy.
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C. Adami et al. / The Veterinary Journal 188 (2011) 53–57
Fig. 1. Experimental time table. C: blood sampling for cortisol serum measurement at the following time points: baseline ( 20 min), after incision (0), and 60 (60 min) and 120 (120 min) minutes after skin incision; A: beginning of general anaesthesia; SFNB: sciatic-femoral nerve block; S: surgery; a: VAS; b: total pain score; c: reaction to palpation (wound and joint); d: evaluation of presence or absence of motor blockade.
The study was designed as a prospective, block randomised, blinded, placebo controlled experimental trial.
Animals were randomly assigned to four treatment groups, each including 13 animals, as follows: goats of group 0.25 received bupivacaine 0.25% (Carbostesin 0.25%, AstraZeneca); goats of groups 0.5 and 0.75 received bupivacaine 0.5% and 0.75% (Carbostesin 0.5%, AstraZeneca; Bupivacaine 0.75%, Sintetica), respectively. Group C was used as the controls and received 0.9% NaCl. SFNBs were always performed by the same anaesthetist (C.A.), blinded to the treatment.
Animals
Surgery
Fifty-two Saanen goats, females, 2 years old, weighing 60 ± 3.2 kg, were used in this study. A thorough examination of each animal was performed on arrival to assess the health status. Exclusion criteria were pregnancy, sickness, abnormal posture or lameness, and intra-operative findings of cartilage defect. Prior to surgery, no food was provided for 24 h and access to water was restricted for 12 h. The experimental trial was performed with permission from the local committee for animal experimentation (Canton of Berne, Switzerland).
All goats underwent knee arthrotomy followed by the creation of three osteochondral defects (6 mm diameter, 0.8 mm depth), in the trochlea and in each condyle, respectively.
Materials and methods Study design
Anaesthesia A 14 G (80 mm) catheter was aseptically placed in the jugular vein for intravenous (IV) drug administration and blood sampling. Following pre-medication with IV midazolam (0.3 mg/kg, Dormicum, Roche) and IV methadone (0.05 mg/kg, Methadon, Streuli), anaesthesia was induced with IV ketamine (3 mg/kg, Narkan 100, Dr. E. Gräub) and propofol (1 mg/kg, Propofol, Fresenius). After endotracheal intubation, performed under laryngoscopic visualisation, anaesthesia was maintained with sevoflurane (Sevoflurane, Abbott) in air/oxygen (1:1) administered through a circle system. A constant end-tidal sevoflurane concentration (PE’Sevo) of 2.9%, equivalent to 1.25 the minimum alveolar concentration (MAC) (Steffey and Mama, 2007) was targeted during anaesthesia. Goats were instrumented with an electrocardiogram and an end-tidal gas analyser (Anandic Medical System, Datex-Ohmeda). The caudal auricular artery was cannulated for arterial blood pressure monitoring. Heart rate (HR), systolic arterial blood pressure (SAP), mean arterial blood pressure (MAP), diastolic blood pressure (DAP), respiratory rate (fr), end-tidal carbon dioxide tension (PE CO2), and PE’Sevo data were electronically recorded every 5 s on a computer from the beginning of general anaesthesia until the end of the surgical procedure. During the procedure animals received IV ringer lactate solution (5 mL/kg/h, Ringer Lactate, Bischel). If MAP fell <70 mm Hg, dopamine was infused at 5 lg/kg/min. Flunixin meglumine (1.1 mg/kg, Finadyne, Biokema) was administered IV at the end of the procedure, then intramuscularly (IM) once a day for the 4 days following. Nerve block The sciatic and femoral nerves were located using a nerve stimulator (TOF watch, Organon), according to techniques previously described in dogs (Campoy, 2008; Clark, 2008; Mahler, 2008; Mahler and Adogwa, 2008). For sciatic nerve location, the animals were placed in lateral recumbency with the (randomly assigned) operative leg uppermost (Fig. 2). The anatomical landmarks of the greater trochanter and the ischiatic tuberosity identified by palpation; a mark was then made at each point and a line was drawn between them. After aseptic preparation of the skin, a small incision was made with a needle at one-third of the distance from the great trochanter. The stimulating needle was then inserted through the incision at a 60° angle toward the great trochanter. Electrical stimulation was given at 1 Hz, starting at an intensity of 2.0 mA. Contractions of the biceps femoris, semitendinosus and semimembranosus muscles (with consequent extension of the hip joint and abduction of the limb), and of the gastrocnemius muscle (followed by extension of the tarsus) were considered indicative of accurate needle positioning. When these were observed, the current intensity was progressively decreased to 0.5 mA while advancing the needle to a distance resulting in the same magnitude of muscular contraction. To locate the femoral nerve, the limb was abducted to a 90° angle and extended. As an anatomical landmark, the femoral artery was identified by palpation as proximally as possible. The stimulating needle was inserted immediately cranial to the femoral artery and perpendicular to the skin. The electro-stimulation was performed as previously described; the contraction of the quadriceps femoris muscle and the consequent stifle joint extension were considered indicative of a satisfactory nerve location. A volume of 0.2 mL/kg was injected, half at the sciatic site and half at the femoral site. The volume injected was based on a pilot study performed using 10 goats.
Pain assessment During surgery, relevant changes in physiological parameters (HR, fr, and MAP) and the occurrence of movements were considered as indicators of nociception. If movement occurred, propofol was administered IV as follows: for minor movements, (blinking, swallowing, and ear movements) 20 mg of propofol was administered, while 40 mg was given when major movements (limb flexion, extension, and head movements) occurred. IV methadone, 0.2 mg/kg, was administered when two of the following physiological parameters increased above baseline: HR > 10%, MAP > 25% or fr > 50%. Serum cortisol levels were determined in 36 animals equally distributed over the treatment groups at four time points: (1) 20 min before the beginning of anaesthesia (with the animal still penned) as the baseline (T 20); (2) immediately after the skin incision (T0); (3) 1 h after the incision (T60), and (4) 2 h after incision (T120) (Fig. 1). Cortisol serum levels were assayed using radioimmunoassay (RIA), according to a technique described previously (Blum et al., 1985). Post-operative data were collected at three time points: on the evening of the surgery after the animals had been returned to the barn following recovery from anaesthesia (day 1), and 24 h (day 2) and 48 h post-operatively (day 3). Since all goats did not undergo surgery simultaneously, the first time point (day 1) for each animal was scattered over 2–4 h post-operative period. Pain was always assessed by the same investigator (C.A.), blinded to the treatment. At each time point, observations included a total pain score and a 100 mm visual analogue scale (VAS). On day 1 the presence or absence of motor blockade and reaction to joint and wound palpation were also assessed. The total pain score included the following categories: a numerical rating scale (NRS), general and interactive behaviours, and physiological parameters (HR, fr). For the NRS, the observer estimated the degree of pain by assigning a score, ranging from 0 to 3, with 0 being no pain and 3 being unbearable pain. Evaluation of general behaviour was performed using a binary system based on the observed presence or absence of the following descriptors: abnormal posture, frequent posture change, vocalisation, teeth grinding, painful facial expression with
Fig. 2. Positioning of the goat in lateral recumbency and stimulating needle insertion for sciatic nerve block. The injection was only administered when the current was reduced to 0.5 mA and a twitch response was still elicited.
C. Adami et al. / The Veterinary Journal 188 (2011) 53–57 ears held back, lethargy and/or depression. For each of these descriptors, a score of 1 was assigned, and 0 meant that the event was not observed. For the category ‘interactive behaviour’, 0 indicated normal behaviour and a score of 3 indicated the greatest change in behaviour (0, alert and responsive; 1, comes to front after two calls; 2, comes to front after four calls; 3, no reaction, does not come to front or is aggressive). For the physiological parameters, 0 meant absent or minimal changes in HR and fr (<10%), 1 indicated an increase of 11–30%; 2, an increase of 31–50%; and 3, an increase of >50%, compared to pre-anaesthetic values. The sum of the scores resulting from these three categories was defined as total pain score. For the VAS score, the observer marked the estimated degree of pain on a 100 mm line, with 0 being no pain and 100 mm being the worst imaginable pain. Rescue post-operative analgesics (IM methadone, 0.2 mg/kg, every 3 h until the next pain assessment) were administered when animals showed a VAS of >4, or a total pain score of >8. Joint palpation was performed by applying increasing pressure with two fingers between condyles, whereas for the wound palpation, the pressure was applied to the skin near the surgical wound. The results were expressed in terms of presence or absence of reaction to palpation. Decreased or absent reaction to clamping of the toes of the operated limb and proprioceptive deficit were considered indicative of motor blockade.
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Fig. 3. Proportion of animals receiving intra-operative propofol. The number of animals within each group is shown in brackets. Statistical comparison was undertaken using Fisher’s exact test (each group is compared to C group), P < 0.05.
Statistical analysis To compare the intra-operative physiological variables (HR; MAP; SAP; DAP) among treatments, area under the curve (AUC) values were determined for each animal from data recorded from the incision time (time 0) until the end of surgery, and tested using one way analysis of variance analysis (ANOVA), followed by a Bonferroni multiple comparison test. To compare the cortisol serum levels among treatment groups over time, repeated measures ANOVA was used, followed by Tukey Kramer’s multiple comparison test. The total doses of rescue propofol received by each group, were analysed with one-way ANOVA, followed by the Bonferroni multiple comparison test, while the number of animals receiving propofol within each group was analysed using the Fisher exact test. Total pain score and VAS score were analysed with non-parametric tests (Kruskal Wallis one-way ANOVA, followed by Kruskal–Wallis multiple comparison Z value test). Proportions of animals presenting motor blockade and those reacting to either joint or wound palpation were analysed with the Fisher exact test. Statistical analyses were performed using commercially available software (NCSS, 2007). Values of P < 0.05 were considered significant.
Results General anaesthesia lasted between 35 and 185 min, mean (±SD) equal to 85 ± 30 min. Intra-operatively, two goats were found to show signs of cartilage degeneration and for this reason were excluded from the study. This was unexpected and slightly affected the accuracy of the block randomisation, as two more goats were added to replace the ones excluded. None of the goats included in the study required either intra-operative or post-operative rescue analgesia. Recovery was uneventful in all goats. The total intra-operative propofol dose was significantly higher in group C (400 mg) than in the bupivacaine groups (P = 0.01). The proportion of animals receiving propofol was significantly higher in group C than in groups 0.5 (P = 0.01) and 0.75 (P = 0.03) (Fig. 3). No statistically significant differences in HR, SAP, MAP and DAP were observed between groups. Compared to baseline, serum cortisol concentrations decreased at T0 and remained at values lower than at T 20 in each group until the end of general anaesthesia. In 67% of the animals in which cortisol levels were determined (n = 36), the sample at T60 was collected during recovery. At T120, a significant increase in cortisol concentrations, compared to the other time points, was observed in all groups. There was a statistically significant difference in cortisol levels between time points (P < 0.05), but no differences were observed between groups. Cortisol serum concentrations in animals that were anaesthetised versus awake at T60 are shown in Figs. 4A and 4B. At day 1, VAS score was significantly lower in group 0.75 than in groups C and 0.25 (P < 0.001), whereas the total pain score reached the highest value in group C (P = 0.001) (Figs. 5 and 6).
Fig. 4A. Mean cortisol serum concentrations (ng/mL) over time in animals still anaesthetised at T60. ANOVA repeated measures (each time point is compared to 20 min), P < 0.05.
Fig. 4B. Mean cortisol serum concentrations (ng/mL) over time in animals already awake at T60. ANOVA repeated measures (each time point is compared to 20 min), P < 0.05.
The proportions of animals presenting motor blockade and reacting to joint and wound palpation within each group is shown in Fig. 7. In groups 0.5 and 0.75, the motor blockade lasted more than 4 h. In group C, motor blockade was observed in one animal. No significant differences in VAS and total pain score among groups were observed at days 2 and 3.
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Fig. 5. VAS score at day 1. Kruskal Wallis one-way ANOVA; statistically significant difference between group 0.25 and group 0.75 and between group 0.75 and group C, P < 0.01.
Fig. 6. Total pain score at day 1. Kruskal Wallis one-way ANOVA; statistically significant difference between group C and all other groups, P < 0.01.
Fig. 7. Proportion of animals within each group which reacted to the joint and to the wound palpation. Fisher exact test, significant for P < 0.05 (each group is compared to C group).
Discussion In this study, we evaluated the technique and the quality of analgesia provided by the SFNB performed using three concentrations of bupivacaine in goats undergoing stifle arthrotomy. The lower intra-operative propofol dose, in addition to the lower VAS and total pain score achieved by groups 0.25, 0.5 and 0.75 com-
pared to group C, indicated that all bupivacaine concentrations provided better analgesia than saline. Superior analgesia was achieved in groups 0.5 and 0.75 compared with groups 0.25 and C, as suggested by the reduced reactions to joint palpation. The resulting motor blockade must also be considered as a major undesired side effect. The experiments were standardised such that each animal underwent the same experimental surgery, performed by the same surgical team with the same anaesthetic protocol and a fixed PE’Sevo. Therefore, even though the individual MAC for each animal was not determined, we could assume that all animals had a similar degree of unconsciousness on the basis of the clinical evaluation of anaesthetic depth performed before the beginning of the surgery. Movements occurring during general anaesthesia were considered a response to noxious stimuli. According to previous work, the amount of anaesthetic needed for immobility increases during noxious stimulation (Antognini and Carstens, 2002). Both hypnotics and analgesics play important roles in the suppression of movements during general anaesthesia (Bouillon et al., 2004; von Dincklage et al., 2009). In this study, propofol was chosen to provide immobility both for the need to readily suppress movements in case they occurred during surgery, and because the administration of further analgesics could have compromised the reliability of pain assessment. Goats in groups 0.5 and 0.75 needed significantly less propofol and this can be attributed to a more stable anaesthesia. Cortisol has been reported to correlate with acute pain in dogs, lambs and horses (Popilskis et al., 1993; Molony et al., 2002; van Dijk et al., 2003). In this study, the lack of difference in cortisol serum concentrations among treatment groups could be due to poor sensitivity of cortisol as a pain indicator, or to the fact that there was no difference in analgesia provided by performing the SFNB with bupivacaine or saline. Previous work has questioned the reliability of cortisol as a pain indicator. In horses undergoing arthroscopy, cortisol levels did not correlate with b-endorphin and catecholamine concentrations, or subjective pain score (Raekallio et al., 1997). Furthermore, endocrine response evaluated in two groups of lambs, one undergoing surgery and one control, showed that cortisol levels increased after the end of anaesthesia in all animals (Martín et al., 2001). These findings are in agreement with our results, since the sample at T120 was collected after recovery, when cortisol levels were higher compared to T0, T20, and T60. The significantly lower VAS and total pain scores of goats in which the sciatic-femoral block was performed with all concentrations of bupivacaine instead of saline at day 1 indicates that these animals had better analgesia than the control group. The lack of significant differences between treatments at day 2 and day 3 indicates that the beneficial effect of the SFNB was limited to the first 24 h, even if initiating analgesia prior to surgery may reduce postoperative pain, through a pre-emptive mechanism (Woolf and Chong, 1993). The reaction to joint palpation was inversely related to the presence of motor blockade. As animals presenting a motor blockade had a reduced or absent reaction to joint palpation, it may be assumed that they had a better analgesia compared to animals that retained complete motor function of the hind limb, and strongly reacted to joint palpation. However, the motor blockade was an undesirable side effect as it transitorily impaired the limb function, causing a certain degree of discomfort characterized by anxiety and behavioural changes. One animal in the control group presented transient motor blockade. The limb regained normal motor function 7 h after the SFNB. This effect may have resulted from an iatrogenic nerve lesion that occurred during the nerve location. This may have been a transitory impairment of the nerve function due to the pressure exerted by the volume injected, although accidental intra-neural
C. Adami et al. / The Veterinary Journal 188 (2011) 53–57
injection cannot be ruled out. Detecting an absence of twitch response with the current reduced to 0.2 mA has been described to decrease the risk of nerve injury while performing loco-regional anaesthesia (Hadzic and Vloka, 2004). In this study, the injection was administered with a positive twitch response at 0.5 mA, therefore intra-neural injection was possible. The reaction to wound palpation was not related to the presence of motor blockade, since even animals with evident motor blockade still tended to react to the wound palpation. Previous studies performed in humans undergoing total knee replacement showed that skin analgesia cannot be achieved by performing the SFNB alone (McNamee et al., 2002; Bergeron et al., 2009), but can be significantly improved by adding the obturator nerve block. In goats, the innervation of the skin covering the stifle joint is provided by the following spinal nerves: the lateral cutaneous femoral nerve (which supplies the cranio-lateral aspect), and the nerves ilioinguinal, iliohypogastric and genitofemoral, innervating the medial side (Popesko, 1984). However, a contribution of the obturator nerve to skin innervation has not been established in the goat, and the nerve is considered to be purely motor (Constantinescu, 2001) so it is unlikely that the addition of an obturator nerve block to SFNB may improve the quality of overall analgesia in goats. Conclusions One of the aims of this study was to describe the SFNB in goats. Based upon our observations, in this species the anatomical landmarks can be easily identified and the technique is feasible and rapidly performed. The SFNB performed with bupivacaine 0.5% and 0.75% offered satisfactory peri-operative analgesia in goats undergoing stifle arthrotomy. Unfortunately, the unilateral motor blockade observed in most of the animals of the 0.75 group provided a certain degree of distress that needs to be taken into account. We conclude that SFNB performed with 0.5% bupivacaine offered the best compromise between analgesia and side effects. Further studies will be necessary to assess the benefit of adding the obturator nerve block to provide analgesia to the skin of the medial aspect of the stifle joint. Conflict of interest statement None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper. Acknowledgements The authors thank ALLEVIA AG for the collaboration in the experimental work, Dr. Olivier Levionnois for his contribution in the study design and Dr. Shannon Axiak for the assistance in the manuscript revision. References Aithal, H.P., Amarpal, K., Pratap, K., Sigh, G.R., 1996a. Clinical effects of epidurally administered ketamine and xylazine in goats. Small Ruminant Research 24, 55– 64. Aithal, H.P., Amarpal, K., Pratap, K., Sigh, G.R., 1996b. Epidural ketamine and xylazine for hindquarter surgery in ruminants. A study of 35 clinical cases. Indian Veterinary Journal 74, 625–626. Antognini, J.F., Carstens, E., 2002. In vivo characterization of clinical anaesthesia and its components. British Journal of Anaesthesia 89, 156–166. Bailie, D., Ellenbecker, T., 2009. Severe chondrolysis after shoulder arthroscopy: a case series. Journal of Shoulder and Elbow Surgery 1, 1–6.
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The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Sciatic-femoral nerve block with bupivacaine in goats undergoing elective stifle arthrotomy q Chiara Adami a,*, Alessandra Bergadano a, Rupert M. Bruckmaier b, Michael H. Stoffel b, Marcus G. Doherr b, Claudia Spadavecchia a a b
Department of Clinical Veterinary Medicine, Anaesthesiology Division, Vetsuisse-Faculty, University of Berne, 3012 Berne, Switzerland Department of Clinical Research and Veterinary Public Health, Vetsuisse-Faculty, University of Berne, 3012 Berne, Switzerland
a r t i c l e
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Article history: Accepted 14 February 2010
Keywords: Analgesia Bupivacaine Sciatic-femoral nerve block Loco-regional anaesthesia Goat
a b s t r a c t The aim of this study was to describe the sciatic-femoral nerve block (SFNB) in goats and to evaluate the peri-operative analgesia when the goats underwent stifle arthrotomy. The animals were randomly assigned to one of four treatment groups: groups 0.25, 0.5 and 0.75 received 0.25%, 0.5% and 0.75% of bupivacaine, respectively, while group C (control group) received 0.9% NaCl. In all groups, the volume administered was 0.2 mL/kg. Intra-operatively, the proportion of animals receiving rescue propofol was significantly lower in groups 0.5 and 0.75, compared to group C. Post-operatively, the visual analogue scale (VAS) and total pain score were significantly higher in group C than in the other groups. Group 0.75 had the highest percentage of animals showing motor blockade. SFNB performed with bupivacaine resulted in better intra- and post-operative analgesia than SFNB performed with saline. Compared to the other concentrations, 0.5% bupivacaine resulted in satisfactory analgesia with acceptable side effects. Ó 2010 Elsevier Ltd. All rights reserved.
Introduction Pain assessment in ruminants has received less attention than in small animals as they rarely show classical signs of pain, such as vocalisation, restlessness or violent motor activity (Valverde and Gunkel, 2005). Due to anatomical similarities with the human stifle joint, small ruminants are becoming an increasingly common model for comparative orthopaedic research (Dowd et al., 1998). As these experimental procedures are invasive and painful, aggressive pain management in the intra-operative and early post-operative period is essential. The use of local and regional anaesthesia techniques has increased over the past decade as a key component of balanced analgesia in humans and small animals (Cox and Riedesel, 1997; Ramussen et al., 2006). The main advantages of using loco-regional anaesthesia as part of a balanced anaesthesia protocol are better analgesia (via blockage of peripheral pain pathways) and a decrease in the amount of opioids and inhalation anaesthetics needed to maintain anaesthesia, resulting in less associated side effects. Few techniques have been specifically described for small ruminants. Intra-articular injection of local anaesthetic drugs has been
q Part of the preliminary results of this study was presented at the AVA congress in Barcelona in October 2008. * Corresponding author. Tel.: +41 031 631 2791; fax: +41 031 631 2620. E-mail address: [email protected] (C. Adami).
1090-0233/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2010.02.008
reported to reduce post-operative pain in sheep undergoing stifle arthrotomy (Shafford et al., 2004). However, the technique is contraindicated if the experimental procedures aim to evaluate chondral regeneration due to the potential interaction of the local anaesthetic with the cartilage healing process (Bailie and Ellenbecker, 2009). Several studies have evaluated the efficacy of epidural anaesthesia in both sheep and goats (Aithal et al., 1996a,b; Mpanduji et al., 1999). The administration of analgesics and local anaesthetics into the epidural space is common practice in veterinary medicine and although it is effective in providing peri-operative analgesia for hindlimb surgeries, potential side effects and complications should be taken into account. For example, bilateral motor blockade often occurs with epidural anaesthesia but is undesired in ruminants as it may lead to discomfort and distress (Mpanduji et al., 1999). Moreover, as the caudal extension of the spinal cord can vary among individuals, the possibility of damaging the cauda equina when placing the needle in the lumbosacral epidural space may increase the risk of iatrogenic complications (Mpanduji et al., 2000). To our knowledge, there are no reports on the use of sciaticfemoral nerve block (SFNB) in goats. We hypothesised that in goats undergoing surgery involving the stifle joint the SFNB may be an effective, technically easy, inexpensive alternative to other previously described techniques. The aims of this study were therefore to describe the SFNB technique and to evaluate its peri-operative efficacy in goats undergoing stifle arthrotomy.
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Fig. 1. Experimental time table. C: blood sampling for cortisol serum measurement at the following time points: baseline ( 20 min), after incision (0), and 60 (60 min) and 120 (120 min) minutes after skin incision; A: beginning of general anaesthesia; SFNB: sciatic-femoral nerve block; S: surgery; a: VAS; b: total pain score; c: reaction to palpation (wound and joint); d: evaluation of presence or absence of motor blockade.
The study was designed as a prospective, block randomised, blinded, placebo controlled experimental trial.
Animals were randomly assigned to four treatment groups, each including 13 animals, as follows: goats of group 0.25 received bupivacaine 0.25% (Carbostesin 0.25%, AstraZeneca); goats of groups 0.5 and 0.75 received bupivacaine 0.5% and 0.75% (Carbostesin 0.5%, AstraZeneca; Bupivacaine 0.75%, Sintetica), respectively. Group C was used as the controls and received 0.9% NaCl. SFNBs were always performed by the same anaesthetist (C.A.), blinded to the treatment.
Animals
Surgery
Fifty-two Saanen goats, females, 2 years old, weighing 60 ± 3.2 kg, were used in this study. A thorough examination of each animal was performed on arrival to assess the health status. Exclusion criteria were pregnancy, sickness, abnormal posture or lameness, and intra-operative findings of cartilage defect. Prior to surgery, no food was provided for 24 h and access to water was restricted for 12 h. The experimental trial was performed with permission from the local committee for animal experimentation (Canton of Berne, Switzerland).
All goats underwent knee arthrotomy followed by the creation of three osteochondral defects (6 mm diameter, 0.8 mm depth), in the trochlea and in each condyle, respectively.
Materials and methods Study design
Anaesthesia A 14 G (80 mm) catheter was aseptically placed in the jugular vein for intravenous (IV) drug administration and blood sampling. Following pre-medication with IV midazolam (0.3 mg/kg, Dormicum, Roche) and IV methadone (0.05 mg/kg, Methadon, Streuli), anaesthesia was induced with IV ketamine (3 mg/kg, Narkan 100, Dr. E. Gräub) and propofol (1 mg/kg, Propofol, Fresenius). After endotracheal intubation, performed under laryngoscopic visualisation, anaesthesia was maintained with sevoflurane (Sevoflurane, Abbott) in air/oxygen (1:1) administered through a circle system. A constant end-tidal sevoflurane concentration (PE’Sevo) of 2.9%, equivalent to 1.25 the minimum alveolar concentration (MAC) (Steffey and Mama, 2007) was targeted during anaesthesia. Goats were instrumented with an electrocardiogram and an end-tidal gas analyser (Anandic Medical System, Datex-Ohmeda). The caudal auricular artery was cannulated for arterial blood pressure monitoring. Heart rate (HR), systolic arterial blood pressure (SAP), mean arterial blood pressure (MAP), diastolic blood pressure (DAP), respiratory rate (fr), end-tidal carbon dioxide tension (PE CO2), and PE’Sevo data were electronically recorded every 5 s on a computer from the beginning of general anaesthesia until the end of the surgical procedure. During the procedure animals received IV ringer lactate solution (5 mL/kg/h, Ringer Lactate, Bischel). If MAP fell <70 mm Hg, dopamine was infused at 5 lg/kg/min. Flunixin meglumine (1.1 mg/kg, Finadyne, Biokema) was administered IV at the end of the procedure, then intramuscularly (IM) once a day for the 4 days following. Nerve block The sciatic and femoral nerves were located using a nerve stimulator (TOF watch, Organon), according to techniques previously described in dogs (Campoy, 2008; Clark, 2008; Mahler, 2008; Mahler and Adogwa, 2008). For sciatic nerve location, the animals were placed in lateral recumbency with the (randomly assigned) operative leg uppermost (Fig. 2). The anatomical landmarks of the greater trochanter and the ischiatic tuberosity identified by palpation; a mark was then made at each point and a line was drawn between them. After aseptic preparation of the skin, a small incision was made with a needle at one-third of the distance from the great trochanter. The stimulating needle was then inserted through the incision at a 60° angle toward the great trochanter. Electrical stimulation was given at 1 Hz, starting at an intensity of 2.0 mA. Contractions of the biceps femoris, semitendinosus and semimembranosus muscles (with consequent extension of the hip joint and abduction of the limb), and of the gastrocnemius muscle (followed by extension of the tarsus) were considered indicative of accurate needle positioning. When these were observed, the current intensity was progressively decreased to 0.5 mA while advancing the needle to a distance resulting in the same magnitude of muscular contraction. To locate the femoral nerve, the limb was abducted to a 90° angle and extended. As an anatomical landmark, the femoral artery was identified by palpation as proximally as possible. The stimulating needle was inserted immediately cranial to the femoral artery and perpendicular to the skin. The electro-stimulation was performed as previously described; the contraction of the quadriceps femoris muscle and the consequent stifle joint extension were considered indicative of a satisfactory nerve location. A volume of 0.2 mL/kg was injected, half at the sciatic site and half at the femoral site. The volume injected was based on a pilot study performed using 10 goats.
Pain assessment During surgery, relevant changes in physiological parameters (HR, fr, and MAP) and the occurrence of movements were considered as indicators of nociception. If movement occurred, propofol was administered IV as follows: for minor movements, (blinking, swallowing, and ear movements) 20 mg of propofol was administered, while 40 mg was given when major movements (limb flexion, extension, and head movements) occurred. IV methadone, 0.2 mg/kg, was administered when two of the following physiological parameters increased above baseline: HR > 10%, MAP > 25% or fr > 50%. Serum cortisol levels were determined in 36 animals equally distributed over the treatment groups at four time points: (1) 20 min before the beginning of anaesthesia (with the animal still penned) as the baseline (T 20); (2) immediately after the skin incision (T0); (3) 1 h after the incision (T60), and (4) 2 h after incision (T120) (Fig. 1). Cortisol serum levels were assayed using radioimmunoassay (RIA), according to a technique described previously (Blum et al., 1985). Post-operative data were collected at three time points: on the evening of the surgery after the animals had been returned to the barn following recovery from anaesthesia (day 1), and 24 h (day 2) and 48 h post-operatively (day 3). Since all goats did not undergo surgery simultaneously, the first time point (day 1) for each animal was scattered over 2–4 h post-operative period. Pain was always assessed by the same investigator (C.A.), blinded to the treatment. At each time point, observations included a total pain score and a 100 mm visual analogue scale (VAS). On day 1 the presence or absence of motor blockade and reaction to joint and wound palpation were also assessed. The total pain score included the following categories: a numerical rating scale (NRS), general and interactive behaviours, and physiological parameters (HR, fr). For the NRS, the observer estimated the degree of pain by assigning a score, ranging from 0 to 3, with 0 being no pain and 3 being unbearable pain. Evaluation of general behaviour was performed using a binary system based on the observed presence or absence of the following descriptors: abnormal posture, frequent posture change, vocalisation, teeth grinding, painful facial expression with
Fig. 2. Positioning of the goat in lateral recumbency and stimulating needle insertion for sciatic nerve block. The injection was only administered when the current was reduced to 0.5 mA and a twitch response was still elicited.
C. Adami et al. / The Veterinary Journal 188 (2011) 53–57 ears held back, lethargy and/or depression. For each of these descriptors, a score of 1 was assigned, and 0 meant that the event was not observed. For the category ‘interactive behaviour’, 0 indicated normal behaviour and a score of 3 indicated the greatest change in behaviour (0, alert and responsive; 1, comes to front after two calls; 2, comes to front after four calls; 3, no reaction, does not come to front or is aggressive). For the physiological parameters, 0 meant absent or minimal changes in HR and fr (<10%), 1 indicated an increase of 11–30%; 2, an increase of 31–50%; and 3, an increase of >50%, compared to pre-anaesthetic values. The sum of the scores resulting from these three categories was defined as total pain score. For the VAS score, the observer marked the estimated degree of pain on a 100 mm line, with 0 being no pain and 100 mm being the worst imaginable pain. Rescue post-operative analgesics (IM methadone, 0.2 mg/kg, every 3 h until the next pain assessment) were administered when animals showed a VAS of >4, or a total pain score of >8. Joint palpation was performed by applying increasing pressure with two fingers between condyles, whereas for the wound palpation, the pressure was applied to the skin near the surgical wound. The results were expressed in terms of presence or absence of reaction to palpation. Decreased or absent reaction to clamping of the toes of the operated limb and proprioceptive deficit were considered indicative of motor blockade.
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Fig. 3. Proportion of animals receiving intra-operative propofol. The number of animals within each group is shown in brackets. Statistical comparison was undertaken using Fisher’s exact test (each group is compared to C group), P < 0.05.
Statistical analysis To compare the intra-operative physiological variables (HR; MAP; SAP; DAP) among treatments, area under the curve (AUC) values were determined for each animal from data recorded from the incision time (time 0) until the end of surgery, and tested using one way analysis of variance analysis (ANOVA), followed by a Bonferroni multiple comparison test. To compare the cortisol serum levels among treatment groups over time, repeated measures ANOVA was used, followed by Tukey Kramer’s multiple comparison test. The total doses of rescue propofol received by each group, were analysed with one-way ANOVA, followed by the Bonferroni multiple comparison test, while the number of animals receiving propofol within each group was analysed using the Fisher exact test. Total pain score and VAS score were analysed with non-parametric tests (Kruskal Wallis one-way ANOVA, followed by Kruskal–Wallis multiple comparison Z value test). Proportions of animals presenting motor blockade and those reacting to either joint or wound palpation were analysed with the Fisher exact test. Statistical analyses were performed using commercially available software (NCSS, 2007). Values of P < 0.05 were considered significant.
Results General anaesthesia lasted between 35 and 185 min, mean (±SD) equal to 85 ± 30 min. Intra-operatively, two goats were found to show signs of cartilage degeneration and for this reason were excluded from the study. This was unexpected and slightly affected the accuracy of the block randomisation, as two more goats were added to replace the ones excluded. None of the goats included in the study required either intra-operative or post-operative rescue analgesia. Recovery was uneventful in all goats. The total intra-operative propofol dose was significantly higher in group C (400 mg) than in the bupivacaine groups (P = 0.01). The proportion of animals receiving propofol was significantly higher in group C than in groups 0.5 (P = 0.01) and 0.75 (P = 0.03) (Fig. 3). No statistically significant differences in HR, SAP, MAP and DAP were observed between groups. Compared to baseline, serum cortisol concentrations decreased at T0 and remained at values lower than at T 20 in each group until the end of general anaesthesia. In 67% of the animals in which cortisol levels were determined (n = 36), the sample at T60 was collected during recovery. At T120, a significant increase in cortisol concentrations, compared to the other time points, was observed in all groups. There was a statistically significant difference in cortisol levels between time points (P < 0.05), but no differences were observed between groups. Cortisol serum concentrations in animals that were anaesthetised versus awake at T60 are shown in Figs. 4A and 4B. At day 1, VAS score was significantly lower in group 0.75 than in groups C and 0.25 (P < 0.001), whereas the total pain score reached the highest value in group C (P = 0.001) (Figs. 5 and 6).
Fig. 4A. Mean cortisol serum concentrations (ng/mL) over time in animals still anaesthetised at T60. ANOVA repeated measures (each time point is compared to 20 min), P < 0.05.
Fig. 4B. Mean cortisol serum concentrations (ng/mL) over time in animals already awake at T60. ANOVA repeated measures (each time point is compared to 20 min), P < 0.05.
The proportions of animals presenting motor blockade and reacting to joint and wound palpation within each group is shown in Fig. 7. In groups 0.5 and 0.75, the motor blockade lasted more than 4 h. In group C, motor blockade was observed in one animal. No significant differences in VAS and total pain score among groups were observed at days 2 and 3.
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Fig. 5. VAS score at day 1. Kruskal Wallis one-way ANOVA; statistically significant difference between group 0.25 and group 0.75 and between group 0.75 and group C, P < 0.01.
Fig. 6. Total pain score at day 1. Kruskal Wallis one-way ANOVA; statistically significant difference between group C and all other groups, P < 0.01.
Fig. 7. Proportion of animals within each group which reacted to the joint and to the wound palpation. Fisher exact test, significant for P < 0.05 (each group is compared to C group).
Discussion In this study, we evaluated the technique and the quality of analgesia provided by the SFNB performed using three concentrations of bupivacaine in goats undergoing stifle arthrotomy. The lower intra-operative propofol dose, in addition to the lower VAS and total pain score achieved by groups 0.25, 0.5 and 0.75 com-
pared to group C, indicated that all bupivacaine concentrations provided better analgesia than saline. Superior analgesia was achieved in groups 0.5 and 0.75 compared with groups 0.25 and C, as suggested by the reduced reactions to joint palpation. The resulting motor blockade must also be considered as a major undesired side effect. The experiments were standardised such that each animal underwent the same experimental surgery, performed by the same surgical team with the same anaesthetic protocol and a fixed PE’Sevo. Therefore, even though the individual MAC for each animal was not determined, we could assume that all animals had a similar degree of unconsciousness on the basis of the clinical evaluation of anaesthetic depth performed before the beginning of the surgery. Movements occurring during general anaesthesia were considered a response to noxious stimuli. According to previous work, the amount of anaesthetic needed for immobility increases during noxious stimulation (Antognini and Carstens, 2002). Both hypnotics and analgesics play important roles in the suppression of movements during general anaesthesia (Bouillon et al., 2004; von Dincklage et al., 2009). In this study, propofol was chosen to provide immobility both for the need to readily suppress movements in case they occurred during surgery, and because the administration of further analgesics could have compromised the reliability of pain assessment. Goats in groups 0.5 and 0.75 needed significantly less propofol and this can be attributed to a more stable anaesthesia. Cortisol has been reported to correlate with acute pain in dogs, lambs and horses (Popilskis et al., 1993; Molony et al., 2002; van Dijk et al., 2003). In this study, the lack of difference in cortisol serum concentrations among treatment groups could be due to poor sensitivity of cortisol as a pain indicator, or to the fact that there was no difference in analgesia provided by performing the SFNB with bupivacaine or saline. Previous work has questioned the reliability of cortisol as a pain indicator. In horses undergoing arthroscopy, cortisol levels did not correlate with b-endorphin and catecholamine concentrations, or subjective pain score (Raekallio et al., 1997). Furthermore, endocrine response evaluated in two groups of lambs, one undergoing surgery and one control, showed that cortisol levels increased after the end of anaesthesia in all animals (Martín et al., 2001). These findings are in agreement with our results, since the sample at T120 was collected after recovery, when cortisol levels were higher compared to T0, T20, and T60. The significantly lower VAS and total pain scores of goats in which the sciatic-femoral block was performed with all concentrations of bupivacaine instead of saline at day 1 indicates that these animals had better analgesia than the control group. The lack of significant differences between treatments at day 2 and day 3 indicates that the beneficial effect of the SFNB was limited to the first 24 h, even if initiating analgesia prior to surgery may reduce postoperative pain, through a pre-emptive mechanism (Woolf and Chong, 1993). The reaction to joint palpation was inversely related to the presence of motor blockade. As animals presenting a motor blockade had a reduced or absent reaction to joint palpation, it may be assumed that they had a better analgesia compared to animals that retained complete motor function of the hind limb, and strongly reacted to joint palpation. However, the motor blockade was an undesirable side effect as it transitorily impaired the limb function, causing a certain degree of discomfort characterized by anxiety and behavioural changes. One animal in the control group presented transient motor blockade. The limb regained normal motor function 7 h after the SFNB. This effect may have resulted from an iatrogenic nerve lesion that occurred during the nerve location. This may have been a transitory impairment of the nerve function due to the pressure exerted by the volume injected, although accidental intra-neural
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injection cannot be ruled out. Detecting an absence of twitch response with the current reduced to 0.2 mA has been described to decrease the risk of nerve injury while performing loco-regional anaesthesia (Hadzic and Vloka, 2004). In this study, the injection was administered with a positive twitch response at 0.5 mA, therefore intra-neural injection was possible. The reaction to wound palpation was not related to the presence of motor blockade, since even animals with evident motor blockade still tended to react to the wound palpation. Previous studies performed in humans undergoing total knee replacement showed that skin analgesia cannot be achieved by performing the SFNB alone (McNamee et al., 2002; Bergeron et al., 2009), but can be significantly improved by adding the obturator nerve block. In goats, the innervation of the skin covering the stifle joint is provided by the following spinal nerves: the lateral cutaneous femoral nerve (which supplies the cranio-lateral aspect), and the nerves ilioinguinal, iliohypogastric and genitofemoral, innervating the medial side (Popesko, 1984). However, a contribution of the obturator nerve to skin innervation has not been established in the goat, and the nerve is considered to be purely motor (Constantinescu, 2001) so it is unlikely that the addition of an obturator nerve block to SFNB may improve the quality of overall analgesia in goats. Conclusions One of the aims of this study was to describe the SFNB in goats. Based upon our observations, in this species the anatomical landmarks can be easily identified and the technique is feasible and rapidly performed. The SFNB performed with bupivacaine 0.5% and 0.75% offered satisfactory peri-operative analgesia in goats undergoing stifle arthrotomy. Unfortunately, the unilateral motor blockade observed in most of the animals of the 0.75 group provided a certain degree of distress that needs to be taken into account. We conclude that SFNB performed with 0.5% bupivacaine offered the best compromise between analgesia and side effects. Further studies will be necessary to assess the benefit of adding the obturator nerve block to provide analgesia to the skin of the medial aspect of the stifle joint. Conflict of interest statement None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper. Acknowledgements The authors thank ALLEVIA AG for the collaboration in the experimental work, Dr. Olivier Levionnois for his contribution in the study design and Dr. Shannon Axiak for the assistance in the manuscript revision. References Aithal, H.P., Amarpal, K., Pratap, K., Sigh, G.R., 1996a. Clinical effects of epidurally administered ketamine and xylazine in goats. Small Ruminant Research 24, 55– 64. Aithal, H.P., Amarpal, K., Pratap, K., Sigh, G.R., 1996b. Epidural ketamine and xylazine for hindquarter surgery in ruminants. A study of 35 clinical cases. Indian Veterinary Journal 74, 625–626. Antognini, J.F., Carstens, E., 2002. In vivo characterization of clinical anaesthesia and its components. British Journal of Anaesthesia 89, 156–166. Bailie, D., Ellenbecker, T., 2009. Severe chondrolysis after shoulder arthroscopy: a case series. Journal of Shoulder and Elbow Surgery 1, 1–6.
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