Open Veterinary Journal, (2025), Vol. 15(4): 1803-1811

Research Article

10.5455/OVJ.2025.v15.i4.33

Evaluation of anesthetic, locomotor, and sedative scores for lumbosacral epidural analgesia using bupivacaine and bupivacaine-dexmedetomidine in sheep

Sultan Fadel Al-Haid¹, Sayed Fathi El-Hawari^1*, Adel Ibrahim Almubarak¹, Zakriya Ali Al Mohamad¹, Sherief Mohamed Abdel-Raheem², Hazem Assem Youssef³ and Ahmed Mohamed Abdallah³

¹Department of Clinical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia

²Department of Public Health, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia

³Department of Surgery, Anaesthesiology and Radiology. Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt

*Corresponding Author: Sayed Fathi El-Hawari. Department of Clinical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia. Email: selhawari [at] kfu.edu.sa

Submitted: 16/02/2025 Accepted: 07/04/2025 Published: 30/04/2025

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Abstract

Background: Lumbosacral epidural analgesia is one of the most important techniques for sheep anesthesia and is frequently used for surgery in caudal body regions.

Aim: This study aimed to evaluate the antinociceptive, locomotor, and sedative effects of lumbosacral epidural injection of bupivacaine alone or in conjunction with dexmedetomidine in sheep.

Methods: Nine clinically healthy mixed-breed sheep were used. Each sheep received either bupivacaine (BUP) alone or bupivacaine in combination with dexmedetomidine (BUP-DEX). The heart rate, heart rhythm, respiratory rate, and rectal temperature were monitored. Anesthetic onset, recumbency duration, and unassisted standing time were recorded. Analgesic, sedative, and locomotor scores were assessed using established numeric scales.

Results: Analgesia onset was noted after 6.50 ± 2.75 minutes in the BUP group and after 4.33 ± 0.67 minutes in the BUP-DEX group. Sheep showed a tendency for recumbency in the BUP group at 3.33 ± 1.28 minutes after epidural injection and at 3.00 ± 0.68 minutes after epidural injection in the BUP-DEX group. Animals tended to stand earlier in the BUP group (199.83 ± 23.55 minutes) than in the BUP-DEX group (496.00 ± 82.97 minutes) (p=0.014). Marked sedation was noted in the BUP-DEX group. Motor block was detected in both groups. The analgesic score was more intense and had a longer duration in BUP-DEX than in BUP. Minimal cardiorespiratory changes were observed in BUP-DEX.

Conclusion: Briefly using of bupivacaine-dexmedetomidine mixture for epidural anesthesia is an important technique in sheep subjected to long-term surgical operations in the tail, perineal, inguinal, hind limb, flank, and umbilical regions with sufficient sedation, long-term recumbency, and minimal side effects.

Keywords: Bupivacaine, Dexmedetomidine, Epidural anesthesia, Sheep.

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Introduction

General anesthesia is rarely used in ruminants because it can result in fatal complications such as vomiting, salivation, and subsequent drenching pneumonia (Dadafarid and Najafpour, 2008). Epidural regional anesthesia, which is free from fatal complications, is, therefore, the most popular anesthetic regimen before performing diagnostic, obstetric, and surgical interventions in small ruminants (Sadegh et al., 2009). Epidural anesthesia resulted in a wide area of desensitization, including the perineal region, inguinal region, and upper part of the rear limbs (Skarda and Tranquilli, 2007; Khajuria et al., 2014). Although many locations for epidural infiltration have been previously described in the literature (Awaad and Fathy, 2018), lumbosacral epidural injection remains the most frequently used method in small ruminants (Lemke and Dawson, 2000; Marzok et al., 2022). Regarding epidural anesthetic drugs, lidocaine (intermediate duration of action) is the most frequently described drug, although long-duration anesthetics (bupivacaine) may also be used (Skarda and Tranquilli, 2007; Rioja, 2015). However, sheep can be subjected to local or regional anesthesia under manual restraint with or without sedation. Historically, local anesthetic drugs have been the most widely used class of drugs for epidural anesthesia (Dadafarid and Najafpour, 2008).

Bupivacaine is a long-lasting local anesthetic drug that is useful in small ruminant surgery, especially when prolonged blockade is required. Similar to other local anesthetic drugs used epidurally, bupivacaine may cause some physiological disturbances include; tympany (due to long-lasting recumbency), sleepiness, and tremors (Lucky et al., 2007). However, no adverse effects were observed on biochemical analysis, complete hematological examination, and blood gas analysis were detected (Singh et al., 2007). Moreover, using a smaller concentration of bupivacaine (0.25%) decreased the anesthetic duration but resulted in increased efficacy and safety of epidural injections. As bupivacaine is a long-acting anesthetic drug, it also provides longer postoperative analgesia (Derossi et al., 2015).

Dexmedetomidine is the dextrorotatory isomer of medetomidine, which is highly selective for alpha-2-adrenoreceptors, so it has more sedative and analgesic effects than other alpha-2 agonists with minimal cardiovascular depression (Murrell and Hellebrekers, 2005). In humans, epidural injection of low doses of dexmedetomidine provides sufficient synergistic effect with local anesthesia, increasing the anesthetic duration, strengthening the analgesic effect, and reducing possible side effects (Zhang et al., 2017). In dogs and cats, epidural injection of dexmedetomidine has the aforementioned advantages (Campagnol et al., 2007; Souza et al., 2010).

A lumbosacral epidural is usually performed using local anesthetic drugs because of the presence of a high density of alpha-2 receptors in the lamina II of the dorsal horn at the spinal cord in sheep (Kãstner, 2006). We hypothesized that injection of alpha-2-adrenonoceptor agonist in the lumbosacral epidural space will promote analgesic effects. To the best of our knowledge, this is the first study to describe the use of lumbosacral epidural co-injection of bupivacaine-dexmedetomidine in sheep. In the present study, we investigated the anesthetic, locomotor, sedation, and cardiopulmonary effects of epidural injection of bupivacaine alone and co-injection of dexmedetomidine-bupivacaine mixture in conscious sheep. Our hypothesis was that epidural co-injection of dexmedetomidine-bupivacaine would provide excellent sedation, more potent analgesia, and a longer duration of analgesia in sheep than using bupivacaine alone.

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Materials and Methods

Ethical approval

The present study was conducted according to the Animal Care Committee of King Faisal University (Reference no. KFU-REC-2024-ETHICS2046).

Animals

A total of nine apparently healthy, mixed-breed female sheep weighing 25.83 ± 3.55 kg and aged 15.83 ± 5.95 months were included. Animals included in the current study were selected on the basis of normal physical examination, complete blood count, and kidney and liver function tests.

Study design

An experimental crossover design study with a washout interval of 14 days was performed, as previously described by Marzok et al. (2022). Each sheep received 0.5 mg/kg^-1 of 0.5 % bupivacaine (Bupivacaãne Merk^®, Merkgénériques, France) (BUP) alone or 0.5 mg/kg^-1 bupivacaine in combination with dexmedetomidine 2.5 μg/kg^-1 (BUP-DEX) (0.5 mg/ml; Dexdomitor; Orion Corporation, Finland). In all treatments, injected anesthetic drugs were completed to reach a volume of 0.2 ml/kg^-1 by adding 0.9% sodium chloride to the calculated dose. The injection of epidural drugs was performed over 1 minute for all treatments. For the experimental epidural injection, animals were randomly selected, and the evaluator was blinded to the anesthetic drugs. The injection site was clipped, cleaned, and disinfected using an antiseptic solution. The injection was performed while the sheep were in a standing position using a Tuohy needle (18G × 3.5’inches”GALENA, Galena Medical Corporation, Istanbul, Turkey). The needle was inserted at the intersection between the last lumbar and first sacral vertebrae at a 90° angle into the lumbosacral space. When the needle point was judged to have penetrated the ligamentum flavum, then the needle directed ventro-cranial at an angle of approximately 30°. Confirmation that the needle had entered the epidural space was obtained through suction of the hanging drop from the needle hub or easy and no resistance injection with 0.2 ml of 0.9% NaCl. In a randomized order at weekly intervals, each sheep received either bupivacaine hydrochloride alone or 0.5 mg/kg^-1 bupivacaine co-infusion with dexmedetomidine 2.5 μg/kg^-1.

Study evaluation

The epidural injection time was zero for all examined animals. The onset of analgesia (desensitization of the tail or perineal areas), time of recumbency after epidural injection, and time of unaided standing after recumbency were recorded. The period of recumbency was calculated by subtracting the time of recumbency from the time of unaided standing.

Vital signs, including heart rate (HR), respiratory rate (RR), and rectal temperature (RT), were assessed. Heart rate (beats per minute, bpm) was assessed via thoracic auscultation, using a stethoscope, of the fourth left intercostal space for 1 minute. In addition, heart rhythm was evaluated, with normal rhythmic heart beats represented by 0 and arrhythmic heart beats represented by 1. The respiratory rate (breaths per minute) was evaluated by recording the thoracic movements in 1 minute. Rectal temperature (RT) was measured using a digital thermometer. The numerical sedation score was evaluated to detect the central effects produced by the absorption of drugs from the epidural space. The motor blockade score was designed to evaluate motor blockage via; the presence of ataxia, the ability of the sheep to walk, and even the degree of ataxia. Loss of sensation (anti-nociception score) was evaluated by applying noxious stimuli (pin-prick test) using an 18-gauge needle and pressure from mosquito artery forceps (closed to the first ratchet) to the examined region. The stimulus was applied to the tail, perineal, inguinal, hind limb, flank, and umbilical regions. The motor and antinociception scores used in the current study were modified from those previously described by Al-Ali et al. (2023) (Table 1). Collectively, cardiopulmonary parameters, sedation scores, motor blockade scores, and antinociception scores were recorded at the baseline (before drug injection) and at 5, 10, 20, 30, 60, 90, 120, 180, 240, 300, 360, 420, 480, 540, 660, and 720 minutes after epidural injection in each animal.

Statistical analysis

Statistical analyses were performed using commercial software (SPSS for Windows, United States, version 20). The Kolmogorov-Smirnov test was used to determine whether the data were normally distributed or not. Data were presented as scores (e.g., antinociceptive, sedation, and locomotor) that were not normally distributed, the Mann-Whitney U test was used to compare the two groups, and the Wilcoxon test was used to compare data for each time interval against baseline values. The results for these variables are presented as medians and ranges. Normally distributed data are presented as mean ± SE. Comparisons between the two groups for normally distributed variables were made using an independent samples t-test. Variables such as heart rate, respiratory rate, rectal temperature, and heart rhythm were found to be normally distributed, and they were analyzed using the independent samples t-test to compare the two groups at each time point. A significance level of p < 0.05 was used for all statistical tests to determine significant differences between groups.

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Results

The onset of analgesia was observed after 6.50 ± 2.75 minutes in the BUP group and after 4.33 ± 0.67 minutes in the BUP-DEX group, with no significant difference between the groups (p=0.46). Sheep showed a tendency for recumbency in the BUP group at 3.33 ± 1.28 minutes post epidural injection and at 3.00 ± 0.68 minutes post epidural injection in the BUP-DEX group, without significant difference between groups (p=0.83). Animals tended to stand earlier in the BUP group (199.83 ± 23.55 minutes) than in the BUP-DEX group (496.00 ± 82.97 minutes) (p=0.014). Sheep injected with a mixture of bupivacaine and dexmedetomidine showed 2.5-fold more recumbency duration than sheep injected with bupivacaine alone (493.0 ± 82.9 minutes and 196.5± 22.6 minutes, respectively) (p=0.017). The sedation score level started to increase 10 minutes after the epidural injection of the bupivacaine/dexmedetomidine mixture and lasted for 300 minutes after the epidural injection. Mild sedation was noted in the BUP group from 10 to 120 minutes after epidural injection. Significantly higher sedation was noted in BUP-DEX than in BUP between 10 and 300 minutes after epidural injection (Table 2). Compared with baseline values, motor blockage was detected in the BUP group between 5 and 240 minutes after epidural injection, whereas it was noted between 5 and 360 minutes in the BUP-DEX group. The BUP-DEX group had a significantly higher motor blockage at 120, 180, 240, and 300 minutes (p=0.019, 0.002, 0.005, and 0.007, respectively) (Table 3).

Regarding antinociception scores, desensitization in the tail area was more intense in the BUP-DEX group than in the BUP group at 5, 180, 240, and 300 minutes (p=0.007, 0.019, 0.002, and 0.003, respectively). However, compared with baseline values, desensitization at the tail area has longer duration in the BUP-DEX group than in the BUP group (360 and 120 minutes, respectively). At the perineal region, the antinociception score was higher in the BUP-DEX group than in the BUP group at 180, 240, and 300 minutes (p=0.019, 0.007, and 0.002, respectively). Desensitization of the perineal region lasted between 5 and 120 minutes after epidural injections in the BUP group, while it lasted for a longer duration in the BUP-DEX group (5–360 minutes). A comparison between the treatment groups revealed higher and more intense desensitization in the inguinal region at 5, 120, 180, 240, and 300 minutes in the BUP-DEX group than in the BUP group (p=0.04, 0.02, 0.002, 0.002, and 0.002, respectively). However, comparison with baseline values revealed that desensitization at the inguinal region in the BUP group lasted from 5 to 120 minutes, while it lasted for 5–360 minutes in the BUP-DEX group. Hind limb desensitization was higher in BUP-DEX than BUP at 120, 180, 240, and 300 minutes (p=0.002, 0.003, 0.005, and 0.002, respectively). Compared with baseline values, maximal desensitization of the hind limb was detected at 5–120 minutes in the BUP group and at 5–300 minutes in the BUP-DEX group. At the umbilical region, the anesthetic effect of bupivacaine alone lasted from 5 to 120 minutes, while it lasted from 5 to 360 minutes in bupivacaine-dexmedetomidine mixture. However, the BUP-DEX combination exerted a higher anesthetic effect than BUP alone at 5, 180, 240, and 300 minutes (p=0.01, 0.002, 0.002, and 0.002, respectively). Flank region anesthesia was more intense in BUP-DEX than BUP at 180, 240, and 300 minutes (p=0.002, 0.002, and 0.002, respectively). Compared with baseline values, anesthesia of the flank region lasted for 120 minutes in the BUP group while it lasted for 360 minutes in the BUP-DEX group (Table 4).

Table 1. Description of the numeric scales used to evaluate antinociception, sedative, and motor block scores.

Table 2. Responses of sheep to sedation score (median and range) over times. (BUP=Bupivacaine group, BUP-DEX=Bupivacaine- Dexmedetomidine group).

Table 3. Responses of sheep to motor block score (median and range) over times. (BUP=Bupivacaine group, BUP-DEX=Bupivacaine-Dexmedetomidine group).

Compared with the baseline, the cardiorespiratory parameters showed mild bradycardia in the BUP-DEX group. This bradycardia was transient and appeared 10–30 minutes after epidural injection. No significant changes were noticed in the BUP group compared with baseline values, and a slight decrease in HR was detected in the BUP-DEX group compared with the BUP group at 240 and 300 minutes post epidural injection (p=0.047 and 0.025, respectively). Arrhythmia was noted in the BUP-DEX group at 5 minutes (p=0.031) and 300 minutes (p=0.031) after epidural injection. The respiratory rate was lower in BUP-DEX than in baseline values at 120, 180, 240, and 300 minutes (p=0.008, 0.023, 0.028, and 0.024, respectively). In addition, RR was significantly lower in BUP-DEX than BUP at 300 minutes (p=0.001). Rectal temperature was not significantly different between the two treatment groups or between each group and the baseline values (Fig. 1).

Table 4. Results of antinociceptive score in examined sheep (median and range) over times. (BUP=Bupivacaine group, BUP-DEX=Bupivacaine-Dexmedetomidine group).

Fig. 1. This graph illustrates cardiopulmonary changes; A represent changes in heart rate (HR), B represent changes in rectal temperature (RT), and C represent changes of respiratory rate (RR) at various time points following the epidural administration of bupivacaine (BUP) or bupivacainedexmedetomidine combination in the lumbosacral space of sheep.

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Discussion

The current study aimed to investigate the extent of enhancement resulting from the addition of dexmedetomidine to epidurally injected bupivacaine in sheep. Multimodal epidural anesthesia has been previously described by several authors in sheep (Dadafarid and Najafpour, 2008; Rostami and Vesal, 2012; Derossi et al., 2012; Imani et al., 2020; Rashid et al., 2024). During epidural injection, bupivacaine and dexmedetomidine have different modes of action. Bupivacaine mainly acts on the cell membrane sodium channels by inhibiting the transmission of noxious stimuli, and it may also exert effects on synaptic transmission and presynaptic inhibition of calcium channels (Chen et al., 2002). Dexmedetomidine is an alpha-2 agonist that produces potent analgesia by activating alpha-2 adrenergic receptors (α2A/D, α2C) in the substantia gelatinosa of the dorsal horn in the spinal cord and inhibits the release of norepinephrine (Shah and Ding, 2014).

The current study revealed no difference in the onset of anesthesia between BUP and BUP-DEX. The same results were recorded previously in sheep in which dexmedetomidine had no effect on the anesthetic onset of epidurally administered lidocaine (Rostami and Vesal, 2012). However, the onset of anesthesia in the BUP group (6.50 ± 2.75 minutes) was somewhat similar to previous results obtained in sheep (9.5 ± 0.9 minutes) (Dadafarid and Najafpour, 2008), while it differs from previous results recorded in goat (17–41 ± 9 seconds) (Kiranjeet et al., 2015). Although sheep and goats are considered small ruminants, they respond differently to anesthetic drugs. For instance, goats are more sensitive to alpha-2 adrenoceptors than sheep (Shah and Ding, 2014). The time of motor blockage in the current study, either in the BUP or BUP-DEX groups, was earlier than the time of desensitization in sheep. The same result was recorded previously in dogs anesthetized epidurally using bupivacaine (Gãmez et al., 2000). Although bupivacaine alone produced mild to moderate ataxia in buffaloes injected with a low dose of 0.125 mg/kg^-1 (Singh et al., 2009) and in sheep injected with 0.5 mg/kg^-1 bupivacaine (Dadafarid and Najafpour, 2008), our results indicated the presence of severe ataxia in sheep injected with a higher dose of bupivacaine 0.5 mg/kg^-1. This may be due to the injection of anesthetic drugs or their migration by gravity to the bottom of the spinal canal, where motor nerves are located (Freire et al., 2010). Sheep injected with a mixture of bupivacaine and dexmedetomidine showed a 2.5-fold longer recumbency duration than sheep injected with bupivacaine alone. This is due to the potentiating effect of dexmedetomidine (alpha 2 adrenoceptors), as previously described by many authors (DeRossi et al., 2005; Rostami and Vesal, 2012; Al-Ali et al., 2023; Rashid et al., 2024; Shamsudeen et al., 2024).

Although the sheep in the current study administered a bupivacaine-dexmedetomidine combination showed sedation started 10 minutes post epidural injection and lasted to 300 minutes post injection. This result was due to the systemic absorption of dexmedetomidine from the extradural space of the spinal canal into circulation and subsequent supraspinal effects (Singh et al., 2009). Analgesia (anti-nociception score) was detected more intensely in the BUP-DEX group than in the BUP group at the initiation of anesthesia (5 minutes post epidural injection), especially at the tail, umbilical, and inguinal regions. This improvement in analgesic effect is due to the binding of alpha-2 agonists with receptors in the substantia gelatinosa of the dorsal horn of the spinal cord, where modulations of nociceptive signals are likely to be initiated. The presynaptic and postsynaptic inhibitory effects of alpha-2 agonists are also responsible for their antinociceptive action (Shah and Ding, 2014). The same results were detected previously when adding dexmedetomidine to lidocaine for epidural injection in sheep (Shamsudeen et al., 2024). Longer duration (5–360 minutes) and more intense analgesia were seen in sheep injected with bupivacaine-dexmedetomidine combination at different examined regions (tail, perineal, inguinal, umbilical, and flank regions), whereas sheep injected with bupivacaine only showed analgesia for 5–120 minutes in all tested regions. The prolonged duration of analgesia seen in the BUP-DEX group was previously described by Shamsudeen et al. (2024) in sheep, whereas the author found that the medetomidine treatment group provides longer analgesia than the lidocaine or lidocaine-xylazine groups (190–230 minutes). Moreover, significantly greater analgesia was previously detected in sheep injected epidurally with the lidocaine-dexmedetomidine mixture (239.56 ± 19.48 minutes) (Rostami and Vesal, 2012).

Minimal cardiorespiratory changes were seen in the current study. Mild and transient bradycardia was observed in sheep injected with a bupivacaine-dexmedetomidine combination (Murrell and Hellebrekers, 2005). These findings counteract other findings in a previous report of goats injected epidurally with a lidocaine-medetomidine mixture, whereas bradycardia was seen during all periods of anesthesia (Al-Ali et al., 2023). Moreover, in previous reports, bradycardia was not observed in donkeys injected epidurally with dexmedetomidine (Hamed et al., 2017). However, mild bradycardia, arrhythmia, and oligopnea detected in the current study were previously described in the literature for sheep and dogs administered dexmedetomidine (Murrell and Hellebrekers, 2005; Kutter et al., 2006; Shah and Ding, 2014). Moreover, the results of cardiorespiratory parameters in the current study for both groups were within the normal acceptable clinical ranges and did not require further intervention for correction.

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Conclusion

Bupivacaine epidural injection in sheep provides satisfactory analgesia for the perineal, tail, inguinal, flank, hind limb, and umbilical regions and lasts for 120 minutes. Epidural injection of the bupivacaine-dexmedetomidine mixture provides much more intense analgesia and lasts for 360 minutes in the same regions. The onset of analgesia ranged between 5 and 8 minutes in both groups. Locomotor paralysis occurred in both groups before the onset of desensitization. Marked sedation was observed in sheep anesthetized by bupivacaine-dexmedetomidine (10–300 minutes) after epidural injection. The duration of recumbency in the BUP-DEX group was 2.5-fold greater than that in the BUP group. Minimal cardiorespiratory changes occurred in bupivacaine-dexmedetomidine epidural injection in sheep. No post-anesthetic complications, such as tremors, tympany, regurgitation, or apnea, were noted in this study. This type of multimodal epidural injection is important in clinical anesthesia and provides excellent anesthesia for long-term operations in the caudal abdominal, pelvic, and hind limb regions.

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Acknowledgment

This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia [Grant No. KFU 251312].

Conflict of interest

The authors declare no conflicts of interest regarding the publication of this article.

Funding

This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia [Grant No. KFU 550].

Authors’ contributions

All authors contributed equally to this study.

Data availability

All data related to this study are included within the manuscript.

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