Comparison of anesthetic parameters of butorphanol and buprenorphine with lignocaine, ketamine, and propofol CRI in dogs

Introduction

The concept of balanced anesthesia is use of multiple agents to produce synergistic effects to provide adequate muscle relaxation, good analgesia and unconsciousness and avoid adverse effects of the individual drugs. It reduces the dose rates of individual drugs which will reduce the untoward effects and increases the safety. Propofol and ketamine alone or in combination, are commonly used for anesthesia in small animal practice. These drugs alone or in combination may not provide adequate muscle relaxation and profound analgesia. They can be combined with Butorphanol or Buprenorphine, an opioid analgesics. But literatures regarding such a combination is very limited. Continuous rate infusion (CRI) involves use of various intravenous anesthetic agents in combination at minimal doses to maintain low plasma concentrations of drugs and reduce use of any gaseous agents for maintenance of anesthesia. This involves use of different drugs to maintain muscle relaxation, analgesia and unconsciousness throughout the period of anesthesia. The present study aimed at comparing the anesthetic parameters with butorphanol-lignocaineketamine-propofol and buprenorphine-lignocaine-ketamine-propofol as continuous rate infusions (CRI) in dogs.

Materials and Methods

The present study was conducted in twelve healthy dogs presented for neutering at the Department of Veterinary Surgery and Radiology, Veterinary College Hassan. The animals were randomly divided into two groups (group A and group B), with each group comprising six dogs. All dogs of both the group were pre-medicated with atropine sulphate @ 0.04 mg/kg and meloxicam @ 0.2 mg/kg administered subcutaneously. Ten minutes later, administration of inj. xylazine @ 1 mg/kg IM was done for sedation. This followed by induction using propofol at 2 mg/kg IV, administered to effect in both the groups. After induction, group A received a loading dose comprising 2% lignocaine at 2 mg/kg, butorphanol at 0.2 mg/kg and ketamine at 2 mg/kg intravenously. Anesthesia maintained using a constant rate infusion (CRI) of butorphanol (0.2 mg/kg/hr), lignocaine (50 μg/kg/min), ketamine (40 μg/kg/min), and propofol (6 mg/kg/hr) in normal saline. For group B after induction, administration of loading dose of 2% lignocaine at 2 mg/kg, buprenorphine at 0.02 mg/kg, and ketamine at 2 mg/kg intravenously. Maintenance of anesthesia in this group achieved using a CRI of buprenorphine (2.5 μg/kg/hr), lignocaine (50 μg/kg/min), ketamine (40 μg/kg/min) and propofol (6 mg/kg/hr). For both the groups each drug drawn into separate sterile disposable syringes and then mixed with normal saline to achieve a final volume of 60 ml, suitable for the syringe pump used. The amount of each drug was calculated using the formula provided below. The flow rate of the continuous rate infusion (CRI) was set @ 60 ml/hr. Volume of drug added (ml) = dose of the drug (μg/kg/min) 𝑋 final volume of solution (ml) rate of flow of CRI (ml/kg/min) X concentration of drug (μg/ml) Anesthetic parameters viz., degree of palpebral reflex, degree of analgesia assessment using pedal reflex, degree of muscle relaxation using assessment of jaw tone reflex and eyeball position were recorded at before induction, immediately after induction, start of CRI at 0 th min, 15 th , 30 th , 45 th and 60 th min interval of anesthesia. Duration of anesthesia, time taken for recovery and quality of recovery were evaluated. Pedal reflex was recorded as a measure of depth of analgesia in the scale of 0-3. Degree of palpebral reflex was observed by blink in response to light tap on the medial or lateral canthus of eye in the scale of 0-3. Degree of muscle relaxation was observed by relaxation of jaw tone in the scale of 0-3. Reflexes graded from 0 to 3 using the score system as per Ahmad et al. (2011) [1] is shown in table 1.

The mean and standard errors for various parameters studied in both the groups were calculated using descriptive statistics.

Recorded data was analysed by student 't' test to compare between two groups.

Results

Reflexes at various interval were recorded before and after the start of CRI (Table 2). In the dogs of group A and group B, complete presence of palpebral reflex (score = 0) was noted prior to induction. After induction, in group A and group B the reflex varied between score 1 to 2. From the time continuous rate infusion (CRI) was initiated (0 minutes) until the end of surgery, the palpebral reflex was completely absent (score = 3) in both the groups. During the surgical plane of anesthesia, a complete loss of the palpebral reflex was observed in both groups.

In both group A and group B dogs, a complete presence of the pedal reflex (score = 0) was observed before induction. Following induction, the pedal reflex varied between pedal score 1 to 3 in group A and group B. At the start of the CRI (0 th min) group A pedal reflex was noted between the score 2 to 3 and group B it was score 3 for all the dogs. From the 15 th minute continuous rate infusion (CRI) until the end of surgery, the pedal reflex remained entirely absent (score = 3) in both the groups.

In both Group A and Group B dogs, a complete presence of the jaw tone (score = 0) was observed before induction. Following induction, the jaw tone score varied between the score 2 and 3 in group A and B. From the initiation of the continuous rate infusion (CRI) at 0 th minute up to the surgery, the jaw tone remained entirely absent (score = 3) in both the groups. Throughout the surgical plane of anesthesia, a total loss of the jaw tone was noted in both groups.

All the 12 animals of group A and group B had their eyeballs in ventromedial position throughout the period of anesthesia. Signs associated with recovery were time taken immediately after weaning of CRI (

Discussion

In both the groups from the start of CRI till the end of surgery a complete loss of the palpebral reflex was observed. These results were comparable to those reported by Bayan et al.

(2021) [3] , observing complete loss of palpebral reflex during the maintenance phase of anesthesia, with gradual return during recovery. This was consistent with the findings of Vijay et al. (2024) [10] , Chandramohan et al. (2024) [5] and Kenjale et al. (2022) [8] where similar reflex suppression and recovery patterns were noted in dogs undergoing CRI of different drug combinations. The absence of the palpebral reflex in all animals undergoing surgery is likely resulting from the synergistic action of the drugs administered as a continuous rate infusion for anesthesia maintenance.

In group A from the 15 th min of CRI till the end of surgery a complete loss of the pedal reflex was observed whereas in group B from the start of the CRI pedal reflex was abolished. Kenjale et al. (2022) [8] reported that the lack of the pedal reflex in all animals during the surgical procedure suggested a robust analgesic effect and a consistent surgical plane of anesthesia. Similarly, Vijay et al. (2024) [10] reported the same findings with the CRI of midazolam, ketamine, and lignocaine. Chandramohan et al. (2024) [5] also noted complete loss of pedal reflex from peak sedation until the end of anesthesia in dogs administered dexmedetomidine, lignocaine, ketamine, and propofol via CRI. The muscle relaxation was adequate in both groups for surgical procedures throughout the study period. The profound muscle relaxation observed in the current study could be due to the synergistic effects of the drugs (butorphanol/buprenorphine, propofol, ketamine, and lignocaine) used. This was in accordance with the findings of Kenjale et al. (2022) [8] and Vijay et al. (2024) [10] . Eyeball was ventromedial in all the animals throughout the period of anesthesia. This was similar with the findings of Kenjale et al. (2022) [8] suggesting a surgical plane of anesthesia attributing to the analgesia produced by the synergistic effect of the drugs, given as continuous rate infusion, for maintenance of anesthesia. Grimm et al. (2015) [6] reported that eyeball position during general anesthesia maintenance is a reliable indicator of anesthetic depth. Therefore, the ventromedial rotation of the eyeballs observed in the present study is suggestive of adequate depth of anesthesia.

In the present study, recovery time was quicker in group A compared to group B, the difference was not statistically significant, but longer recovery time in group B can be attributed to longer half-life of buprenorphine, this was similar to the findings of Burbaitė et al. (2024) [4] , reporting that buprenorphine is an overall superior anesthetic agent compared to butorphanol for dogs undergoing OHE. Time taken for return of pedal reflex in group A and group B showed statistical significant difference which can be attributed to superior analgesic effects compared to butorphanol providing an adequate period of effective postoperative analgesia reported by Warne et al. (2014) [11] , Barbarossa et al. (2017) [2] . The other recovery parameters in the current study for group A and group B did not differ much, which is in accordance with the report of Raušer et al.

(2002) [8] , reporting the time taken for return of eyeballs, head lift and standing unassisted are more strongly influenced by other drugs used in anesthesia than by the specific opioid used. The smooth recovery observed in the current study could also be due to the elevated serum concentration of propofol at the end of anesthesia which was put forth by Jones et al. (2024) [7] , noting that continuous infusion or bolus administration of propofol towards the end of anesthesia reduced the incidence of emergence delirium during recovery.

Conclusion

In conclusion, the anesthetic CRI combinations provided deep and satisfactory anesthesia with adequate analgesia and muscle relaxation for elective surgical procedure. The anesthetic maintenance was satisfactory with adequate depth of anesthesia for elective surgical procedure, adequate relaxation of muscle, loss of pedal and palpebral reflexes, safe and smooth recovery from anesthesia. However, buprenorphine CRI provided marginally better analgesia comparatively to butorphanol CRI.

Acknowledgement

AcknowledgmentsAuthors are thankful to Department of Veterinary Surgery and Radiology, Veterinary College, Hassan, Karnataka for their support.

References

1. Ahmad RA, Amarpal A, Kinjavdekar P, Aithal HP, Pawde AM, Kumar D. Effects of midazolam or midazolam-fentanyl on sedation and analgesia produced by intramuscular dexmedetomidine in dogs. Asian J Anim Sci. 2011;5(5):302-316.
2. Barbarossa A, Rambaldi J, Giunti M, Zaghini A, Cunto M, Zambelli D, et al. Pharmacokinetics of buprenorphine following constant rate infusion for postoperative analgesia in dogs undergoing ovariectomy. Vet Anaesth Analg. 2017;44(3):435-443.
3. Bayan H, Sarma KK, Rao GD, Kalita D, Dutta D, Phukan A. Effects of propofol and ketamine as induction agent to isoflurane and as continuous rate infusion on haematobiochemical parameters in dogs premedicated with glycopyrrolate, dexmedetomidine and butorphanol. Indian J Anim Res. 2021;1:6-15.
4. Burbaitė E, Čechovičienė S, Sarapinienė I, Karvelienė B, Riškevičienė V, Daunoras G, et al. Effects of medetomidine-butorphanol and medetomidinebuprenorphine on oxidative stress and vital parameters in dogs undergoing ovariohysterectomy. Animals. 2024;14(9):1349-1358.
5. Chandramohan S, Sooryadas S, Dinesh PT, Jineshkumar NS, Remya V, Anoop S, et al. Multimodal balanced general anaesthesia using tiletamine-zolazepam, butorphanol, dexmedetomidine, propofol, ketamine and lignocaine in dogs. Indian J Vet Surg. 2024;45:1-10.
6. Grimm K, Lamont L, Tranquilli WJ, Greene SA, Robertson S, editors. Veterinary anesthesia and analgesia. Hoboken: John Wiley & Sons; 2015. p. 1-720.
7. Jones H, Robson K, Maddox T, Alderson B. Incidence of and risk factors for poor recovery quality in dogs recovering from general anaesthesia-a prospective case control study. Vet Anaesth Analg. 2024;51(3):227-234.
8. Kenjale L, Varghese R, Dinesh PT, Sooryadas S, Umesh CG. Evaluation of xylazine-midazolam-lignocaineketamine continuous rate infusion (CRI) for maintenance in xylazine-butorphanol-midazolam-ketamine (XBMK) anaesthetised dogs. J Indian Vet Assoc. 2022;20(2):1522.
9. Raušer P, Lexmaulova L. Clinical comparison of medetomidine-butorphanol and medetomidinebuprenorphine combinations for intravenous premedication of general anaesthesia in the dog. Acta Vet Brno. 2002;71(1):69-76.
10. Vijay P, Patil M, Dilipkumar D, Bhagavantappa B, Kattimani SG. Evaluation of multimodal CRI maintenance anaesthesia for dogs undergoing different orthopaedic surgeries. Biochem Cell Arch. 2024;24(1):1-8.
11. Warne LN, Beths T, Holm M, Carter JE, Bauquier SH. Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats. J Am Vet Med Assoc. 2014;245(2):195-202.
12. Wolfensberger BR, Larenza MP. Balanced anaesthesia in the equine. Clin Tech Equine Pract. 2007;6(2):104110.
13. Lamont LA. Multimodal pain management in veterinary medicine: The physiologic basis of pharmacologic therapies. Vet Clin North Am Small Anim Pract. 2008;38(6):1173-1186.
14. Ortel S. Back to basics: Constant rate infusions. Vet Tech J. 2006;27(1):257-272.
15. Brock KA. Preanaesthetic use of atropine in small animals. Aust Vet J. 2001;79(1):24-25.
16. Murty KSVVS. Studies on preemptive analgesic effects in canine hysterectomy [M.V.Sc. thesis]. Hyderabad: Acharya N.G. Ranga Agricultural University; 2004. p. 1102.
17. Lamont LA, Mathews KA. Opioids, nonsteroidal antiinflammatories, and analgesic adjuvants. In: Lumb & Jones' veterinary anesthesia and analgesia. 4th ed. Baltimore: Lippincott Williams & Wilkins; 2007. p. 241271.
18. Pan HL, Wu ZZ, Zhou HY. Modulation of pain transmission by G protein-coupled receptors. Vet Pharmacol Ther. 2008;117(1):141-161.
19. Kay B. A double-blind comparison between morphine and buprenorphine in the prevention of pain after operation. Br J Anaesth. 1978;50(6):5-9.
20. Surbhi S, Kinjavdekar P, Amarpal A, Aithal HP, Pawde AM, Pathak MC, et al. Physiological and biochemical effects of medetomidine-butorphanol-propofol anaesthesia in dogs undergoing orthopaedic surgery. Indian J Vet Surg. 2010;31(2):101-104.
21. Messenger KM, Davis JL, LaFevers DH, Barlow BM, Posner LP. Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site. Vet Anaesth Analg. 2011;38(4):374-384.
22. Hisar: Chaudhary Charan Singh Haryana Agricultural University; 2007. p. 1-89.