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Abstract

Objectives

The objective of this study was to assess the intraoperative analgesic effect of preoperative infiltration of the incision site with lidocaine or a mixture of lidocaine with bupivacaine in cats undergoing ovariohysterectomy (OHE).

Methods

This was a prospective, randomised clinical study. Healthy female intact cats (n = 75) undergoing OHE under medetomidine–ketamine–buprenorphine anaesthesia were assigned randomly into three treatment groups (n = 25 per group) to receive one of two local anaesthesia protocols or placebo preoperatively in the midline incision: lidocaine 1.5 mg/kg (group GL) or mixture of lidocaine 1 mg/kg and bupivacaine 1 mg/kg (group GLB) or sodium chloride 0.9% (control group). Blood pressure, heart and respiratory rate, temperature, muscle tonus and pupillary reflex were registered during surgery. During recovery, the cats were observed for side effects. Postoperative analgesia was provided with meloxicam (0.2 mg/kg). Most cats were rechecked 2 weeks postoperatively to remove skin sutures.

Results

There was no significant difference between groups regarding breed, age, body weight, surgical time and postoperative complication rate. The majority of the cats (60%) included in the control group received a supplemental bolus of propofol during surgery, when compared with 43% and 44% of the cats included in the GL and GLB groups, respectively. Heart rate was significantly higher (P <0.05) in the control group at the time of excision of the second ovary and the uterine body. Mean arterial pressure (MAP) was stable in both treatment groups; in contrast, it tended to increase in the control group. Heart rate and MAP were similar between treatment groups.

Conclusions and relevance

Preoperative incisional block with only lidocaine or combined with bupivacaine seems to produce a similar intraoperative analgesia in cats undergoing OHE. Despite the similar intraoperative analgesic effect between treatment groups, the combination of lidocaine and bupivacaine reduced the required doses, and had a faster onset of action and prolonged effect.

Introduction

Feline ovariohysterectomy (OHE) is one of the most common surgical procedures in veterinary practice and is widely used to control feral cat populations.^1,2 Low-cost spaying programmes are very popular and often used as part of the practical training of veterinary students. In such programmes, preoperative assessment, anaesthetic and analgesic protocols are usually basic. The lack of surgical experience in students also results in rather long operative times. OHE is considered a moderately painful abdominal surgery, and yet recognising pain in cats is particularly challenging owing to subtle behavioural changes when it occurs.³ Nevertheless, evaluation of physiological signs during surgery can be used to assess an acute nociceptive response, which includes pale mucous membranes, and increased blood pressure, heart rate (HR) and respiratory rate.^3–5

Effective perioperative pain management is better achieved by multimodal analgesia, which combines classes of drugs and techniques that target multiple sites in pain pathways.^6,7 One simple way to deliver multimodal analgesia in OHE is the incorporation of a local anaesthetic, in combination with systemic analgesic drugs.^8,9 Additionally, previous studies attribute antimicrobial and immunomodulating properties to local anaesthetic agents, and show that the agents do not impair wound healing.^10,11

Bupivacaine and lidocaine are some of the most common local anaesthetics used in companion animals.¹ Lidocaine has a relatively faster onset (10–15 mins), but an intermediate duration of action (60–120 mins), whereas bupivacaine has a slower onset to reach full effect (20–30 mins) but a longer duration of action (240–360 mins).^12,13 When both drugs are combined, they allow a faster onset of action and prolonged effect, and the doses required are smaller.^3,12 Cats are considered to be more susceptible than dogs to local anaesthetic toxicity.¹² Such adverse reactions are uncommon and can be divided into local tissue toxicity or systemic reactions due usually to an accidental intravascular injection.¹⁴ Most of the toxic signs involve the cardiovascular and central nervous system, and may lead to cardiac arrhythmias, tremors, convulsions and seizures.¹²

There have been few studies performed in cats undergoing OHE to evaluate the combination of local anaesthesia with general anaesthesia to improve perioperative analgesia.^15–18 In one study, the use of incisional and intraperitoneal lidocaine improved the perioperative analgesia and decreased supplemental anaesthetic requirement.¹⁸ By contrast, incisional bupivacaine alone was found insufficient to provide analgesia following OHE in cats.¹⁷ However, it was reported to be effective in dogs.^19,20

This study investigates the intraoperative analgesic effect of preoperative infiltration of the incision site with lidocaine or a mixture of lidocaine with bupivacaine in cats undergoing OHE. We hypothesised that supplementing general anaesthesia with an incisional block will result in a significantly lower nociceptive response during surgery. We also hypothesised that the lidocaine combined with bupivacaine would improve intraoperative analgesia compared with the use of lidocaine alone. In addition, it was hypothesised that the combination of lidocaine with bupivacaine may reduce the doses required.

Materials and methods

Animals

This study was approved by Uppsala Ethical Committee, Uppsala, Sweden (number C36/15). The Board of Agriculture approved the use of client-owned cats in this study. This study was performed in the context of a low-cost veterinary student spaying programme. Seventy-five healthy female cats of different breeds, scheduled for elective OHE, were included in a randomised, prospective, blinded, controlled, clinical trial. Informed written owner consent was obtained in each case prior to the study. Cats were admitted to the Small Animal Clinic at Swedish University of Agricultural Sciences, in the early morning and were returned to their owner later the same day. All cats were considered healthy, based on medical history and complete physical examination. Exclusion criteria were fractious temperament, cardiac arrhythmias, pregnancy, lactation, age <6 months or >7 years, body weight >5 kg and clinical signs of disease.

Anaesthesia and surgery

All cats were fasted overnight but had access to water until arrival at the hospital. Premedication consisted of 0.02 mg/kg medetomidine (Sedator; Dechra) and 0.2 mg/kg meloxicam (Metacam for Cats; Boehringer), both injected subcutaneously, and 0.01 mg/kg buprenorphine (Vetergesic; Indivior) injected in to the lumbosacral muscles. The cephalic vein was catheterised following aseptic preparation, and Ringer’s acetate solution (Fresenius Kabi; Sweden) was administered intravenously (IV) at a rate of 5 ml/kg/h. Dissociative anaesthesia was induced with 5 mg/kg ketamine (Ketaminol Vet; Intervet) injected into the lumbosacral muscles 5–10 mins before initiating the surgery. All cats were placed in dorsal recumbency. Supplemental oxygen was supplied using a t-piece breathing system (FGF 2 l/min) and a tight-fitting face mask. Intraoperative non-invasive monitoring included arterial pressure (Cardell Veterinary Monitor; Sharn Veterinary) by placing the cuff distal to the right carpus, oxygen saturation, pulse rate (Pulse Oximeter 9847 V; Nonin), rectal temperature, respiratory rate, muscle tonus and pupillary reflex. If signs of insufficient anaesthetic depth were suspected, such as mean arterial pressure (MAP) >120 mmHg for >1 min, elevated HR, eye blinking or body movement, a 1 mg/kg propofol (Vetofol Vet 10 mg/ml; VM Pharma AB) IV bolus was administered.

Before surgery, cats were randomly divided into three groups (n = 25 per group) to receive one of the following treatments as preoperative incisional local anaesthesia administered subcutaneously: control group (CG) – 0.3 ml/kg sodium chloride 0.9%; group GL − 1.5 mg/kg lidocaine (Xylocain 10 mg/ml; AstraZeneca); group GLB − 1 mg/kg lidocaine combined with 1 mg/kg bupivacaine (Marcain 2.5 mg/ml; AstraZeneca). The local anaesthesia or placebo were given approximately 15 mins before the initiation of the surgical procedure. The anaesthetic procedure and monitoring, as well as assessing the recovery, were performed by a clinician unaware of the treatment groups.

OHE was performed by senior veterinary students under the supervision of a surgeon instructor, also unaware of the treatment groups. Briefly, a 6–7 cm long ventral midline incision was made through the skin, subcutaneous tissues and linea alba. The two-clamp technique was used in the OHE. The excision of both ovaries was performed after ligation of the mesovarum with 3-0 polyglactin 910 suture. The linea alba and subcutaneous tissues were closed with 3-0 polydioxanone in a simple continuous pattern. The subcutaneous tissue was closed with 4-0 polyglecaprone 25. The skin incision was closed with simple interrupted sutures of size 3-0 monofilament nylon. The surgery time was considered concluded at the end of the skin suturing. During recovery, all of the cats were monitored for postoperative pain, side effects (eg, seizures, nausea and prolonged sedation) and given 0.05 mg/kg atipamezole (Atipam vet; Dechra Veterinary Products). All cats were sent home in the same day when fully recovered from anaesthesia and without signs of pain. The owners were asked to bring the cats for a recheck 2 weeks later for surgical site complications at the time of suture removal.

Data analysis

All statistical analysis was conducted with GraphPad Prism Software Version 7. The age, weight and surgical time were compared between groups using one-way ANOVA. Furthermore, the mean values for HR and arterial pressure were measured during surgery at six different time points: surgical preparation (T0); midline incision (TI); ligation and excision of the first ovary (TO1); the second ovary (TO2) and the uterine body (TU); and suturing of midline (TS). All physiological parameters were compared between groups over time using two-way ANOVA and Bonferroni post-tests. Data are presented as mean ± SD. Differences between mean ± SD were considered significant at P <0.05.

Results

A total of 75 cats of different breeds were subjected to statistical analysis. All cats were included in the study. No adverse events or reactions were observed. Groups did not differ with regard to age, body weight and surgical time (Table 1). Respiratory rate was similar in all groups (20 ± 7 for group CG, 22 ± 11 for group GL, 22 ± 9 for group GLB; P >0.05). No differences were observed in temperature, oxygen saturation and electrocardiography during the surgical procedures. The majority of the cats (60%) included in the control group received a supplemental bolus of propofol during surgery, owing to increase of muscle tonus and pupillary reflex. However, only 43% and 44% of the cats included in the GL and GLB groups, respectively, were given a supplemental bolus. The remaining cats maintained an adequate plane of surgical anaesthesia, and anaesthetic depth was constantly monitored until the end of the surgery.

Table 1

Demographic data, body weight and surgery time in cats undergoing ovariohysterectomy (three treatment groups, n = 25 cats/group)

	Groups
Variable	CG	GL	GLB
Age (months)	19 ± 15 (6–64)	22 ± 16 (4–73)	21 ± 16 (5–73)
Weight (kg)	2.99 ± 0.49 (2.24–4.25)	2.97 ± 0.49 (2.30–4.16)	2.98 ± 0.46 (2.10–4.00)
Surgical time (mins)	66 ± 14 (40–98)	66 ± 12 (40–88)	75 ± 15 (48–97)

Data are mean ± SD (range). No significant difference (P >0.05) between groups

CG = control group, 0.3 ml/kg saline 0.9% subcutaneously (SC); GL = 1.5 mg/kg lidocaine SC; GLB = 1 mg/kg lidocaine combined with 1 mg/kg bupivacaine SC

HR was higher in the control group (CP) at the time points TO2 (excision of the second ovary) and TU (excision of the uterine body), and this difference was statistically significant in both groups GL and GLP when compared with CP (Figure 1a). MAP was stable in both groups GL and GLB during surgery, in contrast it tends to increase in the control group until the time point TO2, where a significant difference was seen (Figure 1b). HR and MAP were not statistically different between treatment groups GL and GLB. All animals were returned to their owners within 6 h of recovery without complications. In total 44/75 cats returned to the University Animal Hospital for skin suture removal 2 weeks after surgery. By then, only 5% of cats were reported to have minor surgical site swelling and no differences were observed between treatment groups.

Figure 1

Intraoperative variation in the (a) mean heart rate and (b) mean arterial pressure. Three treatment groups (n = 25 cats/group). Data are mean ± SD. *P <0.05. bpm = beats per minute; CG = control group, 0.3 ml/kg saline 0.9% SC; GL = 1.5 mg/kg lidocaine SC; GLB = 1 mg/kg lidocaine combined with 1 mg/kg bupivacaine SC; T0 = preparation; TI = midline incision; TO1 = ligation and excision of the first ovary; TO2 = the second ovary; TU = the uterine body; TS = suturing of abdominal muscular layers

Discussion

Local anaesthetics such as lidocaine and bupivacaine are extensively used as analgesics in veterinary medicine. These drugs produce complete blockade of the sensory nerve and when combined with general anaesthesia have significant perioperative analgesic benefits and an anaesthetic-sparing effect.¹² Lidocaine has a relatively faster onset and shorter duration of action, whereas bupivacaine has a slower onset but a longer period of action.²¹ When both drugs are combined, the required doses are lower, and allow a faster onset of action and prolonged effect.²²

The use of incisional and intraperitoneal local anaesthesia during OHE in cats and dogs have shown mixed results regarding the additional gain of intra- or postoperative analgesia. In one study, the use of lidocaine in the incision site and mesovarium has been demonstrated to reduce the requirement for administration of supplementary anaesthesia during OHE in cats.¹⁸ On the contrary, according to Bubalo et al,²³ no evidence of an additional intraoperative analgesic effect of lidocaine in the mesovarium was demonstrated in dogs. Regarding the use of intraperitoneal bupivacaine, a study by Campagnol et al¹⁹ showed beneficial analgesic effects only in postoperative pain in dogs undergoing OHE. The results of this study also suggest no benefit for preincisional infiltration of bupivacaine. A similar finding was reported in feline OHE.¹⁷ However, these results are in contrast to another study, which used a higher dose and volume of bupivacaine for incisional infiltration, which included both subcutaneous and intramuscular infiltration.²⁴ Lidocaine’s short period of action can be insufficient when used in the context of a veterinary student programme of feline spaying, which often incurs longer surgical time, and rather basic anaesthetic and analgesic monitoring. Hence, the use of lidocaine combined with bupivacaine would prolong its analgesic effect and improve animal welfare. To the best of our knowledge, no studies evaluating the intraoperative analgesic effect of incisional lidocaine alone or combined with bupivacaine during general anaesthesia have been described in cats undergoing OHE.

The OHEs in our study were performed by fourth-year veterinary students, and thus the average operative time of 70 mins was longer than in previous studies, which ranged from 12–60 mins.^17,25–29 Nevertheless, the surgery times (between 40 and 98 mins) were shorter than the duration of action of the lidocaine (60–120 mins) and bupivacaine (240–360 mins).

The correlation between physiological parameters (eg, HR and arterial pressure) and intraoperative nociception is commonly used. When the sympathoadrenal system is triggered by a nociceptive stimulus, it leads to an increase in HR, cardiac output and blood pressure.³⁰ Therefore, increased HR and arterial pressure can represent a response to nociceptive stimulus following the start of surgery.^31,32 Our study demonstrated that incisional lidocaine alone or combined with bupivacaine provides beneficial intraoperative analgesia in cats where dissociative anaesthesia was used. The incisional local anaesthesia prior to pain onset had blocked the sensory response in the subcutaneous tissue and abdominal muscle from stretching and manipulation, which partly contributes to the overall intraoperative noxious response. After skin incision, the control group showed a tendency to increased HR and MAP (19% and 22%, respectively) and remained higher when compared with the treatment groups (GL and GLB). Despite the delay in onset of action of bupivacaine (20–30 mins), no difference in the nociceptive response was observed between treatment groups (GL and GLB) during skin incision.

The combination of medetomidine, ketamine and buprenorphine has been shown to maintain an adequate plane of surgical anaesthesia in feline OHE, but may require anaesthesia supplementation.³³ In our study, the prevalence of rescue analgesia by supplemental bolus of propofol was similar between treatment groups (GL 43% and GLB 44%), and lower when compared with the control group (60%). Thus, it is likely the depth of anaesthesia in the control group was not the same as in the treatment groups, which possibly had more fluctuations and increased the noxious response during the ligation and excision of the second ovary and uterine body. Even though the systemic contribution of the local anaesthetics on the anaesthetic-sparing effect and on blood pressure cannot be excluded, it is unlikely the small amount of lidocaine and bupivacaine given subcutaneously had reached high enough plasma levels to provide systemic analgesic effects and lower blood pressure.

In this study, we opted to exclude the injection of local anaesthesia in the mesovarium to have a more specific evaluation of the incisional analgesia and to avoid the risks of inadvertent intravenous bupivacaine injection. Therefore, the nociceptive stimulus arising from the traction on the ovaries was present in all groups.

The surgical dissection can contribute to the formation of a wound haematoma in the incision line. Its risk can increase when lidocaine is injected subcutaneously, as it acts as a local vasodilator.³⁴ However, its formation was not evident in this study. The postoperative complications rate remained low (5%) and the same in all groups.

Conclusions

The addition of local anaesthesia in both treatment groups (GL and GLB) to the anaesthetic protocol improved the intraoperative analgesia in cats undergoing OHE. The control group required more rescue analgesia, and exhibited higher HRs and MAPs. However, the incisional block with lidocaine or a mixture of lidocaine with bupivacaine produced a similar decrease in nociceptive responses.

Despite the similar analgesic effect observed in both treatment groups, the combination of lidocaine and bupivacaine should be considered as a reliable alternative to lidocaine alone in linear blocks, as it reduces the required doses, and it has a faster onset of action and prolonged effect when compared either with lidocaine or bupivacaine alone.

Footnotes

Acknowledgements

We are grateful to all cats, nurses and students that participated in this study. Special thanks to Anja Temdahl Sundström, anaesthesia nurse, University Animal Hospital, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, for her dedication in reducing the perioperative pain of the cats and for her commitment in gathering the cats included in the study.

Accepted: 6 September 2017

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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Evaluation of intraoperative analgesia provided by incisional lidocaine and bupivacaine in cats undergoing ovariohysterectomy

Abstract

Objectives

Methods

Results

Conclusions and relevance

Introduction

Materials and methods

Animals

Anaesthesia and surgery

Data analysis

Results

Discussion

Conclusions

Footnotes

Acknowledgements

Conflict of interest

Funding

References