Methods

This study was approved by the institution’s Veterinary Clinical Studies Committee (protocol No. 031220-03) and follows Animal Research: Reporting of In Vivo Experiments guidelines.⁶ Cats undergoing OVH as part of surgical exercises for veterinary students between September and November 2020 were included. Cats were excluded from the study if the American Society of Anesthesiologists physical status was more than 2, if a different surgical procedure was performed in addition to OVH, or if the cats became hyperthermic during anesthesia (prior to the administration of the study agents). Physical status was assigned based on physical examination and bloodwork, including hematocrit, total plasma proteins, blood glucose, and urea concentrations.

All cats were admitted to our institution the day prior to their surgery and were housed individually. Each cat received maropitant (Cerenia; Zoetis) 8 mg total per os (PO), robenacoxib (Onsior; Elanco) 6 mg total PO, and cefovecin sodium (Convenia; Zoetis) 8 mg/kg SC the afternoon prior to the procedure. Food, but not water, was withheld starting the evening prior to anesthesia. Cats were anesthetized and operated between 7 am and 12 noon, or between 1 and 5 pm.

All cats received dexmedetomidine (Dexdomitor; Zoetis) 20 μg/kg and morphine (West-Ward) 0.1 mg/kg intramuscularly (IM). Approximately 15 minutes later, an intravenous catheter was placed. Ketamine (Ketathesia; Henry Schein Animal Health) 5 mg/kg IM was administered to cats that were insufficiently sedated for catheterization. Anesthesia was induced with propofol (Sagent Pharmaceuticals), administered until intubation was possible, and anesthesia was maintained with isoflurane in oxygen (1 to 2 L/min) using a circular rebreathing system. Cats were placed in dorsal recumbency, and the abdomen was clipped and scrubbed in the induction area, adjacent to the surgical room. No heating devices were used during this period. Cats were then transferred to the surgical table and placed in dorsal recumbency over a circulating warm water blanket (T/PUMP Heat Therapy Pump; Gaymar Industries) and a disposable, impermeable underpad. The warm-water blanket was set at 42 °C. A midline laparotomy was performed. Monitoring included continuous electrocardiogram, pulse oximetry, capnography, esophageal temperature, and oscillometric blood pressure (every 2 minutes). Lactated Ringer solution was administered at 5 mL/kg/h intravenously (IV) to all cats during anesthesia. If the esophageal temperature decreased to less than 36 °C, warm saline bags were placed around the cat’s neck and shoulders. All cats breathed spontaneously during the procedure. After surgery was completed, the cats were vaccinated against rabies, and isoflurane was discontinued. Cats were extubated when the swallowing reflex was observed. In cats that were difficult to restrain manually or appeared aggressive at recovery, dexmedetomidine 1 μg/kg was administered IV. If, on the contrary, a cat appeared overly sedated after extubation, atipamezole (Antisedan; Zoetis) 0.1 mg/kg was administered IM.

Results

Two cats became hyperthermic during anesthesia and were excluded prior to randomization for opioid treatment. A total of 94 cats were randomized to receive either buprenorphine or morphine upon recovery from anesthesia (47 in each group). Demographic data, time and duration of anesthesia, and administration of ketamine, dexmedetomidine, and atipamezole are summarized (Table 1). Cats receiving morphine were older and heavier than those receiving buprenorphine.

Preoperative, intraoperative, and postoperative body temperatures were evaluated (Figure 1). Overall, there were significant effects of time (P < 0.001) and treatment (P = 0.033) on body temperature, with cats receiving buprenorphine having greater values than those receiving morphine. The point prevalence of hyperthermia for cats receiving buprenorphine and morphine was 55% (26/47) and 28% (13/46) at 2 hours, 44% (21/47) and 13% (6/46) at 4 hours, and 62% (27/43) and 47% (21/44) at 16 to 20 hours after extubation.

View Full Size

Individual-value plots of rectal temperature prior to anesthesia (T0), mean esophageal temperatures throughout anesthesia (T1), and rectal temperature at extubation (T2) and then at 2 (T3), 4 (T4), and 16 to 20 (T5) hours after extubation for 94 cats undergoing ovariohysterectomy and randomly assigned to receive 1 subcutaneous dose of either buprenorphine (0.24 mg/kg; n = 47; filled circles) or morphine (0.1 mg/kg; n = 47; open circles) immediately after extubation (dotted vertical Treatment line) between September and November 2020. For each plot, the horizontal line between the whiskers represents the mean, the whiskers represent the SD, and each circle represents a result for one cat.

Citation: American Journal of Veterinary Research 83, 6; 10.2460/ajvr.21.11.0183

• Download Figure
• Download figure as PowerPoint slide

There were no differences in the GCMPS-Feline score between treatment groups (P = 0.244) or over time (P = 0.931). Four hours after recovery, scores were 0 (range, 0 to 7) for cats receiving buprenorphine and 0 (range, 0 to 6) for cats receiving morphine. Four cats receiving buprenorphine and two receiving morphine scored ≥ 5/20 at this time point and were subsequently removed from the study. At 16 to 20 hours, cats receiving buprenorphine scored 0 (range, 0 to 6) and those receiving morphine scored 0 (range, 0 to 12). One cat in the buprenorphine group and 4 in the morphine group scored ≥ 5/20 at 16 to 20 hours. All cats were discharged 24 hours after surgery.

Discussion

The main findings from this study are that postoperative temperature and the point prevalence of hyperthermia were greater with this formulation and dose of buprenorphine than with morphine 0.1 mg/kg, and that no differences were found on postoperative pain scores up to 20 hours after recovery from anesthesia.

Hyperthermia secondary to opioid administration in cats has long been described with several agents, including buprenorphine.^3,10–12 In our study we evaluated buprenorphine at a concentration and dose that offers analgesia for up to 24 hours after a single SC injection.⁴ A recent retrospective study suggested that hyperthermia occurred more often and lasted longer after that formulation of buprenorphine was used compared with a group of cats receiving morphine.⁵ Our prospective study confirms that hyperthermia was found at a greater rate when buprenorphine was used compared with morphine.

Higher rectal temperatures and a greater occurrence of hyperthermia were recorded when buprenorphine was used. Of particular importance, a high incidence of hyperthermia was observed with both agents almost 24 hours after SC administration. Given that some animals were hyperthermic prior to anesthesia and surgery, presumably from the stress associated with hospitalization and examinations, we surmise that the causes for these elevated temperatures are multifactorial. However, at every time point after administration of opioids, temperature was higher in those cats receiving buprenorphine, suggesting that agent selection played a decisive role in temperature upregulation.

Following an initial increase in temperature observed 2 hours postoperatively, a small decrease was registered for both groups at 4 hours after recovery from anesthesia. However, higher temperatures and a greater point prevalence of hyperthermia were measured again 12 to 16 hours later. Our study does not allow us to investigate the causes for this biphasic change in postoperative temperature. It is possible that stress-induced increases in temperature had more impact the morning after surgery, when residual sedative effects from anesthesia had dissipated.

In our study we defined hyperthermia as a rectal temperature > 39.2 °C, based on previous reports.^13,14 It is unclear whether this level of hyperthermia, or this duration, could result in any clinically significant consequences to cats; all cats in this study were discharged within 24 hours from recovery of anesthesia. Although this level of hyperthermia may not be considered clinically consequential, it could impede or delay the diagnosis of fever, which may result from postoperative infections.

Postoperative discomfort was evaluated with the GCMPS, which was measured at 4 and 16 to 20 hours after recovery from anesthesia. No differences were found between groups, nor within groups, over time. The expected duration of analgesia provided by this dose of buprenorphine (24 hours) is substantially longer than that expected from morphine—an agent with a half-life of 90 minutes after twice the dose used in this study¹⁵—which led us to hypothesize that lower pain scores would be associated with buprenorphine 16 to 20 hours after administration. It is possible that the analgesic effects provided by robenacoxib were sufficient to mask any differences between both opioid agents. Overall, scores were low and only few cats required rescue analgesia.

There are limitations to this study. As mentioned previously, our data do not allow us to examine the contribution of other factors to hyperthermia, such as stress, vaccination, or the contribution of preoperative morphine administered to all cats. However, given the similar management between groups, we do not expect that those effects would have introduced a bias toward one treatment group. Hyperthermia associated with the vaccine used is reported as a very rare event, and hence, unlikely to have contributed to our results in a substantial manner.¹⁶ There were differences between groups in terms of age and weight. We cannot comment on whether these differences could have introduced a bias in the results. A pain score was only assessed shortly after surgery and the next morning. Unfortunately, we were not able to obtain pain scores during the evening of surgery.

In summary, administration of buprenorphine 0.24 mg/kg SC to cats following OVH resulted in higher temperatures and a greater point prevalence of hyperthermia (> 39.2 °C) than morphine 0.1 mg/kg SC during the first 20 postoperative hours. We found no advantages to using buprenorphine with regard to postoperative pain scores after OVH in cats compared with morphine.