Randomised clinical trial comparing the perioperative analgesic efficacy of oral tramadol and intramuscular tramadol in cats

Abstract

Objectives

The aim of this study was to evaluate the analgesic efficacy of oral tramadol in cats undergoing ovariohysterectomy.

Methods

Twenty-four female domestic cats, American Society of Anesthesiologists class I, aged 4–24 months, were included in this positive controlled, randomised, blinded clinical trial. Cats admitted for ovariohysterectomy were allocated to group oral tramadol (GOT, n = 12) or group intramuscular tramadol (GIMT, n = 12). In GOT, tramadol (6 mg/kg) was given orally 60 mins, and saline was given intramuscularly 30 mins, before induction of anaesthesia. In GIMT, granulated sugar in capsules was given orally 60 mins and tramadol (4 mg/kg) intramuscularly 30 mins before induction of anaesthesia. In both groups, dexmedetomidine (0.007 mg/kg) was given intramuscularly 30 mins before induction of anaesthesia with intravenous propofol. Anaesthesia was maintained with isoflurane in oxygen, and atipamezole (0.037 mg/kg) was given intramuscularly 10 mins after extubation. The UNESP-Botucatu multidimensional composite scale was used to conduct pain assessments before premedication and at 20, 60, 120, 240 and 360 mins post-extubation or until rescue analgesia was given. To compare groups, the 60 min postoperative pain scores and the highest postoperative pain scores were analysed via a two-tailed Mann–Whitney test, and the incidences of rescue analgesia were analysed via a Fisher’s exact test; P <0.05.

Results

There was no significant difference between groups for the 60 min (P = 0.68) pain scores. The highest postoperative pain score was higher for GIMT compared with GOT (P = 0.04). Only two cats required rescue analgesia, both from GIMT. The incidence of rescue analgesia was not significantly different between groups (P = 0.46).

Conclusions and relevance

In the present study, preoperative administration of oral tramadol at 6 mg/kg to cats provided adequate analgesia for 6 h following ovariohysterectomy surgery.

Introduction

Tramadol is an atypical opioid that is also a serotoninergic and noradrenergic reuptake inhibitor (SNRI) (1). In humans, the primary tramadol metabolites are O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N, O-didesmethyltramadol (M5). M1 has a higher affinity for μ-opioid receptors than the parental tramadol and is mainly responsible for the opioid-derived analgesic effects. ¹

Because of its pharmacological properties, tramadol has become one of the most dispensed analgesic drugs to treat moderate to severe pain in human medicine. ¹ In small animal veterinary medicine, tramadol was used with mixed successes in the dog.^2–9 The reduced analgesic efficacy of tramadol in dogs can be attributed to the rapid elimination of the parent compound (tramadol), the low capacity to produce the M1 metabolite and its rapid degradation, some breed and individual polymorphism of P450 isoenzyme, and its pharmacokinetic profile not being supportive of clinical utility.^8,10–13

In cats, the pharmacokinetic profile of per os (PO, 5.2 mg/kg) and intravenous (IV, 2 mg/kg) tramadol has been studied. The PO bioavailability (93% ± 7%) was higher compared with dogs (65%) and humans (68%), and the elimination half-life (3.4 h) was markedly longer than dogs (1.7 h) but shorter than humans (5.5 h). ¹⁴ The maximum plasma concentrations (C_max) of the M1 metabolite in cats (PO: 655 ng/ml, IV: 366 ng/ml) were higher than the reported human C_max at therapeutic steady-state (11 ng/ml). However, there was significant individual variation in C_max (484–1663 ng/ml) of M1 after PO administration, potentially due to difference in absorption rate and gastrointestinal transit time.^10,14 The terminal half-life of M1 was 289 and 261 mins after PO and IV tramadol administration, respectively. ¹⁴ This pharmacokinetic profile of PO tramadol is consistent with the potential for clinical relevance, and the drug should be tested for its analgesic efficacy in a clinical setting.

Dosages for this study were selected based on dosages reported in previous studies. Lower doses of subcutaneous (SC) tramadol of 1 mg/kg and 2 mg/kg in cats resulted in a minimal effect on the nociceptive threshold and in 50% of the cats requiring rescue analgesia following ovariohysterectomy, respectively.^15,16 However, intramuscular (IM) tramadol at 2 and 4 mg/kg was more efficacious to treat post-ovariohysterectomy pain, with only two out of 14 and none out of 14 cats requiring rescue analgesia, respectively. ¹⁷ The same doses given PO appeared necessary for inducing thermal antinociception in cats and simulations predicted that 4 mg/kg PO q6h would maintain analgesia close to the maximal effect. ¹⁸ Administered intravenously, tramadol (2 mg/kg) produced sufficient postoperative analgesia in male cats following gonadectomy for up to 6 h. ¹⁹

The purpose of this study was to evaluate the clinical analgesic efficacy of PO tramadol in cats undergoing ovariohysterectomy by use of a validated multidimensional composite pain scale. IM tramadol was used as a positive control group. Knowing that oral bioavailability of tramadol is 93%, the null hypothesis was that PO tramadol (6 mg/kg) would provide analgesic efficacy not different to IM tramadol (4 mg/kg) in the postoperative period following ovariohysterectomy.

Materials and methods

The study was designed as a controlled randomised blinded clinical trial and was approved by the animal ethics committee of the institution where the study was performed (ethic number 1413399.2).

Animals

During an approximately 7-month period, domesticated female cats of less than 4 years of age that were referred to the University Veterinary Hospital for elective ovariohysterectomy were included in the trial after agreement and signed consent were obtained from the owners. Cats were determined healthy after obtaining a thorough history, physical examination and haematological analysis including blood urea nitrogen and glucose concentrations.

The exclusion criteria included: (1) cats that were not easily handled due to demeanour; (2) cats with abnormal physical examination; and (3) cats with abnormal haematological analysis. The criteria for removal of subjects from the study included: (1) cats with a surgery time of more than 1 h; and (2) cats that received an anaesthetics or analgesics regimen other than those described in the protocol below.

Experimental design

The cats were randomly allocated using the random function of a commercially available software package (Microsoft Excel 2010), to group oral tramadol (GOT, n = 13) or group IM tramadol (GIMT, n = 13).

At the time of study design, no data were available regarding the efficacy of oral tramadol in an acute pain setting to establish group sizes base on power calculation. Therefore, the author aimed to achieve similar group sizes to those reported in a similar study evaluating the analgesic efficacy of IM tramadol in cats undergoing ovariohysterectomy. ¹⁷

In the GOT, tramadol (6 mg/kg, Tramal, 50 mg capsule; Grunenthal GmbH) was given PO 60 mins, and in the GIMT tramadol (4 mg/kg, Tramal, 50 mg/ml; Grunenthal GmbH) was given IM 30 mins, before induction of anaesthesia. The IM dose chosen was successfully used in a previous study.17 The PO tramadol dose of 6 mg/kg used was chosen following a pilot study (n = 2), which suggested that a dose of 4 mg/kg was not providing consistently adequate post-ovariohysterectomy analgesia.

In both groups, cats were administered IM dexmedetomidine (0.007 mg/kg, Dexdomitor; Zoetis) 30 mins before induction of anesthesia. After 20 mins, a 22 G, 25 mm over-the-needle IV catheter was placed in a cephalic vein. Propofol (Provive 1%; Claris Lifesciences) was administered IV to effect (requirement reported in a previous publication), to induce anaesthesia and facilitate orotracheal intubation. ²⁰ The endotracheal tube was then connected to a paediatric rebreathing system (Small Animal Anesthesia Machine V701001; SurgiVet, Smiths Medical PM) and isoflurane (Isoflo; Abbott) in oxygen (2 l/min for the first 5 mins and 1 l/min for the remainder of the procedure) was administered to effect to maintain anaesthesia. All cats maintained spontaneous ventilation. A balanced crystalloid solution (Hartmann’s Solution for Injection; Fresenius Kabi) was administered IV at a rate of 10 ml/kg/h during anaesthesia.

A calibrated multiparametric anaesthesia monitor (Advisor Vital Signs Monitor V9203; SurgiVet, Smiths Medical PM) displayed continuous electrocardiogram, end tidal isoflurane, heart rate (HR), respiratory rate ( f_R), end tidal carbon dioxide (Pe′CO₂), and arterial haemoglobin oxygen saturation (SpO₂) data. Mean arterial blood pressure (MABP) was obtained via a non-invasive oscillometric blood pressure device (PetMAP Graphic; Ramsey Medical). The cuff used for the blood pressure measurements was placed proximal to the right metacarpal region, and its width was approximately 45% of the limb circumference. Bradycardia and hypotension were defined as an HR of less than 90 beats/min and a MABP of less than 60 mmHg, respectively.

An experienced community practice surgeon performed the ovariohysterectomy following surgical standards of the institution. Atipamezole (0.0375 mg/kg, Antisedan, Atipamezole hydrochloride 5 mg/ml; Pfizer Animal Health) was administered IM 10 mins post-endotracheal extubation. Anaesthesia time was defined as the time from the start of anaesthetic induction to the time of extubation, and surgery time was defined as the time from the primary skin incision to the placement of the last skin suture.

Blinding and drug preparation

The head clinical anaesthetist on duty prepared the premedication that was administered by the person assigned to perform the pain evaluation. To maintain blinding, each cat was administered an IM injection using a 25 G insulin needle and syringe in the lumbar region and a capsule positioned at the back of its throat before closing its mouth. For GOT, 0.08 ml/kg of NaCl 0.9% was administered IM, and 6 mg/kg of tramadol was administered through the capsule. For GIMT, 4 mg/kg of tramadol was administered IM and encapsulated granulated sugar was administered PO. To achieve appropriate tramadol dosing through PO administration, each tramadol capsule was emptied and its content weighed (A&D GH-252 scale with internal calibration, capacity in semi-micro range 101 g capacity, 0.01 mg readability). The appropriate dosage was transferred back into the capsule. For GIMT, a similar weight of granulated sugar was transferred into an emptied tramadol capsule and administered as PO control treatment.

Physiological variables monitored during general anaesthesia

During anaesthesia, cats were assessed every 5 mins for HR, ( f_R), end tidal CO₂ (EtCO₂), SpO₂, and MABP. HR and f_R were derived from the SpO₂ reading and EtCO₂ reading, respectively.

Pain assessment

The pain evaluator was unaware of the treatment that each cat received and all cats were assessed by the same trained veterinary anaesthesiologist, according to a published multidimensional composite pain scoring system validated for use in assessing postoperative pain in cats undergoing ovariohysterectomy.21

Pain assessments were performed before administration of anaesthetic premedication (baseline) and after surgery 20, 60, 120, 180, 240 and 360 mins after extubation or until rescue analgesia was administered. If at any time point the evaluation score exceeded 7 of 30, the patient was determined to be in moderate to severe pain and was given IV methadone as rescue analgesia (0.2 mg/kg, Methone; Ceva Animal Health). All cats were given SC meloxicam (0.2 mg/kg, Metacam, meloxicam 5 mg/ml; Boehringer Ingelheim), following the last pain score evaluation or if rescue analgesia was dispensed.

All blood pressures recorded, before premedication and at each pain score evaluation time point, were measured with the same veterinary-specific handheld oscillometric blood pressure measurement device used during the period of general anaesthesia. The width of the blood pressure cuff selected for each cat was measured to comply with manufacturer recommendations (cuff width was 42–50% of the limb circumference) and was placed proximal to the metacarpal region. Systolic arterial blood pressure measurements were used in the scoring system. Blood pressure measurements were performed in triplicate or until three consecutive similar measurements were obtained (ie, systolic arterial blood pressures within 15 mmHg of each other). The HR given by the blood pressure measurement device had to match the auscultated HR for the blood pressure measurement to be retained.

From the pain assessment results, four scores were defined: (1) the preoperative score was the baseline pain evaluation score determined before premedication and was analysed to detect any baseline difference between the two groups and to detect any abnormal behaviour that may have interfered with the scoring system; (2) the rescue analgesia score was 0 if no rescue analgesia was administered during the postoperative 360 min period, and 1 if rescue analgesia was administered; (3) the 60 min point evaluation score was the postoperative pain evaluation score at 60 mins post-extubation; and (4) the highest postoperative pain score assigned to a cat during the 360 min postoperative period.

Postoperative dysphoria

At each pain scoring time point and before interacting with the cat, a dysphoria score was subjectively attributed to each cat. The dysphoria score ranged from 0–3 with 0 being no dysphoria, 1 being mild agitation (increased activity compared with preoperative observation); 2 being marked agitation (animal frequently moving and changing position) but not requiring sedation; and 3 being a restless cat requiring sedation. For each cat, the highest dysphoria score was reported. When suspicions of possible hyperthermia were raised (eg, agitated cats, cats feeling warm), the postoperative rectal temperatures were measured at the discretion of the anaesthetist at the 20 min pain score assessment using a digital thermometer (flex-tip digital thermometer; Apex). Any postoperative rectal temperatures above 39°C were reported.

Statistical analysis

Data analysis, comparisons between GOT and GIMT and graphical representations were performed by using a commercially available software package (IBM SPSS Statistics, version 20; International Business Machines Corp and GraphPad Prism 6 for Windows; GraphPad Software). The Shapiro–Wilk test was used to test for normality of residuals. Comparison of age, weight, anaesthesia and surgery time were analysed with a two-tailed t-test. The preoperative score, 60 min scores, highest postoperative pain score and highest dysphoria scores were analysed via a two-tailed Mann–Whitney exact test. The rescue analgesia scores were analysed via Fisher’s exact test. The highest dysphoria scores were also used to compare cats of less than 6 months old and cats of more than 6 months old within each group. Results are reported as mean ± SD or median (range). Values of P <0.05 were deemed significant.

Results

Animals, anaesthesia time and surgery time

Of the 26 female cats that were included in this study, one cat was excluded for receiving alfaxalone rather than propofol as an induction agent, and one cat was excluded for not receiving dexmedetomidine as part of the premedication. No cats died or were euthanased during the study. Mean ± SD weight was 2.3 ± 0.5 kg for the 12 GOT cats (12 domestic shorthair cats) and 2.8 ± 0.5 kg for the 12 GIMT cats (nine domestic shorthair, two domestic medium hair and one Ragdoll cat). The cats’ ages were not significantly (P = 0.46) different between GOT (37 weeks; 17–102 weeks) and GIMT (28 weeks; 22–102 weeks). Anaesthesia time was not significantly different (P = 0.34) between GOT (56 ± 16 mins) and GIMT (64 ± 24 mins), and mean ± SD surgery times were 24 ± 11 and 21 ± 12 mins for GOT and GIMT, respectively (P = 0.62).

Physiological variables monitored during general anaesthesia

Neither bradycardia nor hypotension was identified in any of the cats. None of the cats developed apnoea, and the EtCO₂ remained inferior or equal to 50 mmHg in all cats throughout the anaesthesia. Arterial oxygen saturation of haemoglobin remained > 95% in all cats.

Pre- and postoperative pain assessments

Pre- and postoperative pain scores are reported in Table 1. There was no significant difference between GOT and GIMT for the pre-operative (P = 0.68) and 60 min (P = 0.68) pain scores. The 20 min scores were not taken into consideration for the statistical analysis of the highest pain score, since postoperative dysphoria encountered in some cats prevented a complete collection of all data (ie, systolic arterial blood pressure in two cats from GOT) and was potentially affecting the pain scores. The highest postoperative pain score was higher for GIMT (5; 1–12) compared with GOT (4; 1–6) (P = 0.04; Figure 1).

Table 1.

Summary of pain evaluation scores for both GOT and GIMT. Twenty-four cats undergoing ovariohysterectomy received intramuscular tramadol (GIMT, 4 mg/kg, n = 12) or oral tramadol (GOT, 6 mg/kg, n = 12) for perioperative analgesia

Group	Preoperative evaluation		Evaluation at 20 mins		Evaluation at 60 mins		Evaluation at 120 mins		Evaluation at 240 mins		Evaluation at 360 mins
	n	Scoremedian (range)	n	Scoremedian (range)	n	Scoremedian (range)	n	Scoremedian (range)	n	Scoremedian (range)	n	Scoremedian (range)
GOT	12	0 (0–1)	12	3.5 (0–6)	12	3 (0–6)	12	2.5 (0–6)	12	2.5 (0–5)	12	1.5 (0–4)
GIMT	12	1 (0–1)	12	3 (0–6)	12	3 (1–12)	11	5 (0–9)	10	3.5 (0–6)	10	2 (0–7)

n = number of animals evaluated; Score = pain scores (out of 28) preoperatively (preoperative evaluation score) and during the postoperative period at 20, 60, 120, 240 and 360 mins after extubation or until rescue analgesia was given. The pain scores were obtained using a validated pain scale.21 If the pain evaluation score was greater than 7, the cat was evaluated as being moderately to severely painful, and rescue analgesia was administered. If a cat received rescue analgesia, the subsequent pain scores were not taken into consideration for the reporting and calculation of medians and ranges. The 20 min scores need to be interpreted with caution as postoperative dysphoria encountered in some cats prevented the appropriate collection of all data (ie, systolic arterial blood pressure in two cats from GOT) and was potentially affecting the pain scores

Figure 1.

Box and whisker plots of the highest postoperative (a) and the 60 min (b) pain scores of 24 cats undergoing ovariohysterectomy receiving intramuscular tramadol (GIMT, 4 mg/kg, n = 12) or oral tramadol (GOT, 6 mg/kg, n = 12) for perioperative analgesia. The box indicates the interquartile range (25th to 75th percentile), the black line in the box indicates the median and the whiskers indicate the range. Pain scores were obtained by use of a validated multidimensional composite scale.21 Outliers > 1.5 times the interquartile range (circles) are shown

No cat from GOT required rescue analgesia. In GIMT, rescue analgesia was administered to one cat after the 60 min pain score and to another after the 120 min pain score. The incidence of rescue analgesia was not significantly different between the two groups (P = 0.46).

Postoperative dysphoria

The highest dysphoria scores occurred for most cats (n = 4 for GMIT; n = 6 for GOT) at the 20 min pain evaluation. For one cat in GIMT, the highest dysphoria score (1) occurred at 240 mins. All the other cats scored 0 throughout the evaluation period.

The median highest dysphoria score for GIMT (0 [0–1]) was not significantly different (P = 0.09) compared with GOT (0.5 [0–2]). No cat required additional sedation in recovery. Within the GIMT, the median highest dysphoria score of cats aged less than 6 months old (n = 6, 0.5 [0–1]) was not significantly different (P = 0.39) than the one of cats older than 6 months (n = 6, 0 [0–1]). However, within GOT, the median highest dysphoria score of cats aged 6 months old or less (n = 5, 2 [1–2]) was significantly higher (P = 0.018) than the one of cats older than 6 months (n = 7, 0 [0–1]). Two cats from GIMT (both 26 weeks old) and two cats from GOT (26 and 35 weeks old) developed rectal temperature between 39.5°C and 39.9°C. The dysphoria scores for those cats were 0 and 1 for the GIMT cats, 0 for the 35-week-old GOT cat and 2 for the 26-week-old GOT cat.

Other observations

Vomiting was observed in two cats from GIMT and one cat from GOT post-IM injection, and two cats from GIMT and one from GOT developed an occasional facial itch during the first 120 mins postoperatively. Signs of facial itch included the animal pawing at its face and licking its lips.

Discussion

The present study, designed to assess the analgesic efficacy of oral tramadol in cats, confirmed the null hypothesis that PO tramadol (6 mg/kg) provided at least equivalent analgesic efficacy as IM tramadol (4 mg/kg). Because ovariohysterectomy is known to be a painful procedure requiring analgesia, a negative control group was not included in the study design for ethical reasons. ²² The IM dose chosen was successfully used in a previous study and provided adequate postoperative analgesia for 6 h in 83% of cats (positive control group) in the current study. ¹⁷ In comparison, in a 2019 study, a tramadol dose of 2 mg/kg SC only provided adequate postoperative analgesia to approximately 71% (5/7) of cats undergoing ovariohysterectomy. ²³ The PO tramadol dose of 6 mg/kg used was chosen following a pilot study (n = 2), which suggested that a dose of 4 mg/kg did not provide adequate post-ovariohysterectomy analgesia in all cats. Because of the high oral bioavailability (93 ± 7%), it is not surprising to see that the 6 mg/kg PO tramadol used in this study achieved similarly adequate analgesic effects to the reported 4 mg/kg IM regimen.14 The results are also consistent with a study indicating that the thermal threshold was significantly higher than the baseline value from 40 to 360 mins after the cats were administered tramadol at 3 mg/kg PO.19

All the cats involved in this study were client-owned and representative of the domestic population. Most were young domestic shorthair or medium hair cats; however, one purebred cat was also included. There were no notable differences in temperament. The level of sedation following premedication was adequate in both groups, allowing placement of IV catheters in all cats without any further administration of sedative drugs. Preoperative agitation and/or dysphoria were not observed in either group; however, three cats vomited post-IM injection. Because vomiting was present in both groups after the IM administration of dexmedetomidine, it is likely that vomiting was a side effect of the dexmedetomidine administration, and the author does not believe it would have affected the blinding of the study.

Oral administration of drugs can allow owners to administer medications to their pet themselves, reducing the necessity for prolonged hospitalisation. Tramadol has a bitter taste that is known to induce salivation and vomiting in cats. In preliminary work, the author intended to disguise the taste of tramadol tablets using wet cat food, tuna, honey and other types of food without success. Tramadol capsules, however, were easy to administer, and no salivation or vomiting were seen shortly following the PO administration. Water was not used to ensure oesophageal clearance.

The preparation of the capsules to the correct dosage was time-consuming but feasible and should be considered as a ‘take-home’ or prescription medication option.

Although unlikely to affect the postoperative pain scores, the fluid rate administered (10 ml/kg/h) can be considered excessive and an initial fluid rate of around 3 ml/kg/h would have been more appropriate. ²⁴ The physiological data collected during anaesthesia indicated that neither PO tramadol nor IM tramadol had severe and deleterious effects on the recorded vital physiological functions, and both could be used for premedication prior to general anaesthesia.

The present study used a validated multidimensional composite pain scale for assessing postoperative pain in cats undergoing ovariohysterectomy. ²¹ However, the evaluation of the four domains included in the scale (ie, psychomotor change, protection of wound area, physiological variables, and vocal expression of pain) are also behaviours exhibited with dysphoria, resulting in artificially elevated pain scores. At the 20 min evaluation scores, a third of the GIMT cats and half of the GOT cats presented some level of dysphoria. In consequence, the 20 min scores were not analysed further and were not taken into consideration for the statistical analysis of the highest pain score.

The higher incidence, and the increased duration of dysphoria encountered in the present study compared with previous similar studies evaluating different opioids, suggest that dysphoria may be a side effect of tramadol rather than isoflurane.^25,26 The dosages of tramadol IM and PO were selected to minimise the chance of requiring rescue analgesia and, in consequence, were relatively high. By increasing the PO dose so that it was efficacious in 100% of the cats enrolled, the incidence of side effects was also likely increased. Although the side effects encountered were limited to dysphoria not necessitating sedation, their relatively high incidence may prompt further dose-finding studies, especially in younger cats. The author would emphasise the importance of tailoring analgesia to suit the individual cat’s requirements, as considerable variations in individual response to opioids and in C_max of the M1 metabolite of tramadol have been reported in this species.^14,27,28

Atipamezole has been shown to not significantly affect the postoperative pain scores in cats after ovariohysterectomy and was administered (at the licensed dose for cats in the country where the study took place) to reverse residual analgesic effects from the preoperative administration of dexmedetomidine. ²⁹ However, the author cannot exclude some residual analgesia from the dexmedetomidine.

The pure µ opioid agonist methadone was chosen as a rescue analgesic as it is effective to treat pain resulting from ovariohysterectomy in cats. ²⁵ However, methadone is also an SNRI and should be used with caution in patients that have already received another SNRI like tramadol.^30–32

As previously mentioned, no data were available to establish group sizes based on power calculation, and the author aimed to achieve similar group size to that used in a similar study. ¹⁷ The data acquired in the present study can be used to calculate that 122 cats in each group would be necessary to establish a statistically significance difference (power 0.8; α 0.05) between the two groups at the 60 min time point.

Calculation of the sample size needed to demonstrate non-inferiority, and stating conclusions that are consistent with aims and results are critical issues when designing or evaluating non-inferiority trial. ³³ In the present experiment, due to the low number of animals enrolled, there is not enough statistical power to conclude that PO tramadol, when compared with IM tramadol, provides non-inferior analgesia at the 60 min time point. However, GOT had a statistically significantly lower highest postoperative pain score than GIMT. Furthermore, the need for rescue analgesia may also be used to evaluate the efficacy of analgesic drugs and none of the cats from GOT required rescue analgesia.^16,34

Conclusions

Within the conditions of the present study, tramadol administered PO as a premedication at 6 mg/kg provided effective postoperative analgesia for at least 6 h to treat acute pain resulting from ovariohysterectomy in cats. Further study should be conducted to confirm if tramadol PO can be considered as an alternative treatment in cats experiencing moderate pain that cannot receive IV or IM medications.