Open Veterinary Journal, (2026), Vol. 16(4): 2082-2094

Research Article

10.5455/OVJ.2026.v16.i4.13

Perioperative analgesia and clinical safety of dexketoprofen in dogs undergoing ovariohysterectomy

Ismael Hernández-Avalos^1*, Navid Ziaei-Darounkolaei², Nadia Crosignani-Outeda³, Pedro Sánchez-Aparicio⁴, Alejandra García-Peralta¹, Alejandro Casas-Alvarado⁵, María del Rosario Arvizu-Venegas⁶ and Agatha Elisa Miranda-Cortés⁷

¹Clinical Pharmacology and Veterinary Anesthesia, Biological Sciences Department, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México (UNAM), Cuautitlán, México

²Department of Surgery and Radiology, Faculty of Veterinary Medicine, Bab.C., Islamic Azad University,

Babol, Iran

³Department of Clinics and Veterinary Hospital, School of Veterinary, University of the Republic, Montevideo, Uruguay

⁴Department of Veterinary Pharmacology, Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma del Estado de México, Toluca, México

⁵Neurophysiology of Pain, Behavior and Animal Welfare Assessment, DPAA, Universidad Autónoma Metropolitana (UAM), Mexico City, México

⁶Department of Surgery, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México (UNAM), Cuautitlán, México

⁷Pharmacology and Toxicology of Substances of Veterinary Interest, Biological Sciences Department, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México (UNAM), Cuautitlán, México

*Corresponding Author: Ismael Hernández-Avalos. Clinical Pharmacology and Veterinary Anesthesia, Biological Sciences Department, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México (UNAM), Cuautitlán, México. Email: ismael.hernandez [at] cuautitlan.unam.mx

Submitted: 01/12/2025 Revised: 10/03/2026 Accepted: 20/03/2026 Published: 30/04/2026

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ABSTRACT

Background: Perioperative nociception and pain are among the most frequent signs observed following animal surgical procedures. Proper management of perioperative pain is essential for the well-being of animals and the stability of physiological, hemodynamic, biochemical, and behavioral parameters.

Aim: This study aimed to evaluate the analgesic efficacy and clinical safety of dexketoprofen in dogs undergoing ovariohysterectomy (OVH) by assessing liver and kidney function-related serum and blood parameters.

Methods: 30 healthy dogs of different breeds were randomly divided into two groups. G1 (n=15) received dexketoprofen at 1 mg kg⁻¹ PO before surgery, and every 24 hours for 48 hours; and G2 (n=15) was premedicated with meloxicam at 0.2 mg kg⁻¹ IV, which was reduced to 0.1 mg kg⁻¹ every 24 hours for 48 hours. HR, respiratory rate, non-invasive blood pressure, esophageal temperature, pulse oximetry (SpO₂), and end-tidal CO₂were evaluated at the beginning of anesthesia (E_BASAL), placement of Backhaus clamp (E_PINZ), skin incision and abdominal cavity approach (E_INC), ligation and resection of the right ovarian pedicle (E_OvD) and left ovarian pedicle (E_OvI), ligation and resection of the uterus (E_UT), muscle fascia closure (E_MUSC), and skin suturing (E_SUT). Postoperative analgesia was assessed using the Dynamic Interactive Visual Analog Scale, University of Melbourne Pain Scale, and Glasgow Composite Measurement Pain Scale–Short Form at 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Blood and biochemical variables were assessed during E_BASAL and at 48 hours.

Results: G1 showed hemodynamic reactivity in systolic blood pressure to surgical manipulation of E_OvD and E_OvI (p=0.034), as well as in mean arterial pressure and diastolic blood pressure during E_OvI (p=0.012 and p=0.024, respectively), compared to E_BASAL. The esophageal temperature decreased progressively in G1 (p=0.006) and G2 (p=0.003). Postoperative pain scores decreased significantly over time in both groups, with no significant differences between them (p=0.999). Blood count and chemistry values in both groups showed no changes indicative of hematological, hepatic, or renal toxicity.

Conclusion: Dexketoprofen offers effective pain relief with short-term (48 hours) clinical safety similar to that of meloxicam in dogs undergoing OVH, highlighting its potential as a dependable option for multimodal pain management during elective surgical procedures.

Keywords: Analgesia, Dexketoprofen, Dogs, Hepatic toxicity, Renal toxicity.

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Introduction

Perioperative nociception and pain are among the most frequently observed signs following surgical procedures in animals (Mwangi et al., 2018; Jones et al., 2024). Proper treatment and management of perioperative pain are essential for maintaining the well-being and stability of physiological, hemodynamic, biochemical, and behavioral indicators (Hernández-Avalos et al., 2020; Coria-Avila et al., 2022; Dogan et al., 2022). Therefore, these indicators must be carefully monitored and controlled. Failure to address the underlying cause of pain may lead to increased hemodynamic reactivity, heightened surgical stress responses, and elevated postoperative pain scores due to reduced analgesic interventions (Hernández-Avalos et al., 2020). This can, in turn, increase the need for anesthetics and analgesics during the perioperative period (Bradbrook and Clark, 2018; Raja et al., 2020). New surgical techniques, such as instrument shank-assisted ovariohysterectomy (OVH), have been introduced to reduce postoperative pain and surgical stress (Ziaei Darounkolaei et al., 2023). However, analgesic-based pharmacological interventions remain essential for effective pain management and hemodynamic stability maintenance during the perioperative period. Therefore, comprehensive pain management should be recognized as a critical element for achieving favorable outcomes in medical and surgical interventions. This underscores the importance of understanding current clinical practices and veterinarians’ pain management attitudes. For instance, Hugonnard et al. (2004)revealed that although 99.5% of veterinarians expressed interest in treating moderate to severe pain, only 8.1% reported administering opioid analgesics. In contrast, 100% of the respondents used nonsteroidal antiinflammatory drugs (NSAIDs), with meloxicam, carprofen, ketoprofen, and tolfenamic acid being the most commonly used. These findings are further supported by data indicating that 73.1% of veterinarians reported insufficient knowledge regarding opioid use. Moreover, only 17.2% of patients used analgesics during elective procedures, whereas 83.7% used them in more invasive orthopedic surgery (Hugonnard et al., 2004).

Similar attitudes toward the use of perioperative analgesics are observed in Latin America, specifically among Brazilian veterinarians. In this sense, Lorena et al. (2014)reported that the most used opioids were tramadol (79%) and morphine (51%), while the NSAIDs of choice were meloxicam (81%) and ketoprofen (70%). Brazilian veterinarians consider practical experience (64%), national (47%), and regional (43%) meetings to be the primary sources of information for identifying and treating pain in companion animals. Furthermore, the authors reported that Brazilian women and younger graduates rated pain with higher scores, although the frequency and duration of analgesic treatment did not differ between the genders of the raters (Lorena et al., 2014).

Another cross-sectional study on anesthesia and analgesia plans used during OVH in dogs reported that veterinarians commonly employed one of three analgesic approaches: NSAIDs alone (61.7%), a combination of NSAIDs and opioids (29.4%), or NSAIDs in conjunction with a local analgesic (2.8%). The most commonly used NSAIDs were consistent with the previous study, primarily carprofen and meloxicam, while buprenorphine was the most frequently administered opioid (Gates et al., 2020). The practices and attitudes of veterinarians toward providing analgesia are not limited to dogs. A study conducted on cats demonstrated that opioids are primarily administered intraoperatively, whereas NSAIDs are more commonly prescribed for postoperative pain management (Rae et al., 2022).

As evidenced by these findings, the use of NSAIDs remains the most popular approach to pain management in companion animals, with tolfenamic acid, carprofen, and meloxicam being the most commonly utilized medications (Bradbrook and Clark, 2018; Mwangi et al., 2018). This reaffirms that the approach to pain management is similar in all countries, reflecting a positive attitude toward animal pain relief. However, despite their effectiveness, the use of NSAIDs is not without risk, as some case analyses have reported an incidence of NSAID-related toxicity in approximately 3% of dogs (Jones et al., 1992; Khan and McLean, 2012; McLean and Khan, 2018), primarily due to adverse effects on the gastrointestinal (emesis, ulcers, bleeding), hepatic alanine aminotransferase and aspartate aminotransferase (ALT and AST increase), and renal systems (decreased glomerular filtration rate) (Nakagawa et al., 2005; Zanuzzo et al., 2015).

An alternative that has been proposed is the use of dexketoprofen, the active S-enantiomer of racemic ketoprofen, which has demonstrated analgesic efficacy comparable to that of meloxicam, carprofen, and tolfenamic acid, while potentially offering a more favorable safety profile. These advantages include its rapid action and strong analgesic potency for managing acute pain, as well as improved digestive tolerability often seen with short-term use (Moore and Barden, 2008; Gelir, 2016). Nevertheless, data regarding the analgesic and overall clinical efficacy of dexketoprofen in dogs are limited. Therefore, this study aimed to evaluate the analgesic efficacy and clinical safety of dexketoprofen in dogs undergoing OVH by assessing liver and kidney function-related serum and blood parameters. Hypothesis 1 mg kg⁻¹ dexketoprofen could provide clinical safety comparable to meloxicam while effectively managing nociceptive and painful responses in dogs undergoing OVH.

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Materials and Methods

Animals

This clinical trial was a prospective, randomized, and blinded trial. Before conducting the study, informed consent was obtained from the animal owners who authorized the procedures. This study included 30 female dogs. The dogs had an average age of 2.8 ± 1.6 years and an average body weight of 11.23 ± 5.56 kg. The sample size was calculated using G*Power 3.1.9.7 software (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany), with a power (error probability 1-β) of 0.90, an error probability α of 0.05, and a confidence level of 95%.

All animals in the study underwent a pre-anesthetic assessment that included a thorough physical examination, chest radiographs, and laboratory tests—complete blood count, serum biochemistry, and urinalysis—performed 48 hours prior to surgery. We included clinically healthy animals, as well as those with only mild conditions that did not impact the thoracic or abdominal cavity, provided they met ASA I-II anesthetic risk criteria (Doyle et al., 2020). Patients with ASA III or higher were excluded. Animals showing signs of anemia, dehydration, uremia, diabetes mellitus, obesity, or hypertension were also excluded.

Experimental design

All animals (n = 30) were randomly assigned into two groups according to the treatment: G₁ (n=15) received dexketoprofen (Stadium, Sanfer, Mexico) at 1 mg kg⁻¹ orally (PO) before and after surgery every 24 hours for 48 hours (Gutiérrez-Bautista et al., 2018); and G₂ (n = 15) received 0.2 mg kg⁻¹ intravenous (IV) meloxicam (Meloxijet, Norvet, Mexico); the dose was reduced to 0.1 mg kg⁻¹ every 24 hours postoperatively for 48 hours. Both drugs were administered 45 minutes before surgery.

The cardiorespiratory parameters were evaluated at the beginning of general anesthesia (E_BASAL), Backhaus clamp placement (E_PINZ), skin incision and approach to the abdominal cavity (E_INC), ligation and resection of the right ovarian pedicle (E_OvD), ligation and resection of the left ovarian pedicle (E_OvI), ligation and resection of the uterus (E_UT), muscle fascia closure (E_MUSC), and skin suture (E_SUT) events. Postoperative analgesia was assessed using the Dynamic Interactive Visual Analog Scale (DIVAS), University of Melbourne Pain Scale (UMPS), and Glasgow Composite Measurement Pain Scale–Short Form (GCMPS-SF) at 1, 2, 4, 6, 8, 12, 24, and 48 hours Blood and Biochemical variables were also assessed 48 hours before and 48 hours after the anesthetic-surgical procedure and at 48 hours after surgery.

Anesthesia and perioperative management

The surgical site was prepared by performing a ring-shaped trichotomy on the forearm, extending from the elbow to the wrist base. After aseptic cleaning, a sterile 20G × 31 mm or 22G × 25 mm IV catheter was inserted into the cephalic vein, depending on the animal’s weight, to ensure proper fluid therapy infusion (Fulton and Hauptman, 1991). Hartmann’s solution (HT Solution, PiSA, Mexico) was then administered at a rate of 5 ml kg⁻¹ h⁻¹ throughout the anesthetic and surgical procedure (BeneFusion VP1 Vet, Mindray, Germany).

The animals were sedated with dexmedetomidine hydrochloride (Dexdomitor, Zoetis, Mexico) at 2 mcg kg⁻¹ IV. After 10 minutes, the sedation level was assessed using the scale proposed by Grint (Grint et al., 2009). After 5 minutes, anesthetic induction was performed with propofol (Recofol 1%, PiSA, Mexico) at a dose of 2–3 mg kg⁻¹ IV (Branson, 2007). Once a sufficient level of unconsciousness was confirmed—marked by ventromedial eyeball deviation, reduced jaw muscle tone, and no palpebral reflex—an orotracheal intubation was carried out. The tube was then connected to an anesthetic rebreathing circuit with an oxygen flow of 45 ml kg⁻¹ minute⁻¹. Anesthesia was maintained with isoflurane (Sofloran, PiSA, Mexico) vaporized in 100% oxygen. The isoflurane vaporizer dial was initially set at 1.8% and adjusted as necessary to maintain suitable anesthetic depth, aiming for a mean arterial pressure (MAP) between 60 and 90 mmHg, as measured by non-invasive blood pressure (NIBP) in the right forearm. Along with these signs, the ET_ISO was also monitored (ePM12VETc/AA, Mindray, Germany), maintaining a concentration of 1.4% throughout the surgery. Mechanical ventilation was initiated in patients using pressure-controlled mode. Ventilation settings included a mean airway pressure of 10–15 cmH₂O, a positive end-expiratory pressure of 2–3 cmH₂O, and an inspiration-expiration ratio of 1:2. The respiratory rate (RR) was adjusted between 12 and 20 bpm to keep end-tidal CO₂ (ETCO₂) levels between 35 and 45 mmHg (ePM12VETc/AA, Mindray, Germany).

All operations were performed by the same surgeon using a midline approach and a triple hemostatic technique. The same anesthesiologist managed all anesthesia procedures. The evaluator and anesthesiologist were blinded to the treatment assignments. Administration of the inhalant anesthetic was stopped 5 minutes before closing the surgical wound. Extubation occurred after the patient regained the cough reflex, breathed spontaneously, and had the ocular globe centered.

Anesthesia monitoring

Cardiorespiratory parameters were continuously monitored throughout the anesthetic-surgical procedure; however, the physiological variables of interest were recorded only during the intraoperative nociceptive events described in the experimental design. These included heart rate (HR, ECG lead II), NIBP (systolic blood pressure, SBP; diastolic blood pressure, DBP; and MAP) by oscillometry (cuff size was determined when the sleeve covered 40% of the forearm circumference), esophageal temperature (ºC), pulse oximetry (oxygen saturation, SpO₂), RR, and ETCO₂ (ePM12VETc/AA, Mindray, Hamburg, Germany). Monitoring was performed at E_BASAL, E_PINZ, E_INC, E_OvD, E_OvI, E_UT, E_MUSC, and E_SUT time points.

Rescue analgesia and nociceptive

Intraoperative analgesic-nociceptive rescue was given to animals in the study when a 20% increase in MAP and HR compared to baseline parameters was observed (KuKanich and Wiese, 2017). In these cases, lidocaine was administered at 2-mg kg⁻¹ IV (Pisacaina, PiSA, Mexico). The postoperative rescue analgesic, buprenorphine at 0.03 mg kg⁻¹ IV (KuKanich and Wiese, 2017), was administered when pain scores reached ≥50 mm on the DIVAS, ≥10 points on the UMPS, and ≥6 points on the GCMPS-SF (Holton et al., 2001; Hernandez-Avalos et al., 2019).

Laboratory data

To evaluate clinical safety, 6.5 ml of jugular venous blood was drawn; 0.5 ml was placed in a lilac color-coded collection tube with Ethylenediaminetetraacetic acid (BD microtainer, Mexico) for complete blood counts, and 6 ml was placed in a red-stoppered collection tube with a clot activator (BD Vacutainer, Mexico) for serum biochemical tests. The samples were sent to a veterinary clinical analysis laboratory, properly labeled and refrigerated (4℃–8ºC). The parameters evaluated included erythrocytes, hemoglobin, hematocrit, platelets, (ALT/TGP), (AST/TGO), alkaline phosphatase (ALP), direct bilirubin, indirect bilirubin, total bilirubin, creatinine, urea, total protein, albumin, globulins, and glucose. Sampling was performed 48 hours before the anesthetic-surgical procedure and again at 48 hours post-surgery.

Statistical analysis

PRISM version 10.5.0 (California, USA) was used for the statistical analysis. Data normality was assessed using the Shapiro-Wilk test. Parametric data are reported as mean ± standard deviation (SD), whereas non-parametric data are reported as median ± standard error of the mean. To evaluate the antinociceptive and analgesic effect of NSAIDs used as perioperative treatment (dexketoprofen and meloxicam) on physiological and cardiorespiratory indicators (HR, RR, Tº, SpO₂, ETCO₂, SBP, DBP, and MAP), the linear mixed statistical model with a Tukey post-hoc test was used.

The nonparametric Friedman test was used to analyze the DIVAS, UMPS, and GCMPS-SF scales, followed by Dunn’s post hoc test. Serum biochemical parameters (ALT, AST, ALP, direct bilirubin, indirect bilirubin, total bilirubin, urea, creatinine, total protein, albumin, and glucose) and hematological variables (erythrocytes, hematocrit, hemoglobin, and platelets) were analyzed using Student’s t-test. Statistical significance was set at p < 0.05 in all comparisons.

Ethical approval

This study was approved by the Internal Committee for the Care and Use of Experimental Animals (CICUAE; by its acronym in Spanish) of the Faculty of Higher Studies Cuautitlan of the National Autonomous University of Mexico (UNAM) under code C23_22. All work was carried out following the ARRIVE guidelines to enhance the design, analysis, and publication of animal research, as well as in accordance with the Mexican Official Standard NOM-062-ZOO-1999, which covers the technical specifications for the production, care, and ethical use of animals.

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Results

The treatment administration was associated with stable intraoperative cardiorespiratory parameters, effective postoperative pain management, and no evidence of hematological, hepatic, or renal toxicity. All measured cardiorespiratory variables remained within physiological limits, with only minor fluctuations observed in specific events, such as ovarian pedicle manipulation (OPM). Postoperative pain assessments showed a significant reduction in pain over time in both groups across all scoring systems, without intergroup differences. Furthermore, laboratory analyses revealed no significant changes suggestive of systemic adverse effects, indicating the clinical safety of the evaluated protocols.

There were no significant differences between G₁ and G₂ in anesthesia times (p=0.36), surgery times (p=0.25), or anesthetic recovery times (p=0.42), as shown in Table 1.

Table 1. Time points evaluated during the anesthetic-surgical process (Mean ± SD, range in parentheses) of 30 female dogs undergoing elective OVH treated with dexketoprofen (G1, n=15) and meloxicam (G2, n=15).

Cardiorespiratory parameters during the intraoperative period

The cardiorespiratory parameters were found to be within normal physiological limits throughout the intraoperative period (Table 2). No significant differences were observed between treatment groups (p=0.99) or study phases (p=0.99) for HR and SpO₂. Similarly, RR was unaffected by the ventilation settings; however, in group G₂, a statistically significant increase was noted during the E_MUSC and E_SUT phases compared to E_BASAL (p=0.016). A gradual decrease in esophageal temperature was recorded throughout the procedure in both groups (G₁: p=0.006; G₂: p=0.003).

Table 2. Cardiorespiratory parameters (Mean ± SD) of 30 female dogs undergoing elective OVH, treated with dexketoprofen (G₁, n=15) and meloxicam (G₂, n=15).

Regarding NIBP, SBP in group G₁ increased significantly by 31% and 33% during E_OvD and E_OvI, respectively, compared with E_BASAL (p=0.034). A similar pattern was noted in E_OvI for MAP and DBP, with increases of 42% (p=0.012) and 49% (p=0.024), respectively. Two animals from G₁ and one from G₂ received nociceptive rescue during OPM.

Assessment of acute pain

A significant reduction in acute postoperative pain scores was observed in both groups (Table 3). DIVAS values decreased from 12 hours postoperatively (p=0.001), whereas UMPS scores declined at 24 hours in G₁ and 8 hours in G₂ (p=0.0001). Similarly, GCMPS-SF scores showed a significant reduction in 48 hours in both groups compared to baseline (p=0.002). However, no statistically significant differences were found between the treatment groups (p=0.999). In this study, no animal required postoperative rescue analgesia.

Table 3. Pain scale scores (Mean ± SD, range in parentheses) of 30 female dogs undergoing elective OVH treated with dexketoprofen (G₁, n=15) and meloxicam (G₂, n=15).

Laboratory data

Clinical safety assessment revealed no significant changes in hematological and serum biochemical parameters in either group postoperatively (p > 0.05), indicating the absence of hematological, hepatic, or renal toxicity (Table 4). All values remained within the physiological limits.

Table 4. Hematological values (Mean ± SD) 48 hours pre- and 48 hours postoperatively in 30 female dogs undergoing elective OVH treated with dexketoprofen (G₁, n=15) and meloxicam (G₂, n=15).

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Discussion

This study hypothesized that dexketoprofen could offer safety comparable to meloxicam while effectively controlling nociceptive and pain responses in female dogs undergoing OVH. The results from nociceptive assessments and pain scoring suggest that dexketoprofen has similar effectiveness to meloxicam in managing postoperative pain, without causing undesirable side effects such as cardiovascular depression, which are usually associated with opioid drugs in female dogs subjected to OVH. 

Cardiorespiratory and physiologic parameters

During pedicle dissection, SBP, MAP, and DBP showed a significant increase in G₁ (p=0.034, p=0.012, and p=0.024, respectively). These hemodynamic changes are likely caused by increased nociceptive stimulation resulting from surgical trauma, which activates the sympathetic nervous system and raises blood pressure. Previous studies, such as Mansour et al. (2017) and Hernández-Avalos et al. (2021), have demonstrated that a 20% increase in HR and MAP from baseline values may indicate nociceptive stimulation. In addition, structures related to the ovarian pedicle, which are significantly affected by sympathetic nerves, may be especially sensitive to nociceptive stimuli. These effects could trigger a generalized hemodynamic response regulated by the brain, particularly by the rostral ventrolateral medullary area (RVLM) (Bond et al., 1980; Cervero, 1994). When activated by pain stimuli, these catecholaminergic neurons cause vasoconstriction and higher blood pressure (Hernández-Avalos et al., 2021a,b; Casas-Alvarado et al., 2023). This response, which is linked to a broad vasomotor response, can be moderated at the ventrolateral medullary level. Neurons in RVLM play a key role in regulating the baroreflex, increasing sympathetic activity, and raising blood pressure (Ally, 1998). According to Marina et al. (2011), acute stress responses, including nociceptive stimulation, activate catecholaminergic neurons in RVLM. The hypothalamus is thought to centrally coordinate this autonomic response, with catecholamine release from the adrenal medulla contributing to vasomotor regulation (Cravo et al., 2003).

The use of perioperative NSAIDs enables pharmacological control of the nociceptive response during the neurobiological stages of transduction, transmission, and modulation, thereby decreasing hemodynamic fluctuations during surgery (Gharagozloo et al., 2015; Saritas et al., 2015). Although an increase in hemodynamic response was observed in this study, these changes did not exceed the physiological limits set for dogs. This is important because a lack of analgesics can lead to a greater need for anesthetics to control the hemodynamic effects of increased sympathetic activity (Palomba et al., 2020; Costa et al., 2023). However, this might also lead to longer surgery, anesthesia, and recovery times due to increased anesthetic requirements, a factor not observed in this study.

Sympathetic activation may arise from factors beyond surgical manipulation, such as the administration of α₂-adrenergic agonists, which transiently increase blood pressure (Thorvaldson et al., 1989; Enouri et al., 2008). This effect has been described as lasting up to 30 minutes, during which the bradycardia can decrease cardiac output. Consequently, an increase in blood pressure helps maintain systemic blood perfusion (Bloor et al., 1992; Kellihan et al., 2015).

Dexmedetomidine was administered as an IV bolus of 2 mcg kg⁻¹ to induce sedation, with minimal cardiovascular effects and no significant respiratory impact. An additional benefit is its role in reducing postanesthesia dysphoria or delirium, facilitating a smoother recovery (Di Franco et al., 2023). An experimental study on auditory and somatosensory evoked potentials revealed that sedation is achieved at 1 mcg kg⁻¹ h⁻¹, whereas effective analgesia requires 3 mcg kg⁻¹ h⁻¹ (van Oostrom et al., 2011). This indicates that the clinical signs of sedation do not necessarily coincide with analgesic effects; therefore, administering other analgesics, such as NSAIDs, to better modulate nociceptive effects resulting from surgery will always be important.

The routes of administration, onset of action, and pharmacokinetics of the two analgesic treatments differ—which could have affected intraoperative nociceptive responses, especially during OPM—the study groups remained comparable. This is because the pharmacokinetic parameters of dexketoprofen are similar whether administered intravenously or orally. Specifically, after oral intake, dexketoprofen has an absolute bioavailability of 85%–89%, with a Cmax of 2.02–12.47 mg/ml and a Tmax of 0.43–0.76 hours (around 26–45 minutes), depending on the dose (1–3 mg/kg) (Serrano-Rodríguez et al., 2014).

Additionally, the minor variations in intraoperative ETCO₂ values observed in this study could be attributable to changes in ventilatory parameters during anesthesia (Hopper and Powell, 2013). Neto et al. (2002) reported that the physiological values for this parameter in standard ventilation were 36 ± 5 mm Hg using a sidestream capnograph. Although these ETCO₂ values were similar to those we observed, Grubb et al. (2020) suggested that the minimum acceptable value should be 35 mm Hg in dogs. This may indicate that some subjects in our study experienced hypocapnia, which is a common complication of prolonged anesthesia. In this clinical trial, the animals remained under anesthesia for 51.9 ± 6.7 minutes in G₁ and 52.8 ± 6.4 minutes in G₂. During this period, no decrease in cerebral oxygenation or development of cardiac arrhythmias—potentially related to electrolyte imbalances such as calcium—was observed. Another key point is that hypocapnia is usually linked to hyperventilation, often with a RR of approximately 28 breaths per minute, which was not observed in this study (Neto et al., 2002).

A progressive decrease in body temperature was observed throughout the surgical procedure in both G₁ and G₂ (p < 0.05), primarily attributed to the hypothermic effects of inhalant anesthetics. Verduzco-Mendoza et al. (2021) and Nakamura and Morrison (2010) reported that the GABAergic action of these agents may inhibit sympathetic vasomotor neurons located in the bulbospinal pathway of the rostral ventrolateral medulla, potentially leading to peripheral vasodilation (Lacerda et al., 2003; Wenker et al., 2017). This vasodilation not only contributes to hypotension but also facilitates heat loss to the environment by enhancing peripheral heat transfer mechanisms (Romanovsky, 2014). Additional factors contributing to hypothermia include direct contact with the surgical table and cold IV fluid administration. These factors promote heat loss through conduction and convection, thereby compromising the thermoregulatory capacity of the body (Urits et al., 2019).

Postoperative assessment of the acute pain

In the present study, no animal required rescue analgesia postoperatively. Therefore, no dog experienced continuous acute postsurgical pain beyond the normal healing period, and no animal developed risk factors associated with persistent postsurgical pain. This type of pain is localized to the surgical field or a nerve innervation area located within the surgical field after surgery on deep somatic or visceral tissue, and persists for at least 3–6 months (Fuller et al., 2023; Monteiro et al., 2023). The analgesic capacity of both treatments—dexketoprofen and meloxicam—is reflected in the scores obtained on the DIVAS, UMPS, and GCMPS-SF scales, with a gradual decrease in scores observed in both G₁ and G₂ (p < 0.05). These findings align with those reported by Morgaz et al. (2013), Bautista et al. (2018), and Saritas et al. (2015), who noted that dexketoprofen exhibits analgesic efficacy comparable to that of meloxicam, buprenorphine, or methadone in the postoperative period. Notably, dexketoprofen provides the advantage of avoiding cardiorespiratory depressant effects commonly associated with opioid use. 

The mechanism of action of dexketoprofen involves the non-selective inhibition of COX-1 and COX-2, which can influence not only peripheral nociceptive pathways but also central mechanisms involved in pain processing by modulating primary afferent fiber responses. This pharmacological action helps reduce the risk of both peripheral and central sensitization (Ellison, 2017).

Experimental studies have reported that NSAIDs can inhibit COX-2 expression in the dorsal horn of the spinal cord, thereby preventing the synthesis and release of neuroactive substances such as substance p, serotonin, histamine, and proinflammatory cytokines (Maihöfner et al., 2000; Vanegas et al., 2001; Tegeder et al., 2008). These findings support the conclusion that the administration of dexketoprofen offers an analgesic efficacy similar to that of meloxicam in the surgical context, as observed in this study.

Laboratory data and safety

The results suggest that dexketoprofen is clinically safe; no differences were observed in hematological parameters between different time points or treatment groups. This is consistent with the findings of Llambo-Villacrés et al. (2018), who reported that dexketoprofen administration did not affect markers such as ALT, AST, Gamma-Glutamyl Transferase (GGT), blood urea nitrogen, and Creatinine during the postoperative period in dogs. These observations agree with the current findings and are further supported by Saritas et al. (2015), who found no alterations in total protein, urea, ALT, albumin, and GGT levels.

Most NSAIDs are metabolized by glucuronidation, a process that frequently generates active metabolites responsible for toxic effects at the hepatic, gastrointestinal, and renal levels (Lascelles et al., 2005; Khan and Mclean, 2012; McLean and Khan, 2018). Dexketoprofen undergoes extensive biotransformation into inactive metabolites that are subsequently excreted by the kidneys (Barbanoj et al., 2001). This metabolic profile may explain the absence of hepatotoxic or nephrotoxic effects, supporting the clinical safety of the dose used in this study.

Limitations and perspectives

This study has several limitations, including the lack of comparison with drugs that have higher analgesic potency, such as methadone or other opioids, which could provide stronger validation for this novel treatment’s efficacy. It also suggests exploring alternative surgical models; for example, evaluating the analgesic effect of this molecule in more invasive procedures, such as orthopedic or trauma surgeries, would be relevant. Although recent advances in surgical techniques, such as shank-assisted OVH (a single-person modified approach), aim to reduce surgical stress and postoperative pain, these methods alone may not completely eliminate nociception (Ziaei Darounkolaei et al., 2023). Despite the potential benefits of such surgical modifications, managing postoperative pain remains a crucial aspect. Therefore, the use of NSAIDs continues to play a vital role in pain control and maintaining stable hemodynamic parameters during the perioperative period. In this context, drugs such as dexketoprofen, which have shown an analgesic efficacy comparable to traditional NSAIDs, are essential to ensure optimal outcomes, especially when surgical techniques alone cannot provide complete pain relief. Furthermore, the combination of effective analgesic protocols with refined surgical techniques remains the gold standard for managing perioperative pain in veterinary practice, as evidenced by previous studies.

Another potential limitation is the absence of methods with higher sensitivity and specificity for measuring hemodynamic parameters, such as invasive blood pressure (IBP), which is regarded as the gold standard (Bailey et al., 2025). However, Vachon et al. (2014)highlighted that oscillometry devices are more reliable than Doppler in determining blood pressure in medium- and large-breed dogs (whether conscious or anesthetized) because they meet more criteria outlined by the consensus statement of the American College of Veterinary Internal Medicine. Despite this, their study showed that noninvasive methods slightly underestimated SBP in anesthetized patients. These findings agree with those of Drynan and Raisis (2013), who demonstrated that the agreement between NIBP and IBP measurements falls within the limits recommended by the American College of Veterinary Internal Medicine Hypertension Consensus Panel for all blood pressures except SBP. These results suggest that, at a minimum, MAP and DBP can be considered clinically acceptable alternatives to invasive methods in dogs with hypovolemia when using the Surgivet V9203 monitor. Additionally, this limitation suggests that other more reliable techniques, such as the bispectral index, could be used to assess intraoperative nociception, since its measurement has been linked to autonomic nervous system stability (Lascelles et al., 2005). Other limitations of this study include the absence of intraoperative time point measurements for each specific moment and the lack of pharmacokinetic data, such as Cmax, Tmax, and AUC, which would enable a more detailed correlation of the analgesic effects of dexketoprofen. This last limitation could also serve as a future perspective, as determining each time point and measuring PK parameters would allow the estimation of responses to nociceptive stimuli of both greater intensity and longer duration.

Because laboratory assessments were only conducted within 48 hours after surgery, we could not identify any late hepatic or renal toxicity related to dexketoprofen use. This limitation should be noted in future research. Likewise, future studies could benefit from correlating subjective pain scales with objective markers of nociception, such as the parasympathetic tone index, infrared thermography, pupillometry, surgical pleth index, and bispectral index, which would enhance the robustness of clinical pain assessments.

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Conclusion

Dexketoprofen demonstrated perioperative analgesic efficacy and short-term (48 hours) clinical safety comparable to that of meloxicam in female dogs undergoing OVH, suggesting its potential as a reliable alternative for multimodal pain management in routine surgical procedures.

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Acknowledgments

Secretariat of Science, Humanities, Technology and Innovation (SECIHTI, by its Spanish acronym); CVU 748873, solicitude 406765.

Conflict of interest

The authors declare no conflict of interest.

Funding

This research received no external funding.

Authors’ contributions

Conceptualization, Ismael Hernández-Ávalos and Agatha Elisa Miranda-Cortés; Formal analysis, Ismael Hernández-Avalos and Alejandro Casas-Alvarado; Investigation, Alejandra García-Peralta, Agatha Elisa Miranda-Cortés, Alejandro Casas-Alvarado, and Pedro Sánchez-Aparicio; Methodology, Alejandra García-Peralta, María del Rosario Arvizu-Venegas, Agatha Elisa Miranda-Cortés, and Ismael Hernández-Ávalos; Resources, Ismael Hernández-Ávalos and Agatha Elisa Miranda-Cortés; Writing – original draft, Ismael Hernández-Ávalos, Navid Ziaei-Darounkolaei, and Nadia Crosignani-Outeda; Writing – review & editing, Agatha Elisa Miranda-Cortés, Alejandro Casas-Alvarado, Navid Ziaei-Darounkolaei, Nadia Crosignani-Outeda, and Pedro Sánchez-Aparicio. All authors have contributed to the approval of the final version of the manuscript. All authors have read and approved the published version of the manuscript.

Data availability

All data supporting this study’s findings are available within the manuscript.

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