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Comparison of the effects of dipyrone, meloxicam and of the dipyrone/meloxicam combination on postoperative pain and on hemostasis in bitches submitted to ovariohysterectomy

Abstract

This study aims to compare the postoperative analgesic effects produced by a single dose of dipyrone, meloxicam, and by a dipyrone/meloxicam combination in dogs that underwent ovariohysterectomy. The formulated hypothesis is that the postoperative analgesic effects of dipyrone would be similar to those produced by meloxicam, while the meloxicam/dipyrone combination would result in better analgesia than the analgesia observed when each drug is given alone. This study also aims to compare the hemostatic effects (buccal mucosal bleeding time, platelet aggregometry, and thromboelastography) of dipyrone, meloxicam, and of the dipyrone/meloxicam combination during the perioperative period. It was hypothesized that, similarly to what has been reported in humans (Geisslinger et al., 1996; Bozzo et al., 2001; Graff et al., 2007), dipyrone would inhibit the primary hemostasis via inhibition of platelet aggregation. On the other hand, it was hypothesized that meloxicam would not alter platelet aggregation/primary hemostasis (Jones et al., 2002; Fresno et al., 2005; Brainard et al., 2007).Forty bitches scheduled to ovariohysterectomy surgery will be randomly assigned to 4 groups (n = 10 per group): control (CG), dipyrone (DG), meloxicam (MG), and dipyrone/meloxicam (DMG)] in a placebo-controlled, double-blinded study design. All animals will premedicated with meperidine (4 mg/kg, IM). After induction of anesthesia with propofol (5-7 mg/kg, IV), an inhalational agent (isoflurane) will be used to maintain surgical depth of anesthesia throughout surgery. Immediately after orotracheal intubation, 30 min prior to commencing surgery, placebo (0.9% NaCl solution), dipyrone (35 mg/kg IV), meloxicam (0.2 mg/kg IV), and the dipyrone (35 mg/kg IV) / meloxicam (0.2 mg/kg IV) combination will be administered to the groups CG, DG, MG, e DMG, respectively. Postoperative pain will be assessed by the Glasgow and Melbourne multidimensional pain scales and by measuring the mechanical nociceptive thresholds with an electronic von-Frey analgesiometer. The tip of the analgesiometer will be applied to the skin at a 1 cm distance from middle point of the surgical incision. Pain assessments will be performed ate 2, 3, 4, 6, 8, 12, e 24 hours after test drug injection. In case of unacceptable pain (Glasgow or Melbourne pain scores > 35% of the maximum value), analgesic rescue will be administered by morphine injection (0.3 mg/kg, IM). The buccal mucosal bleeding time, percent of inhibition platelet aggregation, and the thromboelastography will be performed immediately before (baseline), 1, 4, and 12 hours after drug injection. After checking the normality of data distribution, comparisons among groups will be performed by a Kruskall Wallis test followed by a Dunnet's test (skewed data), or by a two-way ANOVA followed by a Tukey's test (normal distribution data). The incidence (number) of analgesic rescues among groups will be compared by the Fisher's exact test (P < 0,05). (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZANUZZO, FELIPE S.; TEIXEIRA-NETO, FRANCISCO J.; THOMAZINI, CAMILA M.; TAKAHIRA, REGINA K.; CONNER, BOBBI; DINIZ, MIRIELY S. Effects of dipyrone, meloxicam, or the combination on hemostasis in conscious dogs. JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, v. 25, n. 4, p. 512-520, JUL-AUG 2015. Web of Science Citations: 4.

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