Mohammed A. Umar

Interaction between maropitant and carprofen on sparing of the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs

Maropitant, a neurokinin-1 receptor antagonist, may provide analgesic effects by blocking pharmacological action of substance P. Carprofen is a non-steroidal anti-inflammatory drug commonly used for pain control in dogs. The purpose of this study was to evaluate the effect of a combination of maropitant and carprofen on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Six healthy adult beagle dogs were anesthetized with sevoflurane four times with a minimum of 7-day washout period. On each occasion, maropitant (1 mg/kg) alone, carprofen (4 mg/kg) alone, a combination of maropitant (1 mg/kg) and carprofen (4 mg/kg), or saline (0.1 ml/kg) was subcutaneously administered at 1 hr prior to the first electrical stimulation for the sevoflurane MAC-BAR determination. The sevoflurane MAC-BAR was significantly reduced by maropitant alone (2.88 ± 0.73%, P=0.010), carprofen alone (2.96 ± 0.38%, P=0.016) and the combination (2.81 ± 0.51%, P=0.0003), compared with saline (3.37 ± 0.56%). There was no significant difference in the percentage of MAC-BAR reductions between maropitant alone, carprofen alone and the combination. The administration of maropitant alone and carprofen alone produced clinically significant sparing effects on the sevoflurane MAC-BAR in dogs. However, the combination of maropitant and carprofen did not produce any additive effect on the sevoflurane MAC-BAR reduction. Anesthetic premedication with a combination of maropitant and carprofen may not provide any further sparing effect on anesthetic requirement in dogs.

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol (KMP-TIVA) in horses undergoing surgery

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol drug combination (KMP-TIVA) were determined in 5 Thoroughbred horses undergoing surgery. The horses were anesthetized with intravenous administration (IV) of ketamine (2.5 mg/kg) and midazolam (0.04 mg/kg) following premedication with medetomidne (5 µg/kg, IV) and artificially ventilated. Surgical anesthesia was maintained by controlling propofol infusion rate (initially 0.20 mg/kg/min following an IV loading dose of 0.5 mg/kg) and constant rate infusions of ketamine (1 mg/kg/hr) and medetomidine (1.25 µg/kg/hr). The horses were anesthetized for 175 ± 14 min (range from 160 to 197 min). Propofol infusion rates ranged from 0.13 to 0.17 mg/kg/min, and plasma concentration (Cpl) of propofol ranged from 11.4 to 13.3 µg/ml during surgery. Cardiovascular measurements during surgery remained within clinically acceptable ranges in the horses (heart rate: 33 to 37 beats/min, mean arterial blood pressure: 111 to 119 mmHg, cardiac index: 48 to 53 ml/kg/min, stroke volume: 650 to 800 ml/beat and systemic vascular resistance: 311 to 398 dynes/sec/cm5). The propofol Cpl declined rapidly after the cessation of propofol infusion and was significantly lower at 10 min (4.5 ± 1.5 µg/ml), extubation (4.0 ± 1.2 µg/ml) and standing (2.4 ± 0.9 µg/ml) compared with the Cpl at the end of propofol administration (11.4 ± 2.7 µg/ml). All the horses recovered uneventfully and stood at 74 ± 28 min after the cessation of anesthesia. KMP-TIVA provided satisfactory quality and control of anesthesia with minimum cardiovascular depression in horses undergoing surgery.

Comparison of pharmacokinetics of tramadol between young and middle-aged dogs

This study aimed to compare the pharmacokinetics of tramadol between young and middle-aged dogs. Tramadol (4 mg/kg) was administered intravenously (IV) to young and middle-aged dogs (2 and 8–10 years, respectively). Plasma concentrations of tramadol were measured using high-performance liquid chromatography (HPLC), and its pharmacokinetics best fit a two-compartment model. The volume of distribution (Vd), elimination half-life (t1/2,β) and total body clearance (CLtot) of the young group were 4.77 ± 1.07 l/kg, 1.91 ± 0.26 hr and 29.9 ± 7.3 ml/min/kg, respectively, while those of the middle-aged group were 4.73 ± 1.43 l/kg, 2.39 ± 0.97 hr and 23.7 ± 5.4 ml/min/kg, respectively. Intergroup differences in the t1/2,β and CLtot were significant (P<0.05). In conclusion, tramadol excretion was significantly prolonged in middle-aged dogs.

Influence of sevoflurane anesthesia with mechanical ventilation and fluid-therapy on distribution of subcutaneously administered robenacoxib in dogs

Robenacoxib is a novel nonsteroidal anti-inflammatory drug approved for dogs. The present study aimed to evaluate influences of sevoflurane anesthesia on the distribution of robenacoxib in dogs. Ten healthy beagle dogs (1 to 11 years old, 9.3 to 14.3 kg body weight, 6 males and 4 females) were subcutaneously administered robenacoxib (2 mg/kg) under conscious condition or sevoflurane anesthesia inhaled a 1.3-fold predetermined individual minimum alveolar concentration of sevoflurane at a 28-day interval. The dogs under sevoflurane anesthesia were also mechanically ventilated and received fluid-therapy. On each occasion, serum samples were collected from the dogs before and at 5, 15, 30, 60, 120, 180, and 240 min after the robenacoxib administration. Serum robenacoxib concentration was measured by a liquid chromatography-tandem mass spectrometry. Maximum serum concentration of robenacoxib (Cmax) was 2.2 µg/ml [range: 1.2–4.6] (median [range: minimum-maximum]) and time of Cmax (Tmax) was 90 min [range: 60–120] in the conscious dogs. In the sevoflurane-anesthetized dogs, the Cmax significantly declined (1.3 µg/ml [range: 0.8–1.4], P=0.008) and Tmax was delayed (120 min [range: 120–240], P=0.018) compared with those in the conscious dogs. The serum robenacoxib concentration at 240 min (C240) decreased to 0.5 µg/ml [range: 0.2–0.9] in the conscious dogs, while it remained higher in the sevoflurane-anesthetized dogs (1.0 µg/ml [range: 0.3–1.4], P=0.011). In conclusion, the anesthetic procedure with sevoflurane, mechanically ventilated, and received fluid-therapy might affect the pharmacokinetics of subcutaneously administered robenacoxib in dogs.