Cardiorespiratory effects of intravenous Maropitant-Zenalpha versus Methadone-Zenalpha in dogs undergoing ovariectomy and anesthetized with Propofol and sevoflurane. Preliminary results.

Maropitant and methadone have analgesic effect in canine anesthesia (1). Zenalpha is a 1:20 combination of medetomidine and vatinoxan, in which vatinoxan counteracts peripheral vasoconstriction, increased blood pressure and bradycardia produced by medetomidine (2). The study aimed to evaluate the effect of Zenalpha on invasive blood pressure (IBP) from the first moment after its administration and in a clinical setting, in anesthesia induced with propofol, maintained with sevoflurane and with two analgesics in comparison, i.e. maropitant or methadone. The study was approved by the Ethical Committee of the University of Sassari (prot. N. 0101145/2023). Ten female dogs were randomly divided into two groups of 5 dogs each, administered with maropitant intravenously (IV) 1 mg kg-1 (Maro group) and with methadone IV 0.3 mg kg-1 (Metha group). After 5 min, anesthesia was induced with propofol and maintained in spontaneous ventilation with sevoflurane at 1.3% end expiratory percentage (Et- Sevo) delivered in oxygen at inspiration fraction 0.4. Five min after induction, Zenalpha IV 0.125 mg m-2 (referring to medetomidine) was administered. After another 15 min, surgery began with EtSevo raised to 2.0%. Fentanyl IV 5 μg kg -1 was administered as rescue analgesia. Mean arterial pressure (MAP) with noninvasive method (NIBP), HR and respiratory rate (RR) were recorded 20 min before the trial. Subsequently, MAP in IBP, HR, RR, Minute ventilation per kg of body weight (MV/kg) and end-expiratory carbon dioxide partial pressure (PetCO2) were recorded immediately after induction and then at 2, 3, 6, 15 min, at traction of each ovarian pedicle and close to extubation. The data of the two groups, at each time point, were compared by Mann Whitney test, with significance for P<0.05. Mean arterial pressure increased rapidly in both groups at 2 min after Zenalpha administration and then began to decrease from 3 min onwards, maintaining significantly lower values in Metha group than in Maro group; at 20 min it reached hypotension values (55(50-61) mmHg) in Metha group, while it remained at normal values (between 70(68-73) and 90(86-91) mmHg) in Maro group. Similarly, though in reverse, HR decreased just as rapidly at 2 min after Zenalpha administration and then rose again from 3 min onwards, maintaining at each measurement significantly higher values in Maro group than in Metha group (84(77-87) - 105(92-115) vs 70(69-70) - 78(74-82) beats min-1 respectively). In both groups, only a small, non-significant increase in MAP and HR was observed at ovarian pedicle traction compared to previous values. On the respiratory side, only PetCO2 was significantly higher in Metha group compared to Maro group at 3, 6 and 15 min after administration, while no significance was found in the differences between the two groups regarding RR and MV/kg. No rescue analgesia was required in any dog. Cardiovascular effects of Zenalpha are significantly greater when combined with methadone rather than with maropitant. With the protocol used in this study, the decrease in MAP induced by Zenalpha IV briefly borders on hypotension even at doses 8 times lower than those recommended for the IM route.