A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery.

OBJECTIVE: To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration. ANIMALS: 72 client-owned mixed-breed cats undergoing ovariohysterectomy or castration between October 4, 2018, and January 10, 2020. PROCEDURES: For each type of surgery, cats were assigned to 1 of 6 premedication protocols groups, with 6 cats/group: physiologic saline (0.9% NaCl) solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IV); physiologic saline solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IM); medetomidine (50 µg/kg, IM) and alfaxalone (5 mg/kg, IV); medetomidine (50 µg/kg, IM) and alfaxalone (5 mg/kg, IM); midazolam (0.5 mg/kg, IM), medetomidine (50 µg/kg, IM), and alfaxalone (5 mg/kg, IV); or midazolam (0.5 mg/kg, IM), medetomidine (50 µg/kg, IM), and alfaxalone (5 mg/kg, IM). Venous blood was taken before pretreatment, pre- and postoperatively during anesthesia with isoflurane and oxygen, and during early and complete recovery. RESULTS: Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine. The combination of medetomidine, midazolam, and alfaxalone prevented an excessive increase in catecholamines during anesthesia and surgery in cats. Postoperative plasma cortisol concentration after ovariohysterectomy was lower for cats premedicated with the combination of medetomidine and alfaxalone or the combination of medetomidine, midazolam, and alfaxalone, compared with cats premedicated with alfaxalone alone. Cats treated with combinations that included medetomidine and midazolam had hyperglycemia during anesthesia. Cats treated with medetomidine or medetomidine and midazolam in combination with alfaxalone, compared with alfaxalone alone, had lower concentrations of nonesterified fatty acids during anesthesia. Behavioral recovery scores were lower (better) for cats that received medetomidine in addition to alfaxalone, compared with alfaxalone alone. CLINICAL RELEVANCE: Results indicated that pretreatments with medetomidine and alfaxalone or with medetomidine, midazolam, and alfaxalone were useful for preventing stress-related hormonal and metabolic responses, other than hyperglycemia, during isoflurane anesthesia and surgery in cats.

Reversal effects of atipamezole, flumazenil, and 4-aminopyridine on bradycardia and increases in blood pressures induced by medetomidine, midazolam, and ketamine in isoflurane-anesthetized cats.

OBJECTIVE: To investigate the effects of a fixed dose of atipamezole (AT), flumazenil (FL), and 4-aminopyridine (AP), both alone and in combination, on changes in arterial blood pressure and heart rate induced by medetomidine (ME), midazolam (MI), and ketamine (KE) under isoflurane anesthesia with controlled ventilation in healthy cats. DESIGN: Prospective experimental study. SETTING: University animal research facility. ANIMALS: Healthy adult mixed-breed cats were used for 8 investigation groups (6 cats per group), with ≥2 weeks between interventions. INTERVENTIONS: Cats were anesthetized with an end-tidal isoflurane concentration of 2% under controlled ventilation. A catheter was inserted into the right or left femoral artery for arterial pressure monitoring and blood gas sampling, and ECG electrodes were placed. Upon completed preparations, cats were administered a mixture of ME (0.05 mg/kg) and MI (0.5 mg/kg), followed 10 minutes later by intramuscular KE (10 mg/kg). Twenty minutes after KE injection, the cats received IV injection with either a physiological saline solution at 0.1 mL/kg (control), or 1 of 7 variations of experimental drugs, alone or in combination: AT (0.2 mg/kg), FL (0.1 mg/kg), AP (0.5 mg/kg), AT+FL, FL+AP, AT+AP, and AT+FL+AP. Arterial blood pressure and heart rate were continuously measured over 120 minutes after administration of potential antagonists. MEASUREMENTS AND MAIN RESULTS: ME+MI+KE induced an increase in blood pressure and bradycardia. Potential antagonists alone or in combination did not significantly alter the bradycardia. FL, AP alone, and FL+AP did not significantly alter the changes in blood pressures induced by ME+MI+KE. Meanwhile, administration of AT alone or in combination reversed the increase in blood pressure induced by ME+MI+KE but transiently caused excessive hypotension. CONCLUSION: These results revealed that AT alone or in combination is effective for antagonizing hypertension induced by ME+MI+KE; however, attention should be paid to temporary hypotension in cats anesthetized with isoflurane.

Effects of pretreatment with medetomidine, midazolam, ketamine, and their combinations on stress-related hormonal and metabolic responses in isoflurane-anesthetized cats undergoing surgery.

OBJECTIVE: The purpose of this study was to compare the effects of pretreatment with medetomidine (Me), midazolam (Mi), and ketamine (Ke) on stress-related neurohormonal and metabolic responses in isoflurane-anesthetized cats undergoing ovariohysterectomy and castration. MATERIALS AND METHODS: We prospectively recruited 112 client-owned healthy mixed-breed cats. In both surgeries, we divided the cats into seven groups (eight cats per group): non-treatment (control), Me (50 µg/kg), Mi (0.5 mg/kg), Ke (5 mg/kg), Me + Mi, Me + Ke and Me + Mi + Ke administered intramuscularly. After pretreatments, we maintained anesthesia with isoflurane and oxygen. Venous blood was taken before pretreatment, pre- and post-operatively during anesthesia, and at early- and complete-recovery. RESULTS: Both plasma adrenaline and noradrenaline were reduced during anesthesia in all groups. Plasma cortisol increased during anesthesia and at early recovery in non-Me-treated groups, whereas it decreased in Me-treated groups in both surgeries. Plasma insulin and non-esterified fatty acid (NEFA) decreased, and glucose increased during anesthesia in all groups, but hyperglycemia and decrease in NEFA were greater in Me-treated groups. CONCLUSIONS: In isoflurane-anesthetized cats undergoing surgeries, premedication with Me alone and in combination is useful for reducing the perioperative stress-related increase in cortisol and catecholamines except for hyperglycemia.