The effects of intravenous (IV) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MAC_ISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MAC_ISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg⁻¹, 100 µg kg⁻¹ minute⁻¹; dexmedetomidine 2 µg kg⁻¹, 2 µg kg⁻¹ hour⁻¹; or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MAC_ISO by 27.3% (range: 12.5–39.2%), 43.4% (33.3–53.3%) and 60.9% (46.1–78.1%), respectively, when compared to MAC_ISO/_BASAL. The combination resulted in a greater MAC_ISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs.

It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC. Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MAC_ISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg). The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MAC_ISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively. The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MAC_ISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane.

The minimum alveolar concentration MAC of isoflurane was measured in rats chronically treated with WIN 55,212-2. Methods: The MAC of isoflurane was determined in 24 male rats from expiratory samples at time of tail clamping under the following conditions: without treatment MAC(_ISO), in rats treated for 21 days with WIN 55,212-2 MAC(_{ISO + WIN55}), and in rats 8 days after stopping treatment with WIN 55,212-2 (MAC_{ISO + WIN55 + 8D}). Results: The MAC(_ISO) was 1.32 ± 0.06. In the MAC(_{ISO + WIN55}) group, the MAC increased to 1.69 ± 0.09 (28%, p-value ≤ (0.0001). Eight days after stopping treatment with WIN55, the MAC did not decrease significantly, 1.67 ± 0.07 (26%, p-value ≤ 0.0001). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. This effect does not disappear 8 days after discontinuation of treatment with the synthetic cannabinoid.

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

The impacts of morphine and dexmedetomidine on the MAC of isoflurane were studied in rats constantly medicated with the cannabinoid WIN 55,212-2. Methods: Prior to the administration of morphine, the MAC was measured in both untreated rats (MAC _(ISO)) and those treated with a cannabinoid (MAC _{(ISO + CANN)}). The effects of morphine (MAC _{(ISO + MOR)}) and dexmedetomidine (MAC _{(ISO + DEX)}) on untreated rats and rats treated for 21 days with the cannabinoids (MAC _{(ISO + CANN + MOR)}) and (MAC _{(ISO + CANN + DEX}) were also studied. Results: MAC _(ISO) was 1.32 ± 0.06, and MAC _{(ISO + CANN)} was 1.69 ± 0.09. MAC _{(ISO + MOR)} was 0.97 ± 0.02 (26% less than MAC _(ISO)). MAC _{(ISO + CANN + MOR)} was 1.55 ± 0.08 (8% less than MAC _{(ISO + CANN)}), MAC _{(ISO + DEX)} was 0.68 ± 0.10 (48% less than MAC _(ISO)), and MAC _{(ISO + CANN + DEX)} was 0.67 ± 0.08 (60% less than MAC _{(ISO + CANN)}). Conclusions: Medication with a cannabinoid for 21 days augmented the MAC of isoflurane. The sparing effect of morphine on isoflurane is lower in rats constantly medicated with a cannabinoid. The sparing effect of dexmedetomidine on the minimum alveolar concentration of isoflurane is greater in rats repeatedly medicated with a cannabinoid.