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Cyclosporine can increase isoflurane MAC
Claus U Niemann1, Caroline Stabernack, Natalie Serkova
1Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143, USA. niemannc@anesthesia.ucsf.edu
Unlabelled:
Previous reports indicate that cyclosporine increases sleeping time from barbiturate administration, and analgesia from fentanyl administration, suggesting a possible contribution of cyclosporine to anesthesia. Accordingly, we determined whether cyclosporine pretreatment decreases isoflurane MAC (the minimum alveolar concentration of anesthetic required to eliminate movement in response to noxious stimulation in 50% of subjects) in rats, and whether cyclosporine changes the hindpaw withdrawal latency (HPWL) test to thermal nociceptive stimulation. We assigned rats to receive vehicle (control; n = 18), 7.5 mg. kg(-1). d(-1) cyclosporine (n = 10), or 15 mg. kg(-1). d(-1) cyclosporine (n = 20). MAC was determined before and immediately after 3 days of treatment. HPWL was determined after 3 days of treatment in controls (vehicle) and cyclosporine (15 mg. kg(-1). d(-1)) treated animals. Cyclosporine 7.5 and 15 mg. kg(-1). d(-1) increased MAC by 10.4% +/- 7.3% and 23.1% +/- 17.1% (mean +/- SD) (P < 0.05), respectively. The changes in isoflurane MAC correlated significantly with cyclosporine blood concentrations. Cyclosporine did not significantly increase HPWL. Contrary to our hypotheses, cyclosporine increases rather than decreases MAC, but does not confer appreciable analgesia.
Implications:
The immunosuppressive drug, cyclosporine, which is frequently used after organ transplantation, increases the amount of a commonly used anesthetic (isoflurane) necessary to avoid movement to painful stimuli in the rat.
Insights
The immunosuppressive drug cyclosporine increases the required dose of the anesthetic isoflurane in rats, contrary to initial hypotheses. This finding suggests cyclosporine may impact general anesthesia requirements.
Area of Science:
- Anesthesiology
- Pharmacology
- Immunology
Background:
- Cyclosporine, an immunosuppressive medication, has shown potential to influence anesthetic effects in prior studies.
- Previous research indicated cyclosporine may potentiate sedative and analgesic effects of certain drugs.
Purpose of the Study:
- To investigate if cyclosporine pretreatment alters the minimum alveolar concentration (MAC) of isoflurane in rats.
- To determine if cyclosporine affects pain response as measured by hindpaw withdrawal latency (HPWL) to thermal stimulation.
Main Methods:
- Rats were administered vehicle, 7.5 mg/kg/day cyclosporine, or 15 mg/kg/day cyclosporine for three days.
- Isoflurane MAC was measured before and after the treatment period.
- HPWL was assessed in control and high-dose cyclosporine groups post-treatment.
Main Results:
- Cyclosporine significantly increased isoflurane MAC by 10.4% (7.5 mg/kg/day) and 23.1% (15 mg/kg/day).
- The increase in MAC correlated with cyclosporine blood concentrations.
- Cyclosporine did not significantly alter hindpaw withdrawal latency, indicating no significant analgesic effect.
Conclusions:
- Contrary to initial hypotheses, cyclosporine pretreatment increases the dose of isoflurane needed to prevent movement to noxious stimuli in rats.
- Cyclosporine does not appear to confer significant analgesia in this model.
- These findings suggest cyclosporine may necessitate adjustments in anesthetic management.