Anesthesia and analgesia
-
Anesthesia and analgesia · Sep 1997
Context-sensitive half-times and other decrement times of inhaled anesthetics.
The length of anesthetic administration influences the rate at which concentrations of anesthetics decrease after their discontinuation. This is true for both intravenous (I.V.) and inhaled anesthetics. This has been explored in detail for I.V. anesthetics using computer simulation to calculate context-sensitive half-times (the time needed for a 50% decrease in anesthetic concentration) and other decrement times (such as the times needed for 80% or 90% decreases in anesthetic concentration). However, decrement times have not been reported for inhaled anesthetics. In this report, published pharmacokinetic parameters and computer simulation were used to compare the context-sensitive half-times and the 80% and 90% decrement times of the expected central nervous system concentrations for enflurane, isoflurane, sevoflurane, and desflurane. The context-sensitive half-times for all four anesthetics are small (<5 min) and do not increase significantly with increasing duration of anesthesia. The 80% decrement times of both sevoflurane and desflurane are also small (<8 min) and do not increase significantly with duration of anesthesia. However, the 80% decrement times of isoflurane and enflurane increase significantly after approximately 60 min of anesthesia, reaching plateaus of approximately 30 and 35 min. The 90% decrement time of desflurane increased slightly from 5 min after 30 min of anesthesia to 14 min after 6 h of anesthesia. It remained significantly less than the 90% decrement times of sevoflurane, isoflurane, and enflurane, which reached values of 65 min, 86 min, and 100 min, respectively, after 6 h of anesthesia. ⋯ The major differences in the rates at which desflurane, sevoflurane, isoflurane, and enflurane are eliminated occur in the final 20% of the elimination process.
-
Anesthesia and analgesia · Sep 1997
Randomized Controlled Trial Clinical TrialThe influence of three L-type calcium channel blockers on morphine effects in healthy volunteers.
Numerous animal studies and several clinical studies have shown that calcium channel blockers (CCBs) augment opioid analgesia. We sought to determine whether three CCBs from three L-type subgroups (i.e., L-CCBs) enhanced morphine analgesic effects in healthy volunteers, and whether other effects of morphine (e.g., mood-altering effects) were altered by the CCB pretreatment. We examined the effects of three L-CCBs--diltiazem (30 mg, per os [P.O.]), nimodipine (60 mg, P.O.), and verapamil (80 mg, P.O.)--on morphine (10 mg/70 kg, intravenously) effects in nine healthy volunteers. Subjects first ingested the oral drug or placebo and 120 min later were injected with morphine or saline. Dependent measures included pain ratings measured during a cold-pressor test and subjective, psychomotor, and physiological effects. The L-CCBs alone had no effect on any of the dependent measures. Morphine alone and in combination with the L-CCBs reduced pain ratings, but there were no statistically significant differences in the pain measures between the morphine alone and the L-CCB/morphine conditions. Pretreatment with the L-CCBs in most cases neither potentiated nor attenuated the other effects of morphine. L-CCBs as well as the N-type CCBs currently under drug development should continue to be investigated to determine their potential as analgesic adjuvants. ⋯ This study is important because the results are at odds with numerous animal studies and several clinical studies, which indicate that calcium channel blockers of the L-type increase the amount of analgesia produced by morphine. Using clinically relevant doses of L-type blockers, we could find no potentiation of morphine analgesia.