Opioids as Anesthetics
Whether opioids alone are capable of producing anesthesia was
a subject of debate in the past.[59]
Reports of
patient awareness during high-dose fentanyl anesthesia highlighted the potential
for this problem (also see Chapter
31
).
The anesthetic potential of opioids was tested by MAC measurement.
[60]
Studies in rats demonstrate that opioids reduce
the MAC of volatile anesthetics to a greater degree than in other animals. Interspecies
differences in opioid actions are significant.[61]
Fentanyl can reduce the MAC of isoflurane at least 80% at skin incisions in humans
( Fig. 11-5
).[62]
It was shown that the relationship between plasma fentanyl concentration and MAC
reduction is not linear, and that a sub-MAC ceiling exists to the effect of fentanyl
on isoflurane MAC reduction. The potency ratios for fentanyl, sufentanil, alfentanil,
and remifentanil, based
Figure 11-5
Reduction of isoflurane minimum alveolar concentration
(MAC) by increasing the concentration of fentanyl. (From McEwan Al, Smith
C, Dyar O, et al: Isoflurane minimum alveolar concentration reduction by fentanyl.
Anesthesiology 78:864–869, 1993.)
on MAC reduction studies in humans, is approximately 1:12:1/16:1.2.[63]
Esmolol, a short-acting β1
-receptor antagonist, significantly decreased
the MAC of isoflurane in the presence of alfentanil, although it did not significantly
affect it in the absence of alfentanil.[64]
The
mechanism of the interaction is unknown. It was demonstrated that epidural fentanyl
infusion reduced the awakening concentration of isoflurane more than intravenous
fentanyl infusion, despite the lower plasma concentration, possibly by modulating
the afferent nociceptive inputs in the spinal cord.[65]
The hypnotic effect of midazolam is also significantly potentiated by alfentanil.
[66]
The bispectral index (BIS) has been proposed as a measure of the
effects of anesthetics on the brain. In the presence of fentanyl, alfentanil, remifentanil,
or sufentanil, loss of consciousness occurred at a lower effect site concentration
of propofol and at a higher BIS value compared with propofol alone.[67]
This result suggests that the hypnotic effect of propofol is enhanced by analgesic
concentrations of opioids without changes in BIS value. On the other hand, it was
reported that infusion of remifentanil (effect site target concentration of 0.5,
2.5 and 10 ng/mL), combined with propofol infusion adjusted to BIS ∼60, dose-dependently
decreased BIS, suggesting a sedative or hypnotic effect of remifentanil.[68]
Although unconsciousness in humans can be produced with high doses
of opioids alone, opioid anesthesia can be unpredictable and inconsistent.[69]
Whether analgesia and loss of consciousness are produced by opioids through a common
mechanism has been questioned. A dual mechanism in the action of opioids has been
proposed, and it was demonstrated that the anesthetic action of opioids requires
lipid solubility.[70]
