DRUG INTERACTIONS
No clinically significant adverse interactions with commonly used preanesthetic drugs, or drugs used during anesthesia (muscle relaxants, intravenous agents, and local anesthetic agents) were reported in clinical trials. The effect of SUPRANE (desflurane, USP) on the disposition of other drugs has not been determined. Similar to isoflurane, SUPRANE (desflurane, USP) does not predispose to premature ventricular arrhythmias in the presence of exogenously infused epinephrine in swine.
Benzodiazepines and Opioids (MAC Reduction)
Benzodiazepines and opioids decrease the amount of desflurane (MAC) needed to produce anesthesia. This effect is shown in Table 3 for intravenous midazolam (25-50 µg/kg) and intravenous fentanyl (3-6 µg/kg) in patients of two different age groups.
Table 3
SUPRANE (desflurane, USP) MAC with Fentanyl or Midazolam
Mean ± SD (percent reduction)
|
Dose
|
18-30 years
|
31-65 years
|
No fentanyl |
6.4 ± 0.0 |
6.3 ± 0.4 |
3 µg/kg fentanyl |
3.5 ± 1.9 (46%) |
3.1 ± 0.6 (51%) |
6 µg/kg fentanyl |
3.0 ± 1.2 (53%) |
2.3 ± 1.0 (64%) |
No midazolam |
6.9 ± 0.1 |
5.9 ± 0.6 |
25 µg/kg midazolam |
- |
4.9 ± 0.9 (16%) |
50 µg/kg midazolam |
- |
4.9 ± 0.5 (17%) |
Neuromuscular Blocking Agents
Anesthetic concentrations of desflurane at equilibrium (administered for 15 or more minutes before testing) reduced the ED95 of succinylcholine by approximately 30% and that of atracurium and pancuronium by approximately 50% compared to N2O/opioid anesthesia (see Table 4). The effect of desflurane on duration of nondepolarizing neuromuscular blockade has not been studied.
Table 4
Dosage of Muscle Relaxant Causing 95% Depression in Neuromuscular Blockade
|
Desflurane Concentration
|
Mean ED95 (µg/kg)
|
Pancuronium
|
Atracurium
|
Succinylcholine
|
Vecuronium
|
0.65 MAC 60% N2O/O2
|
26 |
133 |
- |
- |
1.25 MAC 60% N2O/O2
|
18 |
119 |
- |
- |
1.25 MAC O2
|
22 |
120 |
360 |
19 |
Dosage reduction of neuromuscular blocking agents during induction of anesthesia may result in delayed onset of conditions suitable for endotracheal intubation or inadequate muscle relaxation, because potentiation of neuromuscular blocking agents requires equilibration of muscle with the delivered partial pressure of SUPRANE (desflurane, USP).
Among nondepolarizing drugs, pancuronium, atracurium, and vecuronium interactions have been studied. In the absence of specific guidelines:
- For endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants or succinylcholine.
- During maintenance of anesthesia, the dose of nondepolarizing muscle relaxants is likely to be reduced compared to that during N2O/opioid anesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation.
Concomitant use with NO
Concomitant administration of N2O reduces the MAC of SUPRANE (desflurane, USP) [see Dosage and Administration (2), Table 1 ].
Beta Blockers
Concomitant use of beta blockers may exaggerate the cardiovascular effects of inhalational anesthetics, including hypotension and negative inotropic effects.
Monoamine Oxidase Inhibitors (MAO)
Concomitant use of MAO inhibitors and inhalational anesthetics may increase the risk of hemodynamic instability during surgery or medical procedures.
|