Alfentanil Potentiates Midazolam-Induced Unconsciousness in Subanalgesic Doses

Abstract

The effects of alfentanil on the midazolam dose-response curve for hypnosis was studied with response to the verbal command as an end point in 95 patients. The analgesic effect of alfentanil was studied by measuring the threshold for pain caused by pressure on the trapezius muscle with the use of a dolorimeter in 21 patients. The study was randomized, double-blind, and performed on the unpremedicated patients with ASA physical status I or II. Alfentanil was found to reduce the midazolam ED50 value for the induction of anesthesia in a dose-dependent fashion. The smallest dose of alfentanil (3 micrograms/kg) that caused a marked shift of the midazolam dose-response curve to the left along the dose axis (from the ED50 of 270 micrograms/kg to the ED50 of 142 micrograms/kg, P less than 0.0005) represents approximately 2% of the alfentanil ED50 for induction of unconsciousness (130 micrograms/kg). Alfentanil (10 micrograms/kg) caused only a tendency for increase in the pain threshold, whereas a dose of 15 micrograms/kg significantly increased the pain threshold by 37% (P less than 0.05). The results demonstrate that alfentanil potentiates the hypnotic effect of midazolam in very small doses. The high potency of alfentanil in this respect, as compared to its analgesic potency, suggests a very specific mechanism of alfentanil-midazolam hypnotic interaction, one that most likely is based on a functional relationship between the GABA receptor-benzodiazepine receptor system and the opioid receptor system in mediation of hypnosis.

Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients

“…Shelly et al [13] reported the impaired ability of critically ill patients with septic shock to metabolise midazolam, possibly due to reduced organ perfusion, leading to accumulation of the drug. Pharmacodynamic interactions between different drugs may also conceivably result in potentiation; there are indications that opioids, even in small doses, can enhance the hypnotic effect of benzodiazepines [14]. These interactions might result in oversedation if the potentiation of one drug by another is not taken into account.…”

Remifentanil plus low-dose midazolam for outpatient sedation in transesophageal echocardiography

“…[17,18]. Aiming to minimizing potential drugrelated side effects, we chose to administer patients in the RM group small doses of each drug (particularly midazolam), taking into consideration the well-studied synergism between midazolam and opioids [7,8,9,10]. Although we did not measure pCO2 by means of arterial blood samples, any effect of the remifentanil-midazolam combination on patients' ventilatory drive was clinically of little importance as it was not associated with oxygen desaturation or any other untoward clinical event.…”

“…Due to its rapid elimination and dose-independent kinetics, the effects of remifentanil may be modulated in real time without the need for reversal by opioid antagonists such as naloxone. On the basis of the well known synergistic effects between opioids and midazolam [7][8][9][10], we hypothesized that the favourable characteristics of remifentanil, synergistically combined with a very low-dose of midazolam (0.5 mg IV), would confer a significant advantage over a sedation protocol based on midazolam alone. We report a controlled pilot study with the primary end-point of a modified Aldrete's score as a surrogate of time-to-discharge.…”

A Comparison of Effects of Alfentanil, Fentanyl, and Remifentanil on Hemodynamic and Respiratory Parameters During Stereotactic Brain Biopsy

“…Additionally, these 2 groups of agents interact favorably with regard to the hypnotic component of anesthesia. [2][3][4][5] However, excessive use of these drugs can produce lifethreatening complications. 6,7 The fear of producing carbon dioxide (CO 2 ) retention and a secondary increase of intracranial pressure sometimes preclude the use of sedation or premedication for the spontaneously breathing patient in the presence of an intracranial space occupying lesion.…”