Midazolam-Thiopental Anesthetic Interaction in Patients

Tverskoy, Mark; Fleyshman, G; Bradley, Edwin L.; Kissin, Igor

doi:10.1213/00000539-198804000-00008

Cited by 43 publications

(10 citation statements)

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“…methodology used in our investigation. Using bolus study designs, Tverskoy and colleagues, 3 Short, Galletly and Plummer, 4 Naguib and colleagues, 5 8 van Hemelrijck and colleagues 9 and Kissin and Vinik 10 reported ED 50 values for induction of anaesthesia in the range 2-3 mg kg -1 for thiopental alone, slightly lower than our values (LVCϭ3.7; DFϭ3.8 mg kg -1 ). Short, Galletly and Plummer 4 quoted an 593 'anaesthetic' thiopental ED 50 of 3.6 mg kg -1 (our LRP, 6.9 mg kg -1 ), reduced by half to 1.8 mg kg -1 after premedication with midazolam 0.1 mg kg -1 (our LRP, 6.1 mg kg -1 ; reduction of one-ninth with midazolam 0.05 mg kg -1 ).…”

Section: Discussioncontrasting

confidence: 60%

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points

Wilder‐Smith¹,

Ravussin²,

Décosterd³

et al. 1999

British Journal of Anaesthesia

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We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.v. (group TM, n12) or no midazolam (group T0, n13). ED 50 and ED 95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantly thiopental ED 50 and ED 95 values at all end-points (exception for ED 95 for BUR). Potentiation was greatest for the motor end-point (dropping the infusion bag (DF)) (ED 95 52%, ED 50 23%, median 39%), and smallest for painful stimulation (LRP) (median 18%; ED 50 13%). For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED 50 to ED 95 (LRP 31%, DF 29%). There were no such increases for LVC or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our data suggest that the mechanism of interaction between midazolam premedication and thiopental was different for motor effects or analgesia (DF, LRP) compared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these distinct anaesthetic end-points. Br J Anaesth 1999; 83: 590-5 The use of drug combinations is popular in clinical anaesthetic practice. Combinations can increase the spectrum of action of anaesthesia and reduce side effects by decreasing the required dose of individual drugs by synergism or additive effects. As anaesthesia results from the summation of multiple central nervous system effects, investigations of anaesthetic drug interactions should ideally include multiple end-points relevant to the anaesthetic state. The majority of studies defining drug interactions for anaesthesia have involved i.v. bolus administration. Typically , they provide dose-effect relationships for a single clinical end-point, such as the hypnotic end-point of loss of verbal contact or the eyelash reflex, examined in a fixed time window. Such studies do not generally provide © British Journal of Anaesthesia information on clinically important time elements or allow comparison of interactions at multiple end-points. Infusion induction titration models 1 2 may represent an interesting alternative for the study of drug interactions. They include the clinically important time element, allow easy evaluation and comparison of multiple end-points in one patient and session, and provide clinically relevant results applicable to bolus dosing. 2 Midazolam, as an i.v. premedicant or co-inductant, has been shown to result in hypnotic synergism with thiopental 3 4 during induction of anaesthesia using bolus methodo...

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Section: Discussioncontrasting

confidence: 60%

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points

Wilder‐Smith¹,

Ravussin²,

Décosterd³

et al. 1999

British Journal of Anaesthesia

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“…Several i.v. agents, including thiopentone [1,2], fentanyl [3] and alfentanil [4,5] have been shown to act synergistically when given in combination with midazolam at induction of anaesthesia using the end-point of hypnosis (loss of response to verbal command) to define successful induction. The use of propofol in combination with midazolam has been studied also [6], but the nature of the sedative interactions is not known.…”

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confidence: 99%

Propofol and Midazolam Act Synergistically in Combination

Short

Chui

1991

British Journal of Anaesthesia

198

105

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We have studied interactions between i.v. propofol and midazolam for induction of anaesthesia in 200 unpremedicated female patients undergoing elective gynaecological surgery. Using end-points of "hypnosis" (loss of response to verbal command) and "anaesthesia" (loss of response to a 5-s transcutaneous tetanic stimulus), we determined dose-response curves for propofol and midazolam alone and in combination. For hypnosis, synergistic interaction was found (P less than 0.01), the combination having 1.44 times the potency of the individual agents. Although midazolam failed to produce anaesthesia in the dose range used, the dose of propofol required to produce anaesthesia was reduced by 52% in the presence of midazolam (P less than 0.01). The reduction in arterial pressure at induction was the same for the combination as for the individual agents. The cause of the synergism was not clear, but may have been interaction at CNS GABAA receptors.

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“…have quantitated the degree of synergism between premedication is one by Saarnivara et al (25). midazolam and thiopentone in adult females using However, their study did not include a placebo group an elegant technique of isobolographic analysis (9). who did not receive midazolam.…”

Section: Figurementioning

confidence: 99%

“…Both animal holding area adjacent to the operating rooms. Anaesthesia was induced within 30-60 min of (8) and adult human studies (9) have shown that intravenous midazolam and thiopentone interact midazolam administration. If the anaesthetic induction began more than 60 min after synergistically on induction of anaesthesia.…”

Section: Introductionmentioning

confidence: 99%

Does thiopentone delay recovery in children premedicated with midazolam?

Morley‐Forster

McAllister

Vandenberghe

et al. 1997

Pediatric Anesthesia

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This prospective, randomized trial of paediatric surgical outpatients, premedicated with oral midazolam, was designed to determine if an intravenous thiopentone induction of anaesthesia prolongs postoperative recovery compared to an inhalation induction with halothane. One hundred children, one to ten years of age, undergoing ENT surgical procedures of 30-60 min duration received midazolam 0.5 mg.kg-1 with atropine 0.03 mg.kg-1 and were randomized to either halothane (Group 1, n = 50) or a thiopentone induction (Group 2, n = 50) technique, followed by a standardized anaesthetic-protocol. Time to extubation was significantly greater in the thiopentone group (8.8 +/- 4 min vs 7.1 +/- 3 min, P < 0.05). Patients receiving thiopentone were also more sedated than the halothane group on arrival in the PARR (3.9 +/- 1.5, 3.3 +/- 1.7, respectively P < 0.05), but the differences disappeared after 30 min. Children premedicated with oral midazolam who receive an intravenous thiopentone induction have a slightly prolonged emergence from anesthesia compared to children induced with halothane.

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Midazolam-Thiopental Anesthetic Interaction in Patients

Cited by 43 publications

References 0 publications

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points

Propofol and Midazolam Act Synergistically in Combination

Does thiopentone delay recovery in children premedicated with midazolam?

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