Cumulative dose-response with infusion: a technique to determine neuromuscular blocking potency of atracurium and vecuronium

Abstract

The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. Sixty patients received either single doses (SD) (n = 36), cumulative doses (CD) (n = 12), or CD of vecuronium or atracurium with an infusion (CDI) to replace eliminated or redistributed drug (n = 12). The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and log dose. The potencies obtained with all three methods were within 20% of each other. For vecuronium the ED90 was (mean +/- SE) 0.034 +/- 0.002 (SD), 0.037 +/- 0.003 (CD), and 0.036 +/- 0.003 mg/kg (CDI). For atracurium the ED90 was 0.175 +/- 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium

“…The M M G-based potency estimates, assessed in the current study with an opioid-nitrous oxideoxygen anaesthetic, were consistent with previously determined values for vecuronium [18,19], pan curonium [20] and atracurium [18,19] using the cumulative dose technique.…”

Sensitivity to vecuronium in myasthenia gravis: a dose-response study

“…They concluded that the use of an infusion to compensate for drug lost by redistribution or elimination resulted in the generation of dose-response curves that were indistinguishable from curves obtained with SB methods. Using the CDI technique and integrated EMG monitoring of the first dorsal interosseous muscle, we obtained mean EDso and ED90 values for vecuronium of 19 and 31 p,g.kg -I in normal patients, compared with the values of 23 and 34 I, tg' kg-1 (SB) and 21 and 36 lig-kg -~ (CDI), respectively, reported by Smith et al 8 We employed integrated EMG monitoring of the first dorsal interosseous muscle because this technique is simple to apply and it may be used in patients whose arms are adducted during surgery. Although the evoked adductor pollicis mechanomyogram is the response most commonly monitored, Kopman '4 has reported that the first dorsal interosseous EMG may be used interchangeably with it in determining depth of non-depolarizing neuromuscular blockade.…”

“…Smith et al 8 have introduced a cumulative doseresponse with infusion (CDI) technique to determine the potency of atracurium and vecuronium. They concluded that the use of an infusion to compensate for drug lost by redistribution or elimination resulted in the generation of dose-response curves that were indistinguishable from curves obtained with SB methods.…”

“…5 The cumulative close technique has been shown to underestimate the potency of vecuronium in normal patients, 9-~1 whereas the use of a cumulative dose plus infusion technique provides potency estimates which are similar to those obtained using a single bolus technique. 8 The purpose of the present study was to use a cumulative dose plus infusion technique: (1) to establish the dose-effect relationship for vecuronium in normal patients and patients with myasthenia gravis, and (2) in patients with myasthenia gravis, to determine whether administration of pyridostigmine on the morning of surgery, or chronic corticosteroid therapy, would influence the sensitivity to vecuronium.…”

Dose-response and time-course of the effect of rocuronium bromide during sevoflurane anaesthesia

“…The incremental cumulative dose technique was used to evaluate the dose-response relationship of rocuronium in the current study. Some investigators have found that the cumulative dose technique may underestimate the potency of neuromuscular blocking agents with rapid distribution and elimination [19][20][21][22]. However, administration of rocuronium was consistent throughout the study and the patients were chosen randomly, thus the degree of redistribution would have been similar in the two groups of patients.…”