Pharmacodynamics of the 1R cis -1'R cis isomer of atracurium (51W89) in health and chronic renal failure

Abstract

We have studied the pharmacodynamics of the 1R cis-1'R cis isomer of atracurium (51W89) in 15 healthy subjects and in 17 patients with chronic renal failure using a bolus dose of 51W89 0.1 mg kg-1 (2 x ED95). Fifteen patients with normal renal function were investigated also using an approximately equipotent dose of atracurium (0.4 mg kg-1). The compound surface action potential of the adductor pollicis muscle, in response to train-of-four stimulation of the ulnar nerve at the wrist, was recorded until recovery of the height of the first response of the train-of-four compared with baseline (T1:T0) had reached at least 85% and the train-of-four ratio (T4:T1) at least 80%. In the healthy and renal failure patients who received 51W89, there were no significant differences in any of the onset or recovery variables except for the time to 90% depression of T1:T0, which was longer in patients with renal failure (mean 3.7 min vs 2.4 min; P < 0.05). Of the healthy patients who were given either 51W89 or atracurium, there were no significant differences in the onset data, except for time to maximum block, which was longer in the 51W89 group (mean 7.7 min vs 6.2 min; P < 0.01). The mean times to 10%, 25%, 50% and 75% recovery of T1:T0 and the time for T4:T1 > 70% were significantly longer in patients receiving 51W89.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular blocking effects and train‐of‐four fade with cisatracurium: comparison with other nondepolarising relaxants

“…Other reports are, however, conflicting. Whereas Lepage et al [3] observed median clinical duration of action of 0.1 mg.kg ¹1 cisatracurium to be about 9 min shorter than that of 0.5 mg.kg ¹1 of atracurium, Boyd et al found the recovery to be longer with this dose of cisatracurium compared to 0.4 mg.kg ¹1 of atracurium [12]. The differences between cisatracurium and atracurium may have been exaggerated in the study of Boyd et al who used a comparatively lower dose of atracurium [12].…”

Cisatracurium bei Patienten mit eingeschränkter Nierenfunktion

“…Nach unserer Kenntnis liegt bislang nur eine geringe Anzahl von Arbeiten vor, die sich mit der Anwendung von Cisatracurium bei Patienten mit eingeschränkter Nierenfunktion befassen [3,9].…”

“…Vergleicht man diese Ergebnisse mit Angaben über die Mutonsbedingungen lagen nach 2-3 min bei allen Patienten vor. Die Zeiten der 75%igen (63,2 ± 11,1 min vs. 67,1 ± 21,7 min) und 90%igen Spontanerholung (70,6 ± 13,3 min vs. 76,6 ± 23,1 min) waren nahezu unverändert, ebenso der berechnete Erholungsindex (17,3 ± 5,0 min vs. 23,3 ± 11,0 min) [3]. Eine weitere Untersuchung ergab lediglich geringfü-gige Veränderungen der Pharmakodynamik von Cisatracurium bei Nierenkranken [10].…”

Pharmacodynamics of cisatracurium in the intensive care unit: an observational study

“…Because of its pharmacokinetic properties, cisatracurium, a non-depolarizing neuromuscular blocking agent of the benzylisoquinoline family, is a popular choice in the ICU since it is (at physiological pH and temperature) rapidly degraded by Hoffmann elimination, yielding two metabolites without muscle relaxant properties: laudanosine and quaternary monoacrylate. Impaired renal or liver function has little influence on the pharmacokinetics of this drug [2,3]. The volume of distribution of cisatracurium is limited to the extracellular fluid (144 mL.kg -1 ), total plasma clearance is approximately 5.3 mL.min -1 .kg -1 , and the elimination half life is between 22 and 30 minutes [4,5].…”