Pharmacokinetics and Pharmacodynamics of Cisatracurium in Young and Elderly Adult Patients

Sorooshian, Shahpoor S.; Stafford, Michael A.; Eastwood, N. B.; Boyd, A. H.; Hull, C.J.; Wright, P. M. C.

doi:10.1097/00000542-199605000-00010

Cited by 91 publications

(36 citation statements)

References 17 publications

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“…recovery profile was found to be similar between two groups. 17 Similar findings were observed by Ornstein E et al 18 In present study the mean clinical duration of action with 0.15 mg/kg was found to be 35.15±4.13 minutes while that with 0.2 mg/kg was found to be 44.42±3.41 minutes which correlates with the findings of previous studies.…”

Section: Hemodynamic Variablessupporting

confidence: 92%

A clinical comparative study of two intubating doses of cis-atracurium during general anaesthesia for gynaecological surgery

Jammar

Pathak

Begum

et al. 2017

Int J Basic Clin Pharmacol

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INTRODUCTIONCisatracurium besilate is a cis-cis isomer (51W89:1R-cis 1'R-cis atracurium), one of the 10 stereoisomers of atracurium that constitutes 15% of the atracurium mixture, an intermediate duration non-depolarising neuromuscular blocking drug. It is about three to four times more potent than atracurium and devoid of cardiovascular side effects in doses of upto 8 times of ED95. The ED95 of cisatracurium is 0.05mg/kg. 1-5The rate limiting step in the degradation of cisatracurium is Hoffmann degradation.(organ independent elimination) to form laudanosine and monoquaternary alcohol. 77% of drug is cleared via Hoffmann degradation which is a ph and temperature dependent process, rest 23% of drug get cleared through organ dependent means, and renal elimination accounts for 16% of this. Hydrolysis by non-specific esterases is not an important pathway for cisatracurium degradation. It is not associated with histamine release in humans. Although the liver and kidneys play only a small role in the excretion of cisatracurium besilate, urinary and hepatic elimination pathways are important for the metabolites of laudanosine. 5-8The total body clearance (CL), steady-state Vd and elimination half-life of cisatracurium besilate in patients with normal organ function are approximately 0.27 to 0.34 L/h/kg (4.7 ml/min/kg), 0.11 to 0.16 L/kg and 22 to 35 minutes, respectively. The volume of distribution (Vd) ABSTRACT Background: Cisatracurium is one of the cis-cis isomer of atracurium (51W89:1R-cis 1'R-cis atracurium) an intermediate duration non-depolarising neuromuscular blocking drug and is devoid of histamine release. However, 2× ED95 dose of cisatracurium does not provide satisfactory intubating condition. The recommended intubating dose of cisatracurium is 3 ×ED95. The objective of this study was to evaluate and compare duration of action, hemodynamic effects and any adverse effects for different doses of cisatracurium. Methods: After Institutional Ethical Committee approval and informed patient consent, 80 patients of ASA I and II in the age group of 20-60 years were selected and included in the study. Patients were divided in two groups of 40 each, group A received intravenously 3×ED95 (0.15 mg/kg) loading dose of cisatracurium and group B received intravenously 4×ED95 (0.2 mg/kg) loading dose of cisatracurium. Results: After induction, MAP and HR shows decrease in both groups but neither statistically nor clinically significant. Better hemodynamic stability and longer duration of action was found in group B compared to group A. No adverse effects noted in both groups. Conclusions: 4×ED95 dose of cisatracurium provides longer duration of action and more stable hemodynamic status than 3×ED95. No associated signs of histamine release were detected clinically.

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Section: Hemodynamic Variablessupporting

confidence: 92%

A clinical comparative study of two intubating doses of cis-atracurium during general anaesthesia for gynaecological surgery

Jammar

Pathak

Begum

et al. 2017

Int J Basic Clin Pharmacol

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“…While the rates of plasma clearance of vecuronium and rocuronium decline dramatically in the elderly, 14 the pharmacokinetic profile of cisatracurium is essentially unaffected by increasing age. 15,16 One could only speculate as to whether or not a comparison of cisatracurium and rocuronium infusions in an older patient population would demonstrate an analogous time-related discrepancy in infusion requirements, as observed in the earlier trial.…”

Section: Discussionmentioning

confidence: 89%

Cumulation characteristics of cisatracurium and rocuronium during continuous infusion

Miller

Wherrett

Hull

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: The dissimilar pharmacokinetic properties of cisatracurium (CIS) and rocuronium (ROC) predict different potential for drug cumulation when these drugs are administered by continuous infusion. A study was therefore undertaken to compare cumulation potential of CIS and ROC during surgical procedures of relatively long duration (2-4 hr). Methods: Sufentanil/propofol-N 2 O anesthesia was administered to 40 ASA I and II adults. In a double-blind protocol, patients were randomly allocated to receive a continuous iv infusion of either CIS or ROC, titrated in progressive increments or decrements as required to achieve and maintain 95 ± 5% depression of the T1 response of the adductor pollicis muscle, using a Datex NMT-100 Relaxograph EMG monitor applied at the wrist. At the end of surgery, 60 µg·kg -1 neostigmine plus 15 µg·kg -1 atropine were administered for reversal. Results: The duration of infusion was 104 ± 33 min in group CIS and 110 ± 23 min in group ROC (P=NS). In both groups, a progressive decrease in potency-adjusted infusion rates was observed after 30 min, then stabilized beyond 60 min. When allowing for an initial period of stabilization, mean potency-adjusted infusion requirements were: CIS 0.81 ± 0.02 µg·kg -1 ·min -1 and ROC 5.58 ± 1.94 µg·kg -1 ·min -1 . There were no differences between groups at any time with regard to potency-adjusted infusion requirements necessary to maintain 90-99% block (P=NS). However, drug costs/hr for maintenance of neuromuscular block were less with CIS ($3.57 ± 0.09) than with ROC ($6.03 ± 0.27), P < 0.001. Conclusion: When adjusted to equipotency, infusion requirements of CIS and ROC vary at similar rates during general anesthesia. Despite pharmacokinetic differences, neither drug demonstrates cumulation for infusion lasting up to 3.5 hr.Objectif : Les propriétés pharmacocinétiques différentes du cisatracurium (CIS) et du rocuronium (ROC) laissent présager un potentiel différent d'accumulation lorsqu'on les administre en perfusion continue. Une étude a donc été menée pour comparer le potentiel d'accumulation de CIS et de ROC pendant des interventions chirurgicales de durée relativement longue (2-4 h). Méthode : Une anesthésie à base de sufentanil/propofol-N 2 O a été administrée à 40 adultes d'état physique ASA I et II. Selon un protocole à double insu, les patients ont été répartis de façon aléatoire et ont reçu une perfusion iv continue de CIS ou de ROC en doses progressives ou dégressives comme l'exigent la réalisation et le maintien d'une dépression de 95 ± 5 % de la réponse à T1 du muscle adducteur du pouce, en utilisant un moniteur Datex NMT-100 Relaxograph EMG appliqué au poignet. À la fin de l'opération, 60 µg·kg -1 de néostigmine et 15 µg·kg -1 d'atropine ont été administrés pour renverser le bloc. Résultats : La perfusion a duré 104 ± 33 min dans le groupe CIS et 110 ± 23 min dans le groupe ROC (P=NS). Dans les deux groupes, une baisse progressive des vitesses de perfusion ajustée en fonction de la puissance a été observée après 30 min, puis stabilisée a...

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“…Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children TUDIES performed both in animals and humans during hypothermic CPB have indicated that hypothermia below 32°C increases sensitivity to vecuronium, 1-5 pancuronium 1,4,6 atracurium, 5,7-9 rocuronium, 10-12 metocurine 13 and doxacurium 14 but not to alcuronium 15,16 or d-tubocurarine. 1,17 Some studies have examined pharmacodynamic parameters only 1,4,5,7,18 but other authors have performed a complete pharmacokinetic-pharmacodynamic study.…”

Section: Methodsmentioning

confidence: 99%

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Withington

Ménard

Harris

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children. Methods:We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (T1 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteadystate during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion.Results: Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean ± SD: 330 ± 42 ng·ml -1 ; 127 ± 27 ng·ml -1 ; P < 0.001); similarly the clearances showed a bimodal distribution (mean ± SD: 5.08 ± 0.94; 11.51 ± 0.2 ml·min -1 ·kg -1 P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05). Conclusion: Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.Objectif: Déterminer l'effet d'une circulation extracorporelle (CEC) avec hypothermie modérée ou profonde sur les paramètres pharmacocinétiques et pharmacodynamiques du vécuronium chez des nourrissons et des enfants.Méthode : Nous avons étudié 12 patients opérés pour cardiopathie congénitale sous anesthésie avec un mélange de narcotique et de protoxyde d'azote. Le blocage neuromusculaire a été maintenu constant (T1 4-10 % avec un élec-tromyographe Datex) en ajustant une perfusion de vécuronium. Les concentrations plasmatiques de vécuronium (Cpss) ont été analysées par chromatographie liquide haute performance (CLHP) afin de définir l'état pseudo-équilibre pendant chacune des étapes pré-CEC, CEC et post-CEC. Des échantillons appariés de sang artériel ont été prélevés à intervalles de 20 min, après au moins 20 min de perfusion constante.Résultats: Neuf cas ont été analysés, âgés de 20 ms et pesant 9 kg en moyenne. Trois patients avaient une hypothermie profonde et six, une modérée. Pendant la pré-CEC, les Cpss se séparent en deux groupes (moyenne ± écart type : 330 ± 42 ng·ml -1 ; 127 ± 27 ng·ml -1 ; P < 0,001); les clairances ont affiché une distribution bimodale (moyenne ± écart type : 5,08 ± 0,94; 11,51 ± 0,2 ml·min -1 ·kg -1 P < 0,001), chez différents patients cependant. Pendant la CEC, cette distribution bimodale a disparu. La vitesse de perfus...

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Pharmacokinetics and Pharmacodynamics of Cisatracurium in Young and Elderly Adult Patients

Abstract: The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.

Cited by 91 publications

References 17 publications

A clinical comparative study of two intubating doses of cis-atracurium during general anaesthesia for gynaecological surgery

A clinical comparative study of two intubating doses of cis-atracurium during general anaesthesia for gynaecological surgery

Cumulation characteristics of cisatracurium and rocuronium during continuous infusion

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

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