Compared Efficacy and Tolerance of the Neuromuscular Blockade Induced by Brand-name (Nimbex®) and Generic (Cisatrex®) of Cisatracurium in Mechanically Ventilated Critically Ill Patients: a Crossover Double-blind Randomized Study

Overview

Journal Pan Afr Med J

Date 2021 Mar 19

PMID 33738034

Authors

Nesrine Fraj

Khaoula Meddeb

Abdelbaki Azouzi

Sana Romdhani

Helmi Ben Saad

Mohamed Boussarsar

Affiliations

Soon will be listed here.

Abstract

Introduction: use of generic drugs is common. However, there is still concern among patients and physicians that brand name drugs are more efficient. The aim of the study was to compare efficacy and tolerance between two forms of cisatracurium: brand name versus generic name.

Methods: it´s a crossover, randomized, double-blind physiological trial. Patients admitted for hypoxemic acute respiratory failure with PaO2/FIO2 < 200mmHg despite optimized ventilation and sedation thus requiring non-depolarizing neuromuscular blocking agents (NMBAs), were enrolled. Patients received consecutively, in a random order, cisatracurium brand name (Nimbex®) and generic (Cisatrex®) over two-hour period separated by one-hour washout period. Neuromuscular function was monitored by a calibrated train-of-four (TOF) stimulation device. Paralysis time delay to reach TOF of 2/4, recovery kinetics and tolerance were monitored. The number needed to demonstrate a significant difference in time delays to reach a TOF of 2/4 between the two forms of cisatracurium was estimated at 22 patients.

Results: twenty-two patients were included. Eight (36.4%) had acute respiratory distress syndrome; 8(36.4%), acute exacerbation of chronic obstructive pulmonary disease and 3(13.6%), status asthmaticus. Median [IQR] SAPS II at admission, 28.5 [22, 41]. PaO2/FIO2, 121 [81, 156] mmHg. Paralysis time delays were respectively, 80 [50, 112] vs. 87 [65, 115] minutes, in Nimbex® group and Cisatrex® group; (p=0.579). Within the recovery period, the between two-studied drugs´ difference in TOF was at 0.25±0.96; p=0.64. There were no significant hemodynamic differences.

Conclusion: the present study revealed no significant differences in efficacy nor in tolerance between cisatracurium brand name Nimbex® and generic name Cisatrex® in hypoxemic ventilated patients.

References

Ramsay M, Savege T, Simpson B, Goodwin R . Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974; 2(5920):656-9. PMC: 1613102. DOI: 10.1136/bmj.2.5920.656. View

Bouju P, Tadie J, Barbarot N, Letheulle J, Uhel F, Fillatre P . Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study. Ann Intensive Care. 2017; 7(1):10. PMC: 5247382. DOI: 10.1186/s13613-017-0234-0. View

Shrank W, Liberman J, Fischer M, Girdish C, Brennan T, Choudhry N . Physician perceptions about generic drugs. Ann Pharmacother. 2011; 45(1):31-8. DOI: 10.1345/aph.1P389. View

Warr J, Thiboutot Z, Rose L, Mehta S, Burry L . Current therapeutic uses, pharmacology, and clinical considerations of neuromuscular blocking agents for critically ill adults. Ann Pharmacother. 2011; 45(9):1116-26. DOI: 10.1345/aph.1Q004. View

Szakmany T, Woodhouse T . Use of cisatracurium in critical care: a review of the literature. Minerva Anestesiol. 2014; 81(4):450-60. View

Payen J, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou J . Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007; 106(4):687-95. DOI: 10.1097/01.anes.0000264747.09017.da. View

Groetzinger L, Rivosecchi R, Kane-Gill S, Donahoe M . Association Between Train-of-Four Values and Gas Exchange Indices in Moderate to Severe Acute Respiratory Distress Syndrome. Ann Pharmacother. 2016; 50(12):1009-1015. DOI: 10.1177/1060028016664111. View

Lagneau F, Dhonneur G, Plaud B, Mantz J, Gillart T, Duvaldestin P . A comparison of two depths of prolonged neuromuscular blockade induced by cisatracurium in mechanically ventilated critically ill patients. Intensive Care Med. 2002; 28(12):1735-41. DOI: 10.1007/s00134-002-1508-y. View

Baumann M, McAlpin B, Brown K, Patel P, Ahmad I, Stewart R . A prospective randomized comparison of train-of-four monitoring and clinical assessment during continuous ICU cisatracurium paralysis. Chest. 2004; 126(4):1267-73. DOI: 10.1378/chest.126.4.1267. View

10.

Hassali M, Wong Z, Alrasheedy A, Saleem F, Mohamad Yahaya A, Aljadhey H . Perspectives of physicians practicing in low and middle income countries towards generic medicines: a narrative review. Health Policy. 2014; 117(3):297-310. DOI: 10.1016/j.healthpol.2014.07.014. View

11.

Dieye E, Minville V, Asehnoune K, Conil C, Georges B, Cougot P . Pharmacodynamics of cisatracurium in the intensive care unit: an observational study. Ann Intensive Care. 2014; 4(1):3. PMC: 3996108. DOI: 10.1186/2110-5820-4-3. View

12.

Gainnier M, Roch A, Forel J, Thirion X, Arnal J, Donati S . Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2004; 32(1):113-9. DOI: 10.1097/01.CCM.0000104114.72614.BC. View

13.

Thilen S, Bhananker S . Qualitative Neuromuscular Monitoring: How to Optimize the Use of a Peripheral Nerve Stimulator to Reduce the Risk of Residual Neuromuscular Blockade. Curr Anesthesiol Rep. 2016; 6:164-169. PMC: 4963456. DOI: 10.1007/s40140-016-0155-8. View

14.

Plaud B, Baillard C, Bourgain J, Bouroche G, Desplanque L, Devys J . Guidelines on muscle relaxants and reversal in anaesthesia. Anaesth Crit Care Pain Med. 2020; 39(1):125-142. DOI: 10.1016/j.accpm.2020.01.005. View

15.

Newman P, Quinn A, Grounds R, Hunter J, Boyd A, Eastwood N . A comparison of cisatracurium (51W89) and atracurium by infusion in critically ill patients. Crit Care Med. 1997; 25(7):1139-42. DOI: 10.1097/00003246-199707000-00013. View

16.

Hemmerling T, Le N . Brief review: Neuromuscular monitoring: an update for the clinician. Can J Anaesth. 2007; 54(1):58-72. DOI: 10.1007/BF03021901. View

17.

Maclure M . The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol. 1991; 133(2):144-53. DOI: 10.1093/oxfordjournals.aje.a115853. View

18.

Pearson A, Harper N, Pollard B . The infusion requirements and recovery characteristics of cisatracurium or atracurium in intensive care patients. Intensive Care Med. 1996; 22(7):694-8. DOI: 10.1007/BF01709749. View

19.

Prielipp R, Coursin D, Scuderi P, Bowton D, Ford S, Cardenas Jr V . Comparison of the infusion requirements and recovery profiles of vecuronium and cisatracurium 51W89 in intensive care unit patients. Anesth Analg. 1995; 81(1):3-12. DOI: 10.1097/00000539-199507000-00002. View

20.

Diaz L, Zhang J, Heerdt P . Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits. J Am Assoc Lab Anim Sci. 2014; 53(3):283-9. PMC: 4128567. View