The Study of Pharmacokinetics and Pharmacodynamics of Cisatracurium

Summary

Pathophysiological changes influenced by multiple factors in critically ill patients, has a significant impact on pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium. In order to understand better and find an appropriate dosing regimen, the purpose of this study is to investigate the PK and PD of a loading dose cisatracurium in critically ill patients. Cisatracurium, nondepolarizing neuromuscular blocking agents (NMBAs), are commonly used in intensive care units because of a lesser effect on hemodynamic parameters and a reduction in mortality rate in ARDS patients. Loading dose recommended in clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient is 0.1-0.2 mg/kg. Then, maintenance dose of 1-3 mcg/kg/min is followed regarding indications, such as ARDS. However, this recommended loading dose might not be adequate in critically ill patients, the study in this specific population might be needed.

Timeline

Start

2017-12-15

Primary completion

2018-08-31

Completion

2018-08-31

Publications

• Background Liu X, Kruger PS, Weiss M, Roberts MS. The pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients with severe sepsis. Br J Clin Pharmacol. 2012 May;73(5):741-9. doi: 10.1111/j.1365-2125.2011.04149.x.
• Background Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, McGee W, McManus C, Meade M, Nix S, Patterson A, Sands MK, Pino R, Tescher A, Arbour R, Rochwerg B, Murray CF, Mehta S. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016 Nov;44(11):2079-2103. doi: 10.1097/CCM.0000000000002027.
• Background Gainnier M, Roch A, Forel JM, Thirion X, Arnal JM, Donati S, Papazian L. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2004 Jan;32(1):113-9. doi: 10.1097/01.CCM.0000104114.72614.BC.
• Background Greenberg SB, Vender J. The use of neuromuscular blocking agents in the ICU: where are we now? Crit Care Med. 2013 May;41(5):1332-44. doi: 10.1097/CCM.0b013e31828ce07c.
• Background Forel JM, Roch A, Marin V, Michelet P, Demory D, Blache JL, Perrin G, Gainnier M, Bongrand P, Papazian L. Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2006 Nov;34(11):2749-57. doi: 10.1097/01.CCM.0000239435.87433.0D.
• Background Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.
• Background Dieye E, Minville V, Asehnoune K, Conil C, Georges B, Cougot P, Fourcade O, Conil JM. Pharmacodynamics of cisatracurium in the intensive care unit: an observational study. Ann Intensive Care. 2014 Feb 11;4(1):3. doi: 10.1186/2110-5820-4-3.
• Background Murray MJ, Cowen J, DeBlock H, Erstad B, Gray AW Jr, Tescher AN, McGee WT, Prielipp RC, Susla G, Jacobi J, Nasraway SA Jr, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists, American College of Chest Physicians. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med. 2002 Jan;30(1):142-56. doi: 10.1097/00003246-200201000-00021. No abstract available.
• Background Welch RM, Brown A, Ravitch J, Dahl R. The in vitro degradation of cisatracurium, the R, cis-R'-isomer of atracurium, in human and rat plasma. Clin Pharmacol Ther. 1995 Aug;58(2):132-42. doi: 10.1016/0009-9236(95)90190-6.
• Background McManus MC. Neuromuscular blockers in surgery and intensive care, Part 1. Am J Health Syst Pharm. 2001 Dec 1;58(23):2287-99. doi: 10.1093/ajhp/58.23.2287.
• Panusitthikorn P, Suthisisang C, Tangsujaritvijit V, Nosoongnoen W, Dilokpattanamongkol P. Pharmacokinetics and pharmacodynamics studies of a loading dose of cisatracurium in critically ill patients with respiratory failure. BMC Anesthesiol. 2022 Jan 22;22(1):32. doi: 10.1186/s12871-022-01571-2.

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Indications