Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Use of neuromuscular blocking medications in critically ill patients

Karen J Tietze, PharmD
Section Editor
Polly E Parsons, MD
Deputy Editor
Geraldine Finlay, MD


Neuromuscular blocking agents (NMBAs) paralyze skeletal muscles by blocking the transmission of nerve impulses at the myoneural junction. NMBAs do not have sedative, amnestic, or analgesic properties and do not prevent muscles from contracting if directly stimulated. These drugs may be useful in the intensive care unit (ICU) to improve patient-ventilator synchrony, enhance gas exchange, and diminish the risk of barotrauma. They can also be employed to reduce muscle oxygen consumption, facilitate short procedures, prevent unwanted movements in patients with increased intracranial pressure, and facilitate treatment of acute neurologic conditions such as tetanus (table 1) [1-4].

The mechanism of action, clinical use, and potential adverse effects of NMBAs will be discussed here. Adequate sedation and analgesia, which are essential prior to initiating therapy with NMBAs, are discussed separately. (See "Sedative-analgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal" and "Pain control in the critically ill adult patient".)


The neuromuscular junction consists of the nerve terminal, the synaptic cleft, and the motor endplate. Acetylcholine (ACh) is released into the synaptic cleft when nerve impulses reach the nerve terminal and diffuses across the synaptic cleft to the motor endplate. Attachment of ACh to the nicotinic (not muscarinic) receptors on skeletal muscle causes a conformational change in the receptor that increases myocyte cell membrane permeability to sodium, potassium, chloride, and calcium ions and releases calcium from the sarcoplasmic reticulum, leading to transmission of an action potential [5,6]. Depolarization terminates when ACh unbinds from the receptor. ACh either diffuses back into the nerve terminal or is broken down by acetylcholinesterase.

Neuromuscular blocking agents (NMBAs) are structurally related to ACh and act by interfering with the binding of ACh to the motor endplate. They are divided into depolarizing or nondepolarizing agents based upon their mechanism of action [2,6-8].

Depolarizing NMBAs bind to cholinergic receptors on the motor endplate, causing initial depolarization on the endplate membrane followed by blockade of neuromuscular transmission. Because calcium is not resequestered in the sarcoplasmic reticulum, muscles are refractory to repeat depolarization until depolarizing NMBAs diffuse from the receptor to the circulation and are hydrolyzed by plasma pseudocholinesterase [5].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Feb 16, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Elliot JM, Bion JF. The use of neuromuscular blocking drugs in intensive care practice. Acta Anaesthesiol Scand Suppl 1995; 106:70.
  2. Wheeler AP. Sedation, analgesia, and paralysis in the intensive care unit. Chest 1993; 104:566.
  3. Berger I, Waldhorn RE. Analgesia, sedation and paralysis in the intensive care unit. Am Fam Physician 1995; 51:166.
  4. Isenstein DA, Venner DS, Duggan J. Neuromuscular blockade in the intensive care unit. Chest 1992; 102:1258.
  5. Hanson CW 3rd. Pharmacology of neuromuscular blocking agents in the intensive care unit. Crit Care Clin 1994; 10:779.
  6. Topulos GP. Neuromuscular blockade in adult intensive care. New Horiz 1993; 1:447.
  7. Durbin CG Jr. Neuromuscular blocking agents and sedative drugs. Clinical uses and toxic effects in the critical care unit. Crit Care Clin 1991; 7:489.
  8. Prielipp RC, Coursin DB. Applied pharmacology of common neuromuscular blocking agents in critical care. New Horiz 1994; 2:34.
  9. Martyn JA, Fagerlund MJ, Eriksson LI. Basic principles of neuromuscular transmission. Anaesthesia 2009; 64 Suppl 1:1.
  10. Hunter JM. New neuromuscular blocking drugs. N Engl J Med 1995; 332:1691.
  11. Whittaker M. Plasma cholinesterase variants and the anaesthetist. Anaesthesia 1980; 35:174.
  12. Yentis SM. Suxamethonium and hyperkalaemia. Anaesth Intensive Care 1990; 18:92.
  13. MacLennan N, Heimbach DM, Cullen BF. Anesthesia for major thermal injury. Anesthesiology 1998; 89:749.
  14. Gronert GA. Succinylcholine hyperkalemia after burns. Anesthesiology 1999; 91:320.
  15. Fisher DM, Canfell PC, Fahey MR, et al. Elimination of atracurium in humans: contribution of Hofmann elimination and ester hydrolysis versus organ-based elimination. Anesthesiology 1986; 65:6.
  16. Chapple DJ, Miller AA, Ward JB, Wheatley PL. Cardiovascular and neurological effects of laudanosine. Studies in mice and rats, and in conscious and anaesthetized dogs. Br J Anaesth 1987; 59:218.
  17. Grigore AM, Brusco L Jr, Kuroda M, Koorn R. Laudanosine and atracurium concentrations in a patient receiving long-term atracurium infusion. Crit Care Med 1998; 26:180.
  18. Caldwell, JE, Miller, RD. Muscle relaxants in the intensive care unit. Hosp Physician 1996; 9:11.
  19. 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; 73:741.
  20. Devlin JC, Head-Rapson AG, Parker CJ, Hunter JM. Pharmacodynamics of mivacurium chloride in patients with hepatic cirrhosis. Br J Anaesth 1993; 71:227.
  21. Phillips BJ, Hunter JM. Use of mivacurium chloride by constant infusion in the anephric patient. Br J Anaesth 1992; 68:492.
  22. Stoops CM, Curtis CA, Kovach DA, et al. Hemodynamic effects of mivacurium chloride administered to patients during oxygen-sufentanil anesthesia for coronary artery bypass grafting or valve replacement. Anesth Analg 1989; 68:333.
  23. Vandenbrom RH, Wierda JM. Pancuronium bromide in the intensive care unit: a case of overdose. Anesthesiology 1988; 69:996.
  24. Khuenl-Brady KS, Reitstätter B, Schlager A, et al. Long-term administration of pancuronium and pipecuronium in the intensive care unit. Anesth Analg 1994; 78:1082.
  25. Basta SJ, Savarese JJ, Ali HH, et al. Histamine-releasing potencies of atracurium, dimethyl tubocurarine and tubocurarine. Br J Anaesth 1983; 55 Suppl 1:105S.
  26. Scott RP, Savarese JJ, Basta SJ, et al. Atracurium: clinical strategies for preventing histamine release and attenuating the haemodynamic response. Br J Anaesth 1985; 57:550.
  27. Segredo V, Caldwell JE, Matthay MA, et al. Persistent paralysis in critically ill patients after long-term administration of vecuronium. N Engl J Med 1992; 327:524.
  28. Partridge BL, Abrams JH, Bazemore C, Rubin R. Prolonged neuromuscular blockade after long-term infusion of vecuronium bromide in the intensive care unit. Crit Care Med 1990; 18:1177.
  29. Farquhar-Mayes A. Ethical considerations in the use of neuromuscular blockades. Crit Care Nurs Q 1995; 18:13.
  30. Murray MJ, DeBlock H, Erstad B, et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med 2016; 44:2079.
  31. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017; 45:486.
  32. Rhoney DH, Murry KR. National survey of the use of sedating drugs, neuromuscular blocking agents, and reversal agents in the intensive care unit. J Intensive Care Med 2003; 18:139.
  33. Mehta S, Burry L, Fischer S, et al. Canadian survey of the use of sedatives, analgesics, and neuromuscular blocking agents in critically ill patients. Crit Care Med 2006; 34:374.
  34. Rose JB, Theroux MC, Katz MS. The potency of succinylcholine in obese adolescents. Anesth Analg 2000; 90:576.
  35. Pühringer FK, Keller C, Kleinsasser A, et al. Pharmacokinetics of rocuronium bromide in obese female patients. Eur J Anaesthesiol 1999; 16:507.
  36. Pühringer FK, Khuenl-Brady KS, Mitterschiffthaler G. Rocuronium bromide: time-course of action in underweight, normal weight, overweight and obese patients. Eur J Anaesthesiol Suppl 1995; 11:107.
  37. Kirkegaard-Nielsen H, Helbo-Hansen HS, Lindholm P, et al. Anthropometric variables as predictors for duration of action of atracurium-induced neuromuscular block. Anesth Analg 1996; 83:1076.
  38. Schwartz AE, Matteo RS, Ornstein E, et al. Pharmacokinetics and pharmacodynamics of vecuronium in the obese surgical patient. Anesth Analg 1992; 74:515.
  39. Suzuki T, Masaki G, Ogawa S. Neostigmine-induced reversal of vecuronium in normal weight, overweight and obese female patients. Br J Anaesth 2006; 97:160.
  40. Ellender, PJ. The use of neuromuscular blocking agents in ICU patients. Hosp Pharm 1994; 29:36.
  41. Dulin PG, Williams CJ. Monitoring and preventive care of the paralyzed patient in respiratory failure. Crit Care Clin 1994; 10:815.
  42. Rudis MI, Guslits BG, Zarowitz BJ. Technical and interpretive problems of peripheral nerve stimulation in monitoring neuromuscular blockade in the intensive care unit. Ann Pharmacother 1996; 30:165.
  43. Kleinpell R, Bedrosian C, McCormick L, et al. Use of peripheral nerve stimulators to monitor patients with neuromuscular blockade in the ICU. Am J Crit Care 1996; 5:449.
  44. Shapiro BA, Warren J, Egol AB, et al. Practice parameters for sustained neuromuscular blockade in the adult critically ill patient: an executive summary. Society of Critical Care Medicine. Crit Care Med 1995; 23:1601.
  45. Rudis MI, Sikora CA, Angus E, et al. A prospective, randomized, controlled evaluation of peripheral nerve stimulation versus standard clinical dosing of neuromuscular blocking agents in critically ill patients. Crit Care Med 1997; 25:575.
  46. Strange C, Vaughan L, Franklin C, Johnson J. Comparison of train-of-four and best clinical assessment during continuous paralysis. Am J Respir Crit Care Med 1997; 156:1556.
  47. Baumann MH, McAlpin BW, Brown K, et al. A prospective randomized comparison of train-of-four monitoring and clinical assessment during continuous ICU cisatracurium paralysis. Chest 2004; 126:1267.
  48. Sessler CN. Train-of-four to monitor neuromuscular blockade? Chest 2004; 126:1018.
  49. Shalansky, KF, Shalansky, SJ. Selection and monitoring of muscle relaxants during mechanical ventilation. Can J Hosp Pharm 1992; 45:47.
  50. Schaller SJ, Fink H. Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. Core Evid 2013; 8:57.
  51. Welliver M, Cheek D, Osterbrink J, McDonough J. Worldwide experience with sugammadex sodium: implications for the United States. AANA J 2015; 83:107.
  52. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm477512.htm (Accessed on December 17, 2015).
  53. Raps EC, Bird SJ, Hansen-Flaschen J. Prolonged muscle weakness after neuromuscular blockade in the intensive care unit. Crit Care Clin 1994; 10:799.
  54. Price DR, Mikkelsen ME, Umscheid CA, Armstrong EJ. Neuromuscular Blocking Agents and Neuromuscular Dysfunction Acquired in Critical Illness: A Systematic Review and Meta-Analysis. Crit Care Med 2016; 44:2070.
  55. Phillips MS, Williams RL. Improving the safety of neuromuscular blocking agents: a statement from the USP Safe Medication Use Expert Committee. Am J Health Syst Pharm 2006; 63:139.