Use of neuromuscular blocking medications in critically ill patients
- Karen J Tietze, PharmD
Karen J Tietze, PharmD
- Professor of Clinical Pharmacy
- Philadelphia College of Pharmacy
- University of the Sciences in Philadelphia
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".)
NEUROMUSCULAR TRANSMISSION AND BLOCKADE
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 .
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- NEUROMUSCULAR TRANSMISSION AND BLOCKADE
- DEPOLARIZING AGENTS
- NONDEPOLARIZING AGENTS
- CLINICAL USE
- Selecting an agent
- ADVERSE EFFECTS
- Cardiovascular effects
- Prolonged paralysis
- Neuromuscular dysfunction diagnosed in critical illness
- SUMMARY AND RECOMMENDATIONS