RT Book, Section A1 Jackson, Sam A2 Olson, Kent R. A2 Anderson, Ilene B. A2 Benowitz, Neal L. A2 Blanc, Paul D. A2 Clark, Richard F. A2 Kearney, Thomas E. A2 Kim-Katz, Susan Y. A2 Wu, Alan H. B. SR Print(0) ID 1174607502 T1 NEUROMUSCULAR BLOCKERS T2 Poisoning & Drug Overdose, 7e YR 2018 FD 2018 PB McGraw-Hill Education PP New York, NY SN 9780071839792 LK accessmedicine.mhmedical.com/content.aspx?aid=1174607502 RD 2024/10/11 AB PharmacologyNeuromuscular blocking agents produce skeletal muscle paralysis by inhibiting the action of acetylcholine at the neuromuscular junction (NMJ). Depolarizing agents (succinylcholine; Table III–12) depolarize the motor end plate and block recovery; transient muscle fasciculations occur with the initial depolarization. Nondepolarizing agents (atracurium, pancuronium, and others; see Table III–12) competitively block the action of acetylcholine at the motor end plate, preventing depolarization. Therefore, with nondepolarizing agents, no initial muscle fasciculations occur and a flaccid paralysis is produced.The neuromuscular blockers produce complete muscle paralysis with no depression of CNS function (they are positively charged and water-soluble compounds that do not cross the brain-blood barrier rapidly). Thus, patients who are conscious will remain awake but be unable to move, and patients with status epilepticus may continue to have seizure activity despite paralysis. Furthermore, the neuromuscular blockers do not relieve pain or anxiety and have no sedative or amnestic effects.Succinylcholine produces the most rapid onset of neuromuscular blockade. After intravenous administration, total paralysis ensues within 30-60 seconds and lasts 10-20 minutes. It is hydrolyzed rapidly by pseudocholinesterase, an enzyme present in the vascular compartment but not at the NMJ. Therefore, a relatively small fraction of the administered dose reaches the site of action, and diffusion from the NMJ back into the intravascular space determines metabolism. Larger (1.5 mg/kg IV based on total body weight in adults) rather than smaller doses should be used to achieve optimal paralysis during rapid-sequence intubation (RSI).Rocuronium, a nondepolarizing agent, also has a rapid onset of effect when used at an RSI dose of 1 mg/kg IV (based on ideal body weight) in adults. However, the duration of the blockade (20-90 minutes) is considerably longer than that of succinylcholine. Sugammadex, a specific and rapid reversal agent for rocuronium and vecuronium, has recently received FDA approval for use in adult patients undergoing surgery. The utility of this agent in the patient who requires emergent intubation is not clear.The onset and duration of several other neuromuscular blockers are described in Table III–12.IndicationsNeuromuscular blockers are used to abolish excessive muscular activity, rigidity, or peripheral seizure activity when continued muscle activity may produce or aggravate rhabdomyolysis, mechanical injury, or hyperthermia. Their primary indication is to improve the view of the larynx and other relevant anatomy during endotracheal intubation (see II. B, below). They are also employed when excessive muscular movement may place the patient (or others) at risk for injury.Drug overdoses involving stimulants (eg, amphetamines, cocaine, phencyclidine, monoamine oxidase inhibitors) or strychnine.Tetanus. Nondepolarizing agents should be chosen because infection with Clostridium species can predispose patients to pathologic hyperkalemia induced by the use of succinylcholine.Hyperthermia associated with muscle rigidity or hyperactivity (eg, status epilepticus, neuroleptic malignant syndrome, or serotonin syndrome). Note: In susceptible patients, malignant hyperthermia can be triggered by succinylcholine (see discussion under "adverse effects").In intubated patients, partial or complete neuromuscular blockade may facilitate improved patient-ventilator synchrony and enhanced gas exchange and lower the risk for barotrauma.Suspected or verified cervical spine injury, or any setting in which there is increased intracranial pressure (eg, intracranial hemorrhage, hepatic ...