A 70-kg, 45-year-old single, unrestrained male driver, is involved in a motor vehicle crash. He is rushed to a nearby level 1 trauma center where he is found to have multiple facial fractures, a severe, unstable cervical spine injury, and significant left eye trauma. Further examination of his left eye reveals rupture of his globe. The ophthalmologist requests emergency surgery to repair and save his eye. Because the patient has suffered a recent trauma, you decide to perform a rapid sequence intubation in preparation for the surgical procedure. What muscle relaxant would you use to facilitate tracheal intubation? What is the proper dose for your chosen muscle relaxant? After intravenous infusion of your chosen muscle relaxant, you are unable to adequately visualize the patient’s larynx and vocal cords and cannot successfully pass an endotracheal tube. You switch to mask ventilation but are barely able to mask ventilate the patient, and you become worried that you will soon lose the ability to ventilate at all. Is there a medication that you can give to facilitate rapid return of spontaneous ventilation in this situation?
Drugs that affect skeletal muscle function include two different therapeutic groups: those used during surgical procedures and in the intensive care unit (ICU) to produce muscle paralysis (ie, neuromuscular blockers), and those used to reduce spasticity in a variety of painful conditions (ie, spasmolytics and antispasmodics). Neuromuscular blocking drugs interfere with transmission at the neuromuscular end plate and lack central nervous system (CNS) activity. These compounds are used primarily as adjuncts during general anesthesia to optimize surgical conditions and to facilitate endotracheal intubation in order to ensure adequate ventilation. Drugs in the spasmolytic group have traditionally been called “centrally acting” muscle relaxants and are used primarily to treat chronic back pain and painful fibromyalgic conditions. Dantrolene, an agent that has no significant central effects and is used primarily to treat a rare anesthetic-related complication, malignant hyperthermia, is also discussed in this chapter.
NEUROMUSCULAR BLOCKING DRUGS
During the 16th century, European explorers found that natives in the Amazon Basin of South America were using curare, an arrow poison that produced skeletal muscle paralysis, to kill animals. The active compound, d-tubocurarine, and its modern synthetic analogs have had a major influence on the practice of anesthesia and surgery and have proved useful in understanding the basic mechanisms involved in neuromuscular transmission.
Normal Neuromuscular Function
The mechanism of neuromuscular transmission at the motor end plate is similar to that described for preganglionic cholinergic nerves in Chapter 6. The arrival of an action potential at the motor nerve terminal causes an influx of calcium and release of the neurotransmitter acetylcholine. Acetylcholine then diffuses across the synaptic cleft to activate nicotinic receptors located on the motor end plate, present at a density of 10,000/μm2 in ...