A 30-year-old woman is rushed to the emergency department at a major trauma center after a motor vehicle accident. Although in significant pain, she is awake, alert, and able to give a brief history. She states that she was the driver and was wearing a seatbelt. There were no passengers in the car. Her past medical history is significant only for asthma, for which she has been intubated once in the past. She has no allergies to medications. There are multiple lacerations on her face and extremities and a large open fracture of her right femur. An orthopedic surgeon has scheduled immediate operative repair of the femur fracture, and the plastic surgeon wants to suture the facial lacerations at the same time. You decide to intubate the patient for the procedure. What muscle relaxant would you choose? Would you choose the same agent if she had experienced a 30% total body burn in a fire at the time of the accident? What if the past medical history included right-sided hemiparesis of 10 years' duration?
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). Neuromuscular blocking drugs interfere with transmission at the neuromuscular end plate and lack central nervous system activity. These compounds are used primarily as adjuncts during general anesthesia to facilitate endotracheal intubation and optimize surgical conditions while ensuring 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, a spasmolytic 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 derivatives 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 the nicotinic receptors located on the motor end plate. As noted in Chapter 7, the adult NM receptor is composed of five peptides: two alpha peptides, one beta, one gamma, and one delta peptide (...