Linton: Introduction to Medical-Surgical Nursing, 4th Edition

Pharmacology Tutorial

Chapter 9: Skeletal Muscle Relaxants

Skeletal muscle relaxants used in the perioperative period are divided into two categories: neuromuscular blocking agents and spasmolytics (antispasm drugs).
Spasmolytic drugs are categorized as centrally acting and peripherally acting. The spasmolytic drug discussed in this chapter is the peripherally acting drug, dantrolene (Dantrium). Neuromuscular blocking agents are classified as nondepolarizing and depolarizing drugs.

Nondepolarizing drugs prevent acetylcholine from acting at the neuromuscular junction, so muscles remain in a relaxed state. Depolarizing drugs act at the neuromuscular junction to combine with cholinergic receptors to cause muscle contraction but not relaxation, thus preventing further neurocommunication (muscle paralysis preceded by muscle spasms). The nondepolarizing drug discussed in this chapter is tubocurarine (Tubocuraine) and the depolarizing agent is succinylcholine (Anectine). 

TUBOCURARINE (TUBOCURAINE)

Action
Tubocurarine is a component of curare, a neuromuscular blocking agent extracted from certain plants found in the Amazonian rain forest. It is an acetylcholine antagonist that competes for the cholinergic receptor sites at the neuromuscular junction. This antagonism causes a decrease in the response of the muscle to acetylcholine, resulting in relaxed (flaccid) paralysis. Tubocurarine has significant histamine-releasing properties, and no known effect on intellectual functions, consciousness, or pain threshold. The drug does not cross the blood-brain barrier and has no effect in the CNS. For this reason, anesthesia is begun before neuromuscular blockade is started, to prevent the unanesthetized patient from having the frightening experience of paralysis and inability to breathe. The neuromuscular blocking action of tubocurarine may be reversed with anticholinesterases such as neostigmine (Prostigmin), pyridostigmine (Mestinon), and edrophonium (Tensilon), which prevent the normal breakdown of acetylcholine at the neuromuscular junction, leading to an accumulation of the neurotransmitter and return of muscle stimulation.

Uses
•	Produce skeletal muscle relaxation as adjunct to general anesthesia
•	Facilitate endotracheal intubation and mechanical ventilation
•	As intensive care unit sedation to minimize the patient’s movements to conserve energy or reduce agitation that may increase intracranial pressure (another nondepolarizing drug, pancuronium [Pavulon], may also be used).
•	Prevent trauma during convulsive therapy
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•	Reduce intensity of muscle contractions in tetanus
•	Diagnose myasthenia gravis

Side and Adverse Effects
•	Pressure ulcers may result from prolonged immobility and paralysis.
•	Respiratory muscle paralysis requires assisted ventilation until drug effects have worn off.
•	Vasodilation due to relaxation of arterial muscles may cause flushing, hypotension, bradycardia, or tachycardia, or worsening of a preexisting heart condition.
•	Relaxation of gastrointestinal tract with decreased muscle tone and motility may lead to vomiting, regurgitation, aspiration.
•	Histamine release may cause wheezing and bronchospasm.
•	If used with a general anesthetic agent, malignant hyperthermia may occur (rare, potentially fatal reaction characterized by sudden, unexpected hyperthermia (temperature > 104 F), severe muscle spasms, carbon dioxide retention, cyanosis, and metabolic acidosis).

Interactions
Drugs that increase the action of tubocurarine include skeletal muscle relaxants, aminoglycosides, inhalation anesthetics, ketamine, quinine derivatives, polymyxin B, clindamycin, amphotericin B, diuretics, procainamide, and verapamil. Drugs that may decrease the effectiveness of tubocurarine include carbamazepine, hydantoins (e.g., phenytoin [Dilantin]), and theophyllines.

Contraindications
Tubocurarine is contraindicated for persons with conditions that may be made worse by histamine release and vasodilation such as asthma, bronchospasm, hypotension, and cardiac disease, as well as for those with hyperthermia. Cautious use is indicated in patients with pulmonary disease or lung cancer, dehydration, electrolyte or acid-base imbalance, decreased renal function, or myasthenia gravis. Hypothermia may decrease the action or duration of tubocurarine.

Nursing Actions
•	Obtain patient history regarding drug/food allergies and renal, hepatic, cardiovascular, or respiratory diseases. Determine personal or family history of malignant hyperthermia.
•	Perform a predrug administration physical assessment including vital signs, state of hydration, weight, reflexes and muscle tone, and breath sounds.
•	 Assess baseline electrolyte values and renal and hepatic status.
•	Emergency equipment for endotracheal intubation, mechanical ventilation, and oxygen should be immediately available. An anticholinesterase drug such as neostigmine (Prostigmin) is used to reverse the effects of tubocurarine. 
•	Know the sequence of muscle paralysis: jaw muscles, eyelid muscles and other muscles of head and neck, limbs, intercostals and diaphragm, abdomen, and trunk. Facial and diaphragm muscles are first to recover, followed in order by legs, arms, shoulder girdle, trunk, larynx, hands and feet, and pharynx. Muscle function usually returns within 90 minutes. 
•	Monitor vital signs closely and keep airway clear of secretions following administration of the drug.
•	Perform frequent skin assessments and change patient’s position frequently if paralysis is prolonged.
•	Understand that patients may experience sore muscles, constipation, difficulty voiding, and dizziness upon arising. 
•	Remember that professional demeanor is very important with patients who have received neuromuscular blocking agents: they are paralyzed but can think and hear.

SUCCINYLCHOLINE (ANECTINE)

Action and Uses
Succinylcholine is a depolarizing neuromuscular blocker that works by causing the muscle cell membrane to become excited (depolarize), leading to rapid muscle contractions followed by flaccid (relaxed) paralysis. Because of these rapid muscle contractions, patients often experience postoperative muscle pain. Succinylcholine is used to produce skeletal muscle relaxation as adjunct to general anesthesia, to facilitate endotracheal intubation and endoscopy, to increase pulmonary compliance in mechanical ventilation, and to reduce intensity of muscle contractions during convulsive therapy. The use of succinylcholine as general anesthesia adjunct or during long-term mechanical ventilation has, for the most part, been replaced by more effective and less toxic neuromuscular blocking agents. Succinylcholine is commonly used during delivery by cesarean section. If repeated doses are required before delivery, the neonate should be closely monitored for apnea and decreased muscle tone.

Side and Adverse Effects
The primary adverse effects of succinylcholine are similar to tubocurarine and result from neuromuscular blockade at all neuromuscular end plates. Prolonged paralysis may lead to decubitus ulcer formation from prolonged immobility. Because of respiratory muscle paralysis with prolonged apnea, assisted ventilation is necessary until the effects of the drug have worn off. Increased intraocular pressure may cause or aggravate glaucoma. Because of the muscle contractions, patients may complain of severe muscle pain that may last for several days after the drug is given. Slight histamine release may contribute to bronchospasms, wheezing, hypotension, and cardiac arrhythmias in susceptible individuals. Succinylcholine, particularly if used with a general anesthetic agent, may cause malignant hyperthermia.

Interactions
A number of drugs may prolong neuromuscular blockade if given concurrently with succinylcholine. Some of the more common ones include aminoglycosides, iodide, halothane, lidocaine, narcotic analgesics, monoamine oxidase inhibitors, phenothiazines, quinine derivatives, procainamide, and propranolol. Digitalis glycosides may increase risk of cardiac arrhythmias. Anticholinesterases (e.g., neostigmine [Prostigmin], pyridostigmine [Mestinon], and edrophonium [Tensilon]) inhibit the action of plasma pseudocholinesterase (necessary to inactivate succinylcholine), thus prolonging neuromuscular blockade. 

Contraindications
The use of succinylcholine is contraindicated for anyone with an individual or family history of malignant hyperthermia. It is also contraindicated for intraocular surgery or for patients with glaucoma. Cautious use is indicated for persons with low serum pseudocholinesterase levels, renal, hepatic, pulmonary, metabolic, or cardiovascular disorders, neuromuscular disease, dehydration, or hyperthermia. Its use may be contraindicated in anyone with hyperkalemia or at risk for hyperkalemia (the intense muscle contractions cause release of potassium into the bloodstream) as well as those with severe burns or trauma. 

Nursing Actions
In addition to those for tubocurarine, nursing actions include:
•	Assess for personal or family history of low pseudocholinesterase levels. Patients at risk for this condition include those with severe burns or trauma, malnutrition or dehydration, severe liver disease, cancer, severe anemia, or myxedema (hypothyroidism). Determine individual or family history of malignant hyperthermia.
•	Know sequence of muscle paralysis: eyelid muscles, jaw, limbs, abdomen, glottis, intercostals, and diaphragm. Recovery generally occurs in reverse order.
•	Inform patients they may experience muscle stiffness and pain for as long as 24 to 72 hours after receiving the drug. They may also experience hoarseness and sore throat.

DANTROLENE (DANTRIUM)

Action
Dantrolene is a peripherally acting muscle relaxant that exerts its effect by direct action within the skeletal muscle fiber. It does not interfere with neuromuscular communication and has no CNS effects. Dantrolene reduces the amount of calcium released from the muscle fibers, thereby causing the muscle contraction (or spasm) to relax. This interference with calcium release from the muscle fibers may prevent an increase in intracellular calcium, which activates the acute muscle spasms of malignant hyperthermia. Dantrolene has no effect on contraction of cardiac or intestinal smooth muscle.

Uses
Intravenous (IV) dantrolene is the drug of choice, with supportive measures such as rapid cooling, for the immediate treatment of malignant hyperthermia. Oral dantrolene may be used 2 to 3 days preoperatively as prophylaxis for patients with an individual or family history of malignant hyperthermia. Dantrolene may be given postoperatively for 1 to 3 days following an occurrence of malignant hyperthermia to prevent recurrence of symptoms. Other uses include symptomatic treatment of skeletal muscle spasms secondary to spinal cord injury, stroke, cerebral palsy, and multiple sclerosis.

Side and Adverse Effects
The most common side effect is muscle weakness sufficient to affect overall functional capacity of the patient. This may be manifested by symptoms of drooling, drowsiness, slurred speech, dizziness, malaise, and fatigue. More serious adverse effects include potentially fatal hepatic necrosis (especially in women older than 35 years old and taking estrogens), seizures, erratic blood pressure, and pleural effusion with pericarditis. Gastrointestinal side effects include diarrhea, bleeding, anorexia, abdominal cramps, and difficulty swallowing. Diarrhea is usually transient, but if severe, the drug may have to be withheld. IV dantrolene may cause edema and thrombophlebitis. With the possible exception of edema and thrombophlebitis at the IV site, these side effects are not common during acute treatment of malignant hyperthermia.

Interactions
Concurrent use of dantrolene with alcohol or other CNS depressants may cause CNS depression. Verapamil and other calcium-channel blockers increase risk of ventricular fibrillation and cardiovascular collapse (from hyperkalemia). Women older than age 35 who are taking estrogens and dantrolene concurrently are at greater risk for hepatotoxicity (mechanism of action unknown). With the exception of verapamil and the potential for hyperkalemia, these interactions do not usually occur during acute treatment of malignant hyperthermia.

Contraindications
There are no contraindications to the use of dantrolene as acute treatment or prevention of malignant hyperthermia. Cautious use is indicated in patients with preexisting neuromuscular disease with respiratory depression, because there is an increased risk of perioperative complications if these patients are receiving dantrolene for prevention of malignant hyperthermia. Long-term use of dantrolene is contraindicated in patients who rely on spasticity to maintain upright posture and balance. Cautious long-term use is indicated for persons with impaired cardiac or respiratory function and for women older than age 35.

Nursing Actions
•	Assess patient for personal or family history of malignant hyperthermia.
•	Avoid IV extravasation (infiltration into the tissue) to prevent tissue necrosis. Monitor IV site frequently.
•	During IV infusion, monitor vital signs, electrocardiogram, and serum electrolytes.