Case 4 - Muscle Relaxants

Question 1

A 47-year-old patient is undergoing the clipping of an intracranial aneurysm of the anterior communicating artery. The surgery is being performed under a microscope, so even the smallest movement by the patient could have devastating consequences.

Question

How can the patient be protected and the surgery allowed to proceed?

Answer 1

Best method to protect the patient: Neuromuscular blockade leading to muscle paralysis

During intracranial aneurysm surgery, the patient is positioned with the head stabilized by pins. Moreover, the surgery is exquisitely delicate and typically performed under a microscope. Because of the necessity of keeping the patient still, she will receive vecuronium, a nondepolarizing neuromuscular blocker. This surgery usually takes many hours. However, at the end of the procedure, the patient’s paralysis will be reversed, she will be allowed to awaken, and will be extubated to allow her participation in a neurological examination.

Question 2

What is the mechanism of action of neuromuscular blockers?

Answer 2

Neuromuscular blockers (NMB) or muscle relaxants are intravenous drugs that are used for muscle relaxation and paralysis by interrupting the transmission of action potentials at the neuromuscular junction. They act predominantly by binding post-junctional nicotinic receptors on skeletal muscle, thereby blocking the nerve depolarization caused by acetylcholine.

Question 3

What route is neuromuscular blockers/muscule relaxants given through?

Answer 3

Intravenous

Question 4

What are the indications for neuromuscular blockade?

Answer 4

To facilitate tracheal intubation

To optimize surgical conditions, for example, during intra-abdominal, intrathoracic, and intracranial procedures

To optimize ventilation in a patient who requires controlled mechanical ventilation

Basically, when we want to keep a patient very still.

Question 5

What is a very important consideration with using neuromuscular junction blockers in a procedure?

Answer 5

NMBs only produce paralysis; they have no intrinsic anesthetic or sedative effects. Paralysis with insufficient anesthesia or sedation is an unpleasant and frightening event. In rare cases, surgery has continued in paralyzed patients who are insufficiently anesthetized, leading to “awareness under anesthesia.”

Question 6

What are the two classes of muscle relaxants/NMBs?

Answer 6

NMBs are divided into two classes: depolarizing, and nondepolarizing.

Question 7

What is the only depolarizing NMB? How does it work?

Answer 7

The only depolarizing NMB is succinylcholine.Succinylcholine acts at the nicotinic receptor to produce an initial depolarization manifested by transient skeletal muscle fasciculations, later followed by repolarization and paralysis

Question 8

What is the important clinical consideration for using succinylcholine as a muscle relaxant/NMB?

Answer 8

Since succinylcholine is a depolarizing muscle relaxant, it causes the release of potassium in a manner similar to that observed when a neuron actually fires. Thus, succinylcholine normally increases plasma K+ level from 0.5 to 1.0 mEq. Thus in a patient with pre-existent hyperkalemia, the use of succinylcholine may place the patient at risk for cardiac arrhythmias. The succinylcholine-induced release of potassium is exaggerated in patients with lower motor neuron disease, third-degree burns, long-term immobility, Duchene muscular dystrophy, and rarely, intra-abdominal sepsis. In these clinical settings, its use can cause a hyperkalemic arrest. Succinylcholine has also been associated with painful myalgias in the postoperative period, and it is a potent trigger for malignant hyperthermia.

Question 9

How is succinylcholine metabolized? How is this clinically relevant?

Answer 9

Succinylcholine is metabolized by plasma pseudocholinesterase.

Genetics predispose some families to have either defective, or a deficient amount of pseudocholinesterase isoenzymes in plasma. In these individuals, the duration of action of succinylcholine may be prolonged, and can range from a couple of hours to many hours, depending on the enzymatic alterations. To ensure that pseudocholinesterase deficiency is diagnosed if present, patients are allowed to recover function following succinylcholine administration, before a nondepolarizing muscle relaxant is administered.

Question 10

What is succinylcholine mainly used for?

Answer 10

Succinylcholine has a rapid onset, and short duration making it an ideal agent for intubation

Question 11

What is the mechanism of action of nondepolarizing muscle relaxants?

Answer 11

Nondepolarizing muscle relaxants represent the second class of NMBs, which compete with acetylcholine for the nicotinic receptor resulting in a competitive inhibition of blockade. While they act primarily at postsynaptic receptors, some, such as pancuronium, act at pre-junctional receptors as well.

Question 12

What are the four nondepolarizing blockers and how are they classified?

Answer 12

The four nondepolarizing blockers in use today are distinguished by their duration of action and methods of excretion.

Three of the four competitive (nondepolarizing) agents have an intermediate duration of action (rocuronium, vecuronium, and cisatracurium). Rocuronium is distinguished from the other intermediate agents by its rapid onset of action which is similar to, but not quite as fast, as succinylcholine. One agent (pancuronium) is long-acting.

Question 13

Which nondepolarizing agents are contraindicated in patients with severe liver disease?

Answer 13

Rocuronium and vecuronium are largely metabolized (about 80%) and excreted by the hepatobiliary system. Thus, their duration of action may be prolonged in patients with severe liver disease.

Question 14

Which nondepolarizing agents are contraindicated in patients with end-stage renal failure?

Answer 14

The main hepatic metabolite of vecuronium, 3-desacetyl-vecuronium, is an active metabolite excreted by the kidney. Thus, the duration of vecuronium’s action is also prolonged in patients with end-stage renal failure. Pancuronium’s clearance is about 80% renal, so its elimination may be delayed in patients with severe renal disease.

Question 15

Which nondepolarizing agent is the ideal muscle relaxant for patients with hepatic or renal failure?

Answer 15

Cisatracurium is independently cleared by Hoffman elimination (degradation in plasma at physiologic pH and temperature)

Question 16

How do we know that we have enough neuromuscular blockade?

Answer 16

The degree of neuromuscular blockade has been shown to correlate in a near- linear fashion with the height of the twitch derived from stimulation of the adductor pollicus longus muscle (which governs opposition of the thumb) at 2 Hz. This finding formed the basis for the Train-of-Four monitoring of muscle relaxation measured with a peripheral nerve stimulator. The Train of Four measures the response to four twitches administered over 2 seconds. If the anesthetist can feel the presence of four twitches, then the patient is 75% paralyzed or less. If he/she feels three twitches, then the patient can be up to 85% paralyzed. Two twitches indicate that the patient is 95% paralyzed, one twitch, 99%, and no twitches indicate that the patient is totally paralyzed, or more (meaning that there is an excess in muscle relaxant).

It is important to understand the implications of the two extremes of monitoring with the Train of Four. The first 75% or so of receptors paralyzed are not monitored. Thus, a patient can be paralyzed by 75% and still have all four twitches, similar to someone who is not paralyzed at all. At the other extreme, the absence of twitches gives no information as to the likely duration of the existing blockade. Thus, to measure the degree of relaxation between these two extremes, either one, two, or three twitches must be present. As the patient shows some evidence of recovery of neuromuscular function (three out of four twitches), the anesthetist can cautiously give more muscle relaxant intravenously. Generally the presence of one to three twitches is adequate for surgical relaxation.

Question 17

How do we reverse neuromuscular blockade?

Answer 17

Nondepolarizing neuromuscular blockers are competitive antagonist acetylcholine at the neuromuscular junction. They are reversed by increasing the amount of acetylcholine relative to the NMB, using a peripheral anticholinesterase inhibitor, typically neostigmine, to reclaim the receptor from the blocker. Reversal of the neuromuscular blockade is possible if there is some evidence of spontaneous recovery at the neuromuscular junction, as detected by at least one out of four twitches.

Question 18

What are the side effects of neostigmine? How do we diminish these effects?

Answer 18

Neostigmine has some troublesome cholinergic side effects such as bradycardia, bronchospasm, and an increase in gut motility that reflect the stimulation of muscarinic receptors by increasing acetylcholine concentrations throughout the body. To reduce these untoward effects, glycopyrrolate, an anticholinergic agent, is administered concomitantly with the neostigmine.

Question 19

How can we tell that there is an adequate reversal of neuromuscular blockade?

Answer 19

It is important to note that clinical signs are the best indicators of an adequate reversal of neuromuscular blockade. The patient’s ability to lift the head for 5 seconds, to protrude his or her tongue, and maintain an inspiratory pressure ≥ -21 cm H2O are reliable signs of adequate reversal. The inability to sustain a prolonged muscle movement (such as extending the arm), and the sensation that one is unable to breathe or handle secretions are signs of an inadequate reversal.

Question 20

What are not reliable indicators for adequate reversal of neuromuscular blockade?

Answer 20

Tidal volume respiratory mechanics and the Train-of-Four responses are not reliable indicators for adequate reversal.Next: Clinical Pearls