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Chapter: Clinical Anesthesiology: Clinical Pharmacology: Neuromuscular Blocking Agents

Nondepolarizing Muscle Relaxants: General Pharmacological Characteristics

Some variables affect all nondepolarizing muscle relaxants.

General Pharmacological Characteristics

Some variables affect all nondepolarizing muscle relaxants.

A. Temperature

Hypothermia prolongs blockade by decreasing metabolism (eg, mivacurium, atracurium, and cisa-tracurium) and delaying excretion (eg, pancuronium and vecuronium).

B. Acid–Base Balance

Respiratory acidosis potentiates the blockade of most nondepolarizing relaxants and antagonizes its reversal. This could prevent complete neuro-muscular recovery in a hypoventilating postop-erative patient. Conflicting findings regarding the neuromuscular effects of other acid–base changes may be due to coexisting alterations in extracellu-lar pH, intracellular pH, electrolyte concentrations, or structural differences between drugs (eg, mono-quaternary versus bisquaternary; steroidal versus isoquinolinium).

C. Electrolyte Abnormalities

Hypokalemia and hypocalcemia augment a non-depolarizing block. The responses of patients with hypercalcemia are unpredictable. Hypermagnese-mia, as may be seen in preeclamptic patients being managed with magnesium sulfate (or after intra-venous magnesium administered in the operating room), potentiates a nondepolarizing blockade by competing with calcium at the motor end-plate.

D. Age

Neonates have an increased sensitivity to nondepo-larizing relaxants because of their immature neu-romuscular junctions ( Table 11-8). This sensitivity does not necessarily decrease dosage requirements, as the neonate’s greater extracellular space provides a larger volume of distribution.


E. Drug Interactions

As noted earlier, many drugs augment nondepo-larizing blockade (see Table 11–4). They have mul-tiple sites of interaction: prejunctional structures, postjunctional cholinergic receptors, and muscle membranes.


F. Concurrent Disease

The presence of neurological or muscular disease can have profound effects on an individual’s response to muscle relaxants ( Table 11–9). Cirrhotic liver disease and chronic renal failure oftenresult in an increased volume of distribution and a lower plasma concentration for a given dose of


water-soluble drugs, such as muscle relaxants. On the other hand, drugs dependent on hepatic or renal excretion may demonstrate prolonged clearance (Table 11-8). Thus, depending on the drug chosen, a greater initial (loading) dose—but smaller mainte-nance doses—might be required in these diseases.

G. Muscle Groups

The onset and intensity of blockade vary among mus-cle groups. This may be due to differences in blood flow, distance from the central circulation, or differ-ent fiber types. Furthermore, the relative sensitivity of a muscle group may depend on the choice of mus-cle relaxant. In general, the diaphragm, jaw, larynx, and facial muscles (orbicularis oculi) respond to and recover from muscle relaxation sooner than the thumb. Although they are a fortuitous safety feature, persistent diaphragmatic contractions can be dis-concerting in the face of complete adductor pollicis paralysis. Glottic musculature is also quite resistant to blockade, as is often confirmed during laryngos-copy. The ED95 for laryngeal muscles is nearly two times that for the adductor pollicis muscle. Good intubating conditions are usually associated with visual loss of the orbicularis oculi twitch response.

Considering the multitude of factors influenc-ing the duration and magnitude of muscle relax-ation, it becomes clear that an individual’s response to neuromuscular blocking agents should be moni-tored. Wide variability in sensitivity to nondepolarizing muscle relaxants is often encountered in clinical practice.

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Clinical Anesthesiology: Clinical Pharmacology: Neuromuscular Blocking Agents : Nondepolarizing Muscle Relaxants: General Pharmacological Characteristics |


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