Page 467 - Clinical Application of Mechanical Ventilation

Pharmacotherapy for Mechanical Ventilation 433

coordinated muscular movement. Interruption at any point of the sequence causes
muscle relaxation or paralysis, depending on the effective dosage.
Neuromuscular blocking drugs are typically divided into two groups depending
on the modes of action at the neuromuscular junction.

Depolarizing Agents. The first group of neuromuscular blockers is classified as
depolarizing agents. This type of agent (e.g., succinylcholine) binds with the re-
depolarizing agents: Drugs
that prolong the depolarization ceptor site, producing quick onset and sustaining depolarization. Uncoordinated
phase of muscle contraction, thus muscle contraction called fasciculation marks the onset. Subsequent neuromuscu-
rendering the repolarization/
depolarization sequence (normal lar transmission is inhibited during the time that adequate concentration of suc-
mechanism for muscle movement) cinylcholine is bound to the receptor site (Ebadi, 1993).
impossible and causing muscle
blockade. An example is succinyl- There is no antidote for depolarizing agents. Succinylcholine is, however, rap-
choline (Anectine, Quelicin).
idly hydrolyzed by plasma pseudocholinesterase (PCHE). A small percentage of the
population has an abnormal plasma cholinesterase that does not hydrolyze succinyl-
choline within minutes, as expected. Plasma PCHE level may also be decreased in-
patients with insecticide poisoning, liver disorders (hepatitis, cirrhosis, obstructive
jaundice), malnutrition, acute infections, and anemias (Kee, 2005). These individu-
als may require ventilatory support for hours because of insufficient plasma PCHE.
Nondepolarizing Agents. The second group of neuromuscular blockers is classified as
nondepolarizing agents. These agents (e.g., Norcuron and Pavulon) compete with
nondepolarizing agents: Drugs
that compete with acetylcholine acetylcholine for the receptor sites at the motor endplates, thus blocking the normal
for the receptor sites at the motor action of acetylcholine. Since the nondepolarizing agents compete for the receptor
endplates, thus blocking the
normal action of acetylcholine sites, they are also called competitive agents. They are antagonized by anticholin-
and causing muscle blockade. esterase agents such as pyridostigmine and neostigmine. Anticholinesterase agents
Examples are vecuronium bromide
(Norcuron) and pancuronium allow ACh levels to rise and reverse the effects of nondepolarizing agents.
bromide (Pavulon).
Characteristics of Neuromuscular
Blocking Agents

Pharmacologically induced blockade progresses in the following sequence: rapidly
contracting muscles (eyes and digits) followed by larger and slower contracting mus-
cles (extremities, trunk, and diaphragm) (Halloran, 1991). Depolarizing agents (e.g.,
succinylcholine) have a quick onset but are short-lasting, making them the drugs of
choice for emergency intubation. Nondepolarizing agents have longer onsets rang-
ing from 3 to 10 min, but are longer lasting. These drugs are more appropriate for
controlled ventilation in the intensive care unit. Table 13-9 shows the characteristics
of selected depolarizing and nondepolarizing neuromuscular blocking agents.

Factors Affecting Neuromuscular Blockade

Several factors can alter neuromuscular transmission and blockade. They include
organ failure, drug interaction, electrolyte imbalance, and acid-base status.
Organ Failure. Patients with altered renal or hepatic function have an increased risk
of prolonged blockade. These patients can remain profoundly weak long after the
drug is discontinued. Both pancuronium bromide and vecuronium bromide have

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