Page 250 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

154 PART 2: General Management of the Patient

TABLE 22-4 Antipsychotic Agents
Haloperidol Quetiapine Olanzapine Risperidone Ziprasidone
Onset 2-5 minutes (IV) 1.5 hours 15-45 minutes 60 minutes <60 minutes
Elimination half-life 18 hours 6-12 hours 21-54 hours Up to 30 hours 2-7 hours
Metabolic pathway N-dealkylation CYP3A4 Hepatic CYP3A4 First-pass metabolism, hepatic, Hepatic, CYP2D6 Hepatic, glucuronidation via
glucuronidation with CYP450 CYP3A4 & CYP1A2
Active metabolite None N-desalkyl quetiapine None 9-hydroxy-risperidone None
Intermittent dosing 2-10 mg q6h 50 mg bid 10 mg qd 0.5 mg-3 mg bid 10-20 mg q4h
Sedation Moderate Moderate Low (dose dependent) Low Low
QTc prolongation risk High Moderate Low Low Moderate

instability. In addition to this, they are lipid soluble and thus accumulate Vecuronium: Vecuronium has also an aminosteroidal molecular struc-
in peripheral tissues after long-term infusions, leading to prolonged ture but a shorter half-life than pancuronium. After a bolus of 0.1 mg/kg,
recovery from sedation. These drugs may be used to induce a pharma- this drug typically lasts 30 minutes. Fifty percent of the drug is
cologic coma in patients with severe brain injury. excreted in bile, so prolongation of effect may be seen in patients with
Inhalational anesthetics such as isoflurane and sevoflurane have been liver dysfunction. In addition to this, one-third of the drug is excreted
studied in critically ill patients and shown to be safe and effective. in the kidneys, so accumulation in the setting of renal insufficiency
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These drugs have analgesic, amnestic, and hypnotic properties and may may be seen. The active metabolite 3-desacetylvecuronium may lead
be useful as single agents. Isoflurane undergoes only 0.2% metabolism, to prolongation of effect with repeated dosing, particularly in those
being eliminated almost exclusively through the lungs. Technical prob- with renal failure. Currently, it is very rarely used in the ICU.
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lems delivering the drug safely through the ventilator at accurate con-
centrations, as well as difficulty scavenging the exhaled gas, have limited Rocuronium: Rocuronium has also an aminosteroidal molecular
the widespread use of inhalational anesthetics for sedation in the ICU, structure. Unlike the other aminosteroidal nondepolarizing NMBs,
though research in this area is ongoing. rocuronium has a rapid onset of action. It may be used to facilitate
Table 22-4 summarizes pharmacologic properties of other commonly endotracheal intubation as a substitute for succinylcholine when
used sedative agents. the latter is contraindicated (eg, burns, muscle tissue injury, upper
motor neuron lesions). The usual bolus dose is 0.6 to 1.0 mg/kg, with
a duration of effect of 30 to 45 minutes, similar to vecuronium. The
NEUROMUSCULAR BLOCKING AGENTS metabolite, 17-desacetylrocuronium, has minimal neuromuscular
Neuromuscular blocking agents (NMBs) are used occasionally in blocking activity.
critically ill patients. The most common indication is for severe ARDS. Atracurium: Atracurium is a benzylisoquinolinium compound with a
A multicenter, double-blinded study evaluated the use of neuromuscular duration of action of between 20 and 45 minutes. The initial loading
blockade in early severe ARDS. The investigators reported an increased dose is 0.4 to 0.5 mg/kg. The drug is usually given by continuous infu-
90-day survival with no difference in ICU-acquired paresis. Other rare sion in the ICU at a dose of 10 to 20 μg/kg per minute. Atracurium is
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indications are to facilitate mechanical ventilation in patients with ven- inactivated in plasma by ester hydrolysis and Hofmann elimination,
tilator dyssynchrony despite optimal sedation, to manage tetanus with so renal or hepatic dysfunction does not have an impact on its dura-
chest wall rigidity, and to facilitate redistribution of blood flow away tion of blockade. This feature has made it attractive for use in ICU
from respiratory muscles in patients with acute hypoxemic respiratory patients because most patients sick enough to require NMBs suffer
failure accompanied by shock. It is mandatory that patients given NMBs from renal or hepatic dysfunction. Atracurium may cause histamine
be given agents to ensure amnesia while they are pharmacologically release, and its breakdown product, laudanosine, has been associ-
paralyzed. ated with central nervous system excitation and seizures in animal
Normally, at the neuromuscular junction, acetylcholine is released models. With the availability of cisatracurium, this drug is almost
from synaptic vesicles at the terminal end of the motor nerve. The never used in the ICU.
acetylcholine binds to the postsynaptic end plate, propagating an elec-
trical signal through the muscle and leading to muscle contraction. Cisatracurium: An isomer of atracurium is cisatracurium, which has
Pharmacologic NMBs bind to the acetylcholine receptor at the terminal a similar pharmacologic profile to atracurium. The initial loading
end of the motor nerve. These agents can activate the acetylcholine dose is 0.1 to 0.2 mg/kg, and the duration of action is approximately
receptor (depolarizing agents) or competitively inhibit the receptor 25 minutes. Like atracurium, this drug is inactivated in plasma by ester
without activating it (nondepolarizing agents). Succinylcholine is the hydrolysis and Hofmann elimination. Cisatracurium does not cause
only available depolarizing NMB. In normal individuals, depolarization histamine release. Because of its short half-life, it requires admin-
of skeletal muscle beds leads to release of intracellular potassium, typi- istration by continuous infusion. The usual dose is 2.5 to 3 μg/kg
cally resulting in an increase in the serum potassium level of approxi- per minute. This drug is used for virtually all neuromuscular blockade
mately 0.5 mEq/L. Denervation of skeletal muscle from tissue injury as in ICU patients.
in burns or upper motor neuron lesions may result in more dramatic ■
rises in serum potassium, which may precipitate cardiac dysrhythmias. MONITORING THE LEVEL OF NEUROMUSCULAR BLOCKADE
Succinylcholine may be used to facilitate endotracheal intubation but The depth of neuromuscular blockade is monitored most accurately
is not indicated for ongoing neuromuscular blockade in critically ill with use of a peripheral nerve stimulator. This device sends a current
patients and will not be discussed further in this chapter. between electrodes placed on the skin along the course of a peripheral
■ NONDEPOLARIZING NMBS nerve, most commonly the ulnar nerve. With this setup, the twitches
of the adductor pollicis muscle are evaluated to assess depth of neuro-
A number of nondepolarizing NMBs are available currently. The pharma- muscular blockade. The peripheral nerve stimulator is programmed to
cology of the ones more commonly used in the ICU will be discussed below. deliver four sequential stimuli at 2 Hz. Each stimulus causes release of

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