Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption, and Neuromuscular Blockade

The 2016 SCCM NMBA guidelines make no recommendation on the routine use of NMBAs for patients

undergoing therapeutic hypothermia after cardiac arrest (insufficient evidence). They recommend

use of a protocol that includes guidance on NMBA administration in patients undergoing therapeutic

hypothermia (good practice statement).

The optimal combination and dosing of sedatives and paralytics have not been well established

because the metabolism of these drugs is significantly slowed during hypothermia, and potency may be

decreased. NMBAs have been used in both a bolus and a continuous infusion fashion during therapeutic

hypothermia.

require administering analgesic and sedative drugs before and during neuromuscular blockade with the goal

of achieving deep sedation (good practice statement). They also suggest that patients receiving a continuous

infusion of NMBA should receive a structured regimen of physiotherapy (weak recommendation). It is

critical that patients be in a sedated, non-agitated, and pain-free state before initiating an NMBA. Once

the patient becomes paralyzed from the NMBA, the ability to accurately assess mental status or pain is

ostensibly challenging and often unattainable. The deeper the degree of paralysis, the higher the risk of

drug accumulation because nurses cannot routinely complete sedation interruption or taper to a lighter

level of sedation. Common scenarios that slow the clearance of sedatives (e.g., hepatic and renal failure or a

hypothermic state) can add to the likelihood of increased drug exposure and delayed awakening times once

the paralytic and sedatives are discontinued. This risk of drug accumulation underscores the importance of

a daily assessment for need of paralysis and frequent tapering of NMBA dosing once it is safe for the patient.

Two Classes of NMBAs According to Mechanism of Action: Depolarizing and Nondepolarizing:

Depolarizing NMBAs: Bind and activate acetylcholine receptors, causing persistent depolarization,

which then renders muscle fibers resistant to further cholinergic stimulation. Succinylcholine is the

only available depolarizing NMBA. Because of its quick onset and short duration, it is commonly used

for urgent or emergency intubation.

Pharmacokinetics: Hydrolyzed by plasma pseudocholinesterase

Usual dose: 0.05–1.5 mg/kg intravenously or intramuscularly

Onset intravenously: 30–60 seconds; intramuscularly: 2–3 minutes

Should not be used in patients with a history of malignant hyperthermia, hyperkalemia or risk

factors for hyperkalemia (stroke, paralysis, or spinal, crush, or burn injuries after 24 hours),

glaucoma, or penetrating eye injuries.

Adverse effects: Arrhythmias, bradycardia or tachycardia, hyperkalemia, rhabdomyolysis

acetylcholine at the neuromuscular junction. Divided into aminosteroid group (pancuronium,

vecuronium, and rocuronium) and benzyl isoquinolinium group (atracurium, cisatracurium,

doxacurium, and mivacurium).

Pancuronium: Long-acting aminosteroid; intermittent or scheduled bolus may be preferred to

continuous infusion because of accumulation and variable clearance. Older NMBA, not used much

in the United States.

Pharmacokinetics: Hepatically metabolized (30%–50%) and renally cleared as unchanged

drug (50%–70%). Accumulation and prolonged duration of paralysis will occur with varying

degrees of hepatic and/or renal dysfunction. Duration about 60–120 minutes.

ii.

Adverse effects: Vagolytic activity, sympathetic stimulation, bradycardia, prolonged effect