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

initially before continuous infusion, particularly if organ dysfunction is present. The duration of paralysis

for NMBAs cleared by Hofmann degradation may be more reliable when used as a continuous infusion

because their clearance is not dependent on renal or hepatic function.

Train-of-Four (TOF) Monitoring and Dose Titration

The SCCM NMBA guidelines make no recommendation concerning the use of electroencephalogram-

derived parameters (e.g., Bispectral Index [BIS], E-entropy, Cerebral State Index, and Patient State

Index) as a measure of sedation during continuous NMBA administration (insufficient evidence).

They suggest against the use of peripheral nerve stimulation (PNS) with TOF alone for monitoring the

depth of neuromuscular blockade in patients receiving continuous NMBA infusions (very low quality

evidence). They make no recommendation on the use of PNS to monitor the degree of block in patients

undergoing therapeutic hypothermia (insufficient evidence). Typically, the goal of using an NMBA is

to improve patient-ventilator synchrony and increase oxygenation. This may be achieved with varying

degrees of paralysis and may not necessitate 100% block.

with measured oxygenation parameters, helps find the “lowest effective paralytic dose” and allows

quicker recovery of spontaneous neuromuscular transmission once the NMBA is discontinued. Some

clinicians do not believe that TOF monitoring is necessary and believe that using the clinical values

alone is sufficient to determine NMBA dosing.

TOF delivers four supramaximal electrical impulses every 0.5 seconds to the ulnar, facial, or posterior

tibial nerve. Response to the impulse is then measured by muscle twitches visualized from the associated

innervated muscles (thumb or eye). Goals of paralysis can usually be reached with 2 or 3 of 4 twitches;

0 of 4 twitches indicates complete neuromuscular blockade, usually necessitating a decrease in NMBA

dose. Oxygenation goals may be reached even with 4 of 4 twitches, indicating that the NMBA dose is

effective and an increase is not warranted.

A baseline electrical current should be established before initiating an NMBA to determine how

much electrical current is needed to produce a twitch. Usually 10–20 mA (amperage) is sufficient. The

conduction of the electrical impulse may be dampened because of peripheral edema, loss of electrode

adhesion, incorrect electrode placement, and hypothermia, which can lead to inaccurate readings.

These factors should be reassessed with each use of the TOF.

Complications of NMBAs

Prolonged weakness: Several case reports associate the use of NMBAs and prolonged weakness,

which could include myopathy, polyneuropathy, or neuromyopathy. Other risk factors may include

concomitant use of corticosteroids, persistent hyperglycemia, and type of NMBA used. However,

data are inconsistent and not controlled, and further studies are needed to clarify specific risk factors

for prolonged weakness associated with NMBAs. Following a trend in creatine kinase concentration

every 48–72 hours may help assess the presence of myopathy secondary to paralysis and prolonged

immobilization. A creatine kinase concentration should not be solely relied on for the presence of

myopathy, and daily determination of the need for the NMBA should still be considered, even with a

normal creatine kinase.

corneal ulcerations and infection. Prophylactic eye protection must be used in all patients on NMBAs

(e.g., lubricating eye ointments or eye covers).

Thrombosis: Caused partly by immobility, patients receiving an NMBA may be up to 8 times more

likely to have a DVT than those not on an NMBA. Prophylaxis for a DVT must be provided for all

patients on an NMBA.