Neuromuscular Blockade in the ICU

Marcia Brackbill, Pharm.D., BCPS

Professor of Pharmacy
BJD School of Pharmacy
Shenandoah University
 Objectives
Explain the mechanism of action of neuromuscular
blocking agents used in the ICU/ED
Discuss the indications and clinical effects of
neuromuscular blockade
Identify concomitant medication(s) which are necessary
when a patient is on a neuromuscular blocker
Contrast the medications within each pharmacologic
class with regards to MOA, indication, pharmacokinetic
parameters (type of elimination), adverse effects and
precautions and/or contraindications
Identify appropriate therapeutic options to reverse
neuromuscular blockade
 Normal Neuromuscular
Transmission

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 Normal Neuromuscular
Transmission

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 MOA
Work on skeletal muscles postsynaptic nicotinic acetylcholine
(ACh) receptor
Two categories (same clinical result – Paralysis)
Depolarizing – works by binding to Ach receptors and causes
persistent depolarization of the neuromuscular endplate,
causing sustained contraction
Succinylcholine is structurally similar to acetylcholine (2 ACh
molecules bonded together)
Non-depolarizing – bind to alpha subunits of intra-junctional
ACh receptor on the postsynaptic membrane leading to
inhibition of current through receptor

What do you need to be sure the patient is receiving when

you administer a NMBA?
 Inhibited Transmission

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 NMBA’s
Depolarizing – Just one agent!
Succinylcholine (Anectin)
Very quick onset and short duration of action
Onset < 1 min
Duration: 5-10 min
Produces initial muscle fasciculation followed by a
flaccid paralysis
Frequently use for intubations
Not indicated for prolonged (i.e. continuous
infusion) use b/c of SE’s: release of histamine,
rising potassium levels, risk of malignant
hyperthermia, elevated intragastric and
elevated intraocular pressures
 NMBA’s
Non-Depolarizing
Chemical class: benzylisoquinoline
Atracurium (Tracrium)
Cisatracurium (Nimbex)
Chemical class: aminosteroid
Pancuronium (Pavulon)
Rocuronium (Zemuron)
Vecuronium (Norcuron)
 Indications for NMBA’s
Facilitate endotracheal intubation

Assist with mechanical ventilation (after sedation and

analgesia have been optimized)
ARDS (PaO2/FiO2 is < 150)

Immobilization for selected procedures

Increased intracranial pressures

Traumatic Brain Injury (TBI)

Prevention of shivering during implementation of cardiac

hypothermia protocols

Treat life threatening agitation refractory to aggressive

sedation and analgesic therapy
Contraindications of NMBA’s
Inability to obtain a secure airway
Patient not on analgesia and sedation
Unstable bone fractures
Relative contraindications include burns,
hemiplegia, hemiparesis, and peripheral
neuropathy
Receptors may be resistant to NMBAs and lead
to excessive doses
 Factors to Consider When
Selecting a NMBA
Duration of procedure - (duration of action)
Need for quick endotracheal intubation (onset of
action)
Adverse effect profile (hemodynamic instability,
histamine release)
PK/route of elimination (especially in patients with renal
or hepatic insufficiency)
Concurrent medications/drug interaction
Cost/Availability/Formulary Agents
 Comparison of NMBAs
Agent Onset of Action DOA Metab Comments
atracurium 2-4 min 30-40 Hoffman can be used in MOF;
causes MCD
cisatracurium 2-3 min 40-60 Hoffman can be used in MOF
pancuronium 4-6 min 120-180 renal causes MCD
vagolytic é HR , BP
rocuronium 1-2 min 30-40 hepatic facilitates intubation
é HR
vecuronium 2-4 min 30-40 hepatic no MCD/ histamine
release
MOF = multiple organ failure
MCD = mast cell degranulation and histamine release
 Factors Which May Prolong
the Action of NMBA Paralysis
Medications
Antibiotics (aminoglycosides, clindamycin, tetracycline,
polymyxin B, vancomycin), beta blockers, Ca channel
blockers, corticosteroids, local anesthetics, lidocaine

Clinical Conditions
Acidosis, renal/ hepatic failure, severe electrolyte toxicity
(i.e. hypermagnesemia), hypothermia, neuromuscular
disease (Myasthenia Gravis, Muscular Dystrophy), renal
failure
Factors Which May Prevent
Desired Levels of Paralysis
Medications
Anticholinesterase agents, carbamazepine
(Tegretol), phenytoin (Dilantin), ranitidine
(Zantac)
Clinical Conditions
Alkalosis, demyelinating lesions, diabetes,
peripheral neuropathies
 Reversal

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 Reversal Agents
MOA: acetylcholinesterase inhibitors
Prevent breakdown of acetylcholine in synaptic
cleft to overcome the NMBA
Neostigmine (Bloxiverz)
0.03mg/kg for rocuronium & shorter duration
agents
0.07mg/kg for vecuronium and pancuronium due to
longer duration of action
Edrophonium (Enlon) -less commonly used
10mg may repeat every 5-10min up to 40mg
 Reversal Agents (cont.)
MOA: Selective Relaxant Binding Agent (SRBA)
Selectively forms a tight complex with
aminosteroid NMBAs and removes them from the
NMJ into the plasma for removal
Sugammadex (Bridion)
Approved by the FDA December 2015
Potential advantage: provide more rapid reversal
of aminosteroid NMBAs
May allow for use of aminosteroids NMBA agents for
emergency intubations in patients where succinylcholine is
contraindicated

ADRs: Watch for bradycardia & hypersensitivity

reactions
Complications With NMBAs
Difficulty in clinical DVT
assessment of certain
pathologies Pressure ulcers
Acute abdomen, angina,
neurologic alterations
Corneal ulcers

Increased protein Prolonged paralysis may

catabolism be due to
1. accumulation of the
Tachyphylaxis drug
2. acute myopathy (AKA
Myositis ossificans acute quadraplegic
(calcification of the myopathy syndrome –
muscle) most serious side effect
and may occur with
Peripheral nerve damage infusions of 1-2 days)
Monitoring NMBAs

Critical: Always verify patient is receiving Image source:

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img%20banner/01x.jpg
sedation/analgesia !!
Train-of-Four (TOF)
Peripheral nerve stimulator –used to intermittently
monitor neuromuscular transmission during long-
term administration of muscle relaxants in the ICU
TOF – Electrode Placement
TOF – Procedure and Goals
Electrical stimuli (4) used to evoke a
"twitch" responses from the patient which may be
observed (tactile and visual observation) by the clinician
Goal - 1 twitch (out of 4 ) - which correlates to 90%
blockade
Decreases likelihood of prolonged paralysis/myopathy
When do you perform TOF monitoring?
Baseline
15 minutes after bolus dose (or change in infusion rate) titrate to
clinical endpoint every 15 minutes
When patient is clinical stable (at clinical endpoint), monitor
every 4 hours
Questions?