University of Maryland Medical Center

ICU NEUROMUSCULAR BLOCKADE

Guidelines for Use

Neuromuscular blocking agents (NMBAs) may facilitate various medical

interventions, to include mechanical ventilation. NMBAs should be used only after all
other measures/therapies are attempted (ie, sedation, new ventilator technologies). The
following guidelines were designed for the long-term use of NMBAs ( ≥ 24 hours) in the
ICU. These guidelines are not intended for patients receiving NMBAs for short-term or
occasional use.
NMBAs provide no analgesia or sedation. All patients receiving NMBAs must
receive a concurrent, around-the-clock benzodiazepine to provide sedation and amnesia.
Pediatric patients receiving NMBAs must concurrently receive a benzodiazepine or
chloral hydrate for sedation. Concurrent opiate administration will be indicated for those
patients with pain (post-op, trauma, etc.), but is not a substitute for an amnestic sedative
agent.
Appropriate sedation/analgesia should be evaluated by assessment of changes in
parameters that may indicate stress or pain. Unexplained elevations in heart rate or blood
pressure, diaphoresis, or tearing may indicate anxiety or wakefulness in the patient
receiving NMBAs. Drugs such as beta blockers should not be employed to control
undefined tachycardia in patients receiving NMBAs.

A. INDICATIONS:

Neuromuscular blocking agents to produce muscle paralysis in the ICU are

indicated, but not limited to the following situations:
1) difficult mechanical ventilation (ie, hypoxia with maximal ventilatory support, high
airway pressures)
2) elevated intracranial pressure
3) post-operative “open chest”
4) procedures requiring no movement of the patient such as tracheal intubation,
bronchoscopy, etc.
5) extraordinary life support modalities such as ECMO, ECLA, LVAD, RVAD, or
IABP
6) acute pulmonary hypertension in pediatric patients
7) high frequency, oscillatory ventilation

B. DEFINITIONS:

For the purpose of these guidelines, short-term and long-term paralysis shall be
defined as:
1. Short-term paralysis < 24 hours
2. Long-term paralysis ≥ 24 hours
C. AGENTS OF CHOICE FOR PROLONGED (≥ 24 hours) ICU PARALYSIS:

For most adult and pediatric patients, the neuromuscular blocking agents of choice
are pancuronium or doxacurium. The preferred method of administration for pancuronium
and doxacurium is scheduled bolus dosing. However, both agents may be administered
by continuous infusion. Bolus doses should be administered by slow IV push to minimize
any histamine-related side effects.
Atracurium and cisatracurium use should be restricted to patients with renal and
hepatic failure. Atracurium will be considered therapeutically equivalent to cisatracurium
for long-term ICU paralysis. Atracurium and cisatracurium should be administered by
continuous infusion.
NMBA orders should be written to titrate the agent to a certain number of twitches
on train-of-four (TOF) monitoring (ie, titrate to 1-2 twitches out of four on TOF).

1) Pancuronium:

ADULTS=> Loading dose: 0.05-0.1 mg/kg

Maintenance: i) 0.02-0.05 mg/kg IV q2hr
(2mg IV q2hr- usual initial dose)
or
ii) 0.02-0.03 mg/kg/hr infusion
if dosing interval becomes
shorter than every 2 hours
(usual initial rate- 1-2mg/hr).
NOTE: Extended intervals (ie, q 3hr) or decreased infusion rates may be
necessary for patients with significant renal or hepatic insufficiency.

PEDIATRICS=> Load/bolus: 0.1-0.15mg/kg/dose q 1-2 hours

Infusion: 0.1mg/kg/hr
NOTE: May cause tachycardia, increase in SBP and cardiac output.

2) Doxacurium:

ADULTS=> Loading Dose: 0.04 mg/kg

Maintenance: initial- 0.025 mg/kg IV q 2 hr
( 2mg IV q 2hr- usual initial dose)
NOTE: Renal dysfunction- extend dosing interval (ie, q3-4hr).
Infusion generally not needed, but is available.

PEDIATRICS=> Load: 0.03-0.1mg/kg

Maintenance: 0.03-0.15mg/kg/dose q 2-4 hours
NOTE: Doxacurium contains benzyl alcohol. Use with caution in infants.
D. SECOND-LINE AGENTS:

Atracurium and cisatracurium should be limited to patients with multiorgan

dysfunction (renal and hepatic) when the other NMBAs are unacceptable.
Atracurium will be considered therapeutically equivalent to cisatracurium for long-
term ICU paralysis. The preferred agents (pancuronium and doxacurium) may be
used in multiorgan failure with appropriate train-of-four monitoring and close
titration of dose.

1. Atracurium:

ADULTS & PEDIATRICS= Load: 0.4-0.5 mg/kg

Maintenance: 2-15 mcg/kg/min continuous infusion
(usual dose 7-8 mcg/kg/min)

2. Cisatracurium:

ADULTS & PEDIATRICS= Load: 0.1mg/kg

Maintenance: 0.5-10 mcg/kg/min infusion
(usual dose 3mcg/kg/min)

E. MONITORING DURING NEUROMUSCULAR BLOCKADE

i) Methods of monitoring degree of paralysis:

1) peripheral nerve stimulator (train-of-four)- Train-of-four (TOF)/ peripheral

nerve stimulation is the standard of care to monitor level of neuromuscular
blockade. Appropriate paralysis using TOF monitoring is generally considered 85-
90% blockade as indicated by 1-2 twitches out of four via the TOF monitoring. The
consistent use of TOF will minimize drug accumulation, but may not prevent
prolonged paralysis/prolonged weakness seen in some patients after
discontinuation of NMBAs. The physician should write the NMBA orders specifying
the number of twitches desired (ie, Doxacurium 2-3mg IV q2-3hr, titrate to 1-2
twitches out of 4 on TOF).

2) compliance with ventilatory support- Appropriate neuromuscular blockade

is indicated clinically by the patient accepting ventilation without overbreathing or
dysynchrony, and with reduced airway pressures, absent gag/cough reflex during
tracheal suctioning, and no visible extremity movements.

ii) Procedures for monitoring patient during prolonged paralysis (≥24 hours):
1. All patients receiving around-the-clock neuromuscular blockade should be
monitored with a peripheral nerve stimulator in addition to the clinical assessment
of ventilator compliance.

2. Train-of-four must be assessed at least every 12 hours, and 4 hours after each
 dosage change.

3. Results of train-of-four monitoring will be recorded on the nursing flowsheet

along with any dose adjustments.

4. Train-of-Four Procedures:
a) TOF may be performed at the ulnar or facial nerve. Ulnar nerve stimulation may
become difficult if there is significant peripheral edema. Facial nerve
stimulation may be more appropriate in this situation. In addition, the facial
nerve may correlate better with paralysis of the diaphragm.

b) Place 2 standard EKG electrodes along the ulnar nerve approximately 2-3
inches apart.

c) Attach alligator clips to the electrodes (polarity unimportant).

d) Explain to the patient what you are going to do (ie, “checking your muscle
response”, “you’ll feel 4 tingles in your arm”, etc.).

e) Prior to initiation of NMBA, when possible, a baseline TOF should be performed

to determine the minimum stimulus (mAmps needed to produced 4 strong
twitches).
1. Set the peripheral nerve stimulator to 20-30 mAmps and depress TOF
pad on the stimulator.
2.Watch for twitches or feel for twitches in the thumb or hand.
3. Increase the mAmps until 4 strong twitches are seen/felt.

f) Once NMBA is started, check TOF in same location and start with the same
current (mAmps) that produced twitches the last time TOF was checked. Increase
the current until twitches are seen or until maximum on nerve stimulator.

g) If no twitches are seen/felt, perform troubleshooting procedures (ie, reverse

alligator clips, check electrode placement, check batteries). If no technical
problems are discovered, hold NMBA until 1-2 twitches return, then restart at a
decreased dose.

h) A goal level of paralysis for most ICU patients is 1-2 twitches. See TOF chart for
interpretation of twitches and example dose adjustments.
TRAIN-OF-FOUR

# of Degree of Paralysis Suggested Dose Adjustments

Twitches
0 100%- complete blockade
Drug accumulation or electrical
current during nerve stimulation
not transmitted.
1 90% blockade
Hold dose until 1 out of 4 twitches returns on
TOF and restart at a decreased rate or
extend the interval. (ie, 10% less on infusion
rate or extend interval from q2hr to q3-4hr)
Continue current dose.

Goal for paralysis of diaphragm.

2 ≈ 85% blockade
Acceptable goal for most
patients.
3 ≈ 80% blockade
Acceptable for some patients.
4 < 75% blockade
Residual blockade may be
present.
Continue current dose or rebolus and
increase maintenance dose if 1:4 twitches is
desired. (ie, increase rate/dose by 10%)
Continue current dose or rebolus and
increase maintenance dose for more
paralysis (ie, increase by 10%).
Rebolus, and increase rate/dose (ie,
increase by 10-20%). If patient is recovering
from the NMBA, may use a 5 second head-
lift to check for residual paralysis.

5. Drug holidays (discontinuation of the infusion or holding of a scheduled dose

for several hours) should be considered after 5 days of continuous administration,
or after 48 hours if the patient is receiving concurrent steroids. The purpose
of the drug holiday is: 1) to assess if the indication for the NMBA still exists; and 2)
to assess the time necessary for the patient to recover from the neuromuscular
blockade. In general, if it takes a time equal to or greater than 4 half-lives of the
NMBA to recover 3-4 twitches after the NMBA is held, then the dose and/or
interval should be adjusted prior to restarting the NMBA. If the indication for
neuromuscular blockade no longer exists after withdrawal, the NMBA should be
discontinued.

Example drug holiday procedure:

1. Consider a drug holiday for stable patients.

2. Hold NMBA if patient has received ≥ 5 days of NMBA therapy without other
interacting medications or if patient has received ≥ 2 days of therapy with
concurrent steroids.
3. Start checking TOF beginning 1 hour after the end of the last dosing interval or 1
hour after stopping an infusion. Check TOF every hour until 3-4 twitches are
recovered.
Pancuronium or Doxacurium
-If interval is q 2 hr, start checking TOF 3 hours after
last dose.
-Check TOF q 1 hr, until 3-4 twitches.
-If time to recover 3-4 twitches is ≥ 6-8 hours, and the
patient still requires paralysis (ie, desaturates or ICP
increases), then restart at an extended dosing
interval (ie, q3-4 hr) or 10% decrease in the infusion
rate.
Atracurium or Cisatracurium
-Start checking TOF 1 hour after
infusion is stopped.
-Check TOF q 1 hr, until 3-4
twitches.
-If time to recover 3-4 twitches ≥2
hours, and patient still requires
paralysis, then restart at 10% less.

F. ADVERSE EFFECTS:

1. Histamine release: generally, insignificant clinically but may occur with all the
NMBAs in large bolus doses, administered rapidly.

2. Cardiovascular: tachycardia (vagolytic), bradycardia, mild hypotension (least

common with doxacurium and cisatracurium)

NOTE: The tachycardia associated with pancuronium is usually not clinically

significant in adults, with an average increase of 10 beats/minute.

3. Tachyphylaxis: therapeutic resistance may occur with all NMBAs due to up

regulation of the receptors; may occur less with bolus dosing

4. Prolonged neuromuscular blockade from accumulation: minimized with regular

TOF monitoring

5. Post-paralytic syndrome: occurs with all agents, unpredictable. All of the

common NMBAs (vecuronium, pancuronium, atracurium, doxacurium) have been
implicated with post-paralytic syndrome/prolonged weakness. This weakness is
caused by denervation of muscle and/or a result of NMBA interaction with various
medications. Patients at high risk for prolonged weakness, in whom use of NMBAs
should be avoided, include those receiving concurrent corticosteroids,
aminoglycosides, and/or immunosuppressives. The occurence of prolonged
paralysis is unpredictable and may take weeks-months to reverse. The severity of
this syndrome can range from mild weakness to quadraplegia. The use of
corticosteroids appears to be a risk factor for development of postparalytic
syndrome/prolonged weakness regardless of the chemical structure of the NMBA
(even nonsteroidal NMBAs).

6. Other concerns:
-Skin breakdown (frequent turning needed)
-Corneal drying (scheduled lacrilube to prevent)
-Deep vein thrombosis (consider compression device or SQ heparin)
-Inadequate sedation and analgesia (monitor for increases in HR,BP,
 diaphoresis, and tearing during times of potential stress- see attached
UMMS sedation score for more information)
-Aspiration risk (elevate head of bed if enteral feedings are used)
-Secretion removal

G. DESIRED OUTCOMES:

1) Achieve optimal ventilation without adverse effects.

2) Achieve appropriate paralysis while minimizing NMB dose.
3) Prevent delays in ventilator weaning due to prolonged paralysis.
4) Provide cost-effective therapy.

Bibliography:
1. Shapiro BA, et al. Practice parameters for sustained neuromuscular blockade in the
adult critically ill patient: an executive summary (SCCM guidelines). Crit Care Med
1995;23:1601-1605.
2. Davidson JE. Neuromuscular blockade: indications, peripheral nerve stimulation, and
other concurrent interventions. New Horizons 1994;2:75-84.
3. Watling SM, Dasta JF. Prolonged paralysis in intensive care unit patients after the use
of neuromuscular blocking agents: a review of the literature. Crit Care med 1994;22:884-
93.