Neuromuscular Block Guide

Need for Blockade
Monitoring
Dosing Principles
Drug Selection Principles
Drug Selection Specifics
Drug Pharmacology
Antagonism
Prices

Home-Amb-Card-Crit-Neuro-OB-Orth-Pain-Ped-Reg-Tran-Vasc-Misc

(based on Hugh Grant's page - see original for references, etc.)

Need for Neuromuscular Blockade

Not Needed: Integumentary, Breast
Intermittent: Intra-abdom, Intra-thoracic, Intracranial
Profound: Open Eyes

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Monitoring
1.    Monitoring of thumb is preferred

2.    Administration of MR should be based on clinical indications and guided by assessment of response to neuromuscular monitoring
3.    Train-of-four should be checked prior to administration of NDMR (to detect prolonged response to succinylcholine)
4.    Optimal relaxation (assuming adequate background anesthetic) = T1-T2 present in train-of-four count
5.    Knowledge of 6.    The deeper the block, the tougher it is to antagonize (see antagonism algorithm, chart #2) 7.    Detecting adequate reversal is difficult
% Receptors
Occupied
Response to
Nerve Stim
Signs
99-100 None Flaccid; rarely needed
95 PTF present Diaphragm moves; hiccough possible
90 TOF = 1/4 Abd relaxation adequate for most procedures
75 T1 = 100% baseline
TOF = 4/4
T4:T1 = 0.7
50-Hz tetanus sustained
TV, VC normal
50 100-Hz tetanus sustained Passes NIF test (?)
30 200-Hz tetanus sustained Head-lift, hand grip sustained
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Dosing:

  1. Need to know ED95, onset time, duration of relaxation (see pharmacology)
  2. Give ED95 x 1 initially (assuming patient already intubated using sux)
  3. Wait duration of onset time, check train-of-four count
  4. If train-of-four count > 2 at onset time dose ED95 x 1 again
  5. Titrate drug to therapeutic window (T1-T2 present only) during period of required relaxation
  6. Allow as much recovery as possible prior to antagonism of block
  7. Antagonize block with neostigmine 0.04-0.07 mg/kg + glycopyrrolate 0.01 mg/kg
  8. Use of volatile anesthetics reduce the requirement for neuromuscular blocking drugs in a dose-related fashion (1 MAC reduces ED95 by approx 1/3)
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Drug Selection Principles

There is a dynamic interaction between drug cost, weight of patient, and duration of relaxation needed. The table below demonstrates this interaction (it assumes intubation after 2x ED95 of the drug and standard top-up regimens given at the appearance of the third twitch in the train-of-four):
Prices are based on October 1999 UNC.
Drug Duration (70 kg) $ cost/ vial $ cost/ min
vec 90 min 7.84 0.09
atra 145 min 12.39 0.09
panc 140 min 1.26 0.01
miv  36 min 19.27 0.54
roc 43 min 11.22 0.26
cis 135 min 13.66 0.10
This is biased toward quantal use (e.g. opening a second vial of drug doubles the cost). The durations noted reflect complete use on one vial of drug. Alternative packaging and administration techniques can diminish waste of subsequent vials of drug while ensuring regard for sterility and prevention of disease transmission.

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Drug Selection Guidelines

  1. when duration of relaxation needed is longer than 1 hour
  2. when extubation is not planned immediately post-op
  3. when renal function is normal
  4. when patient < 70 years old
  5. when no comorbidity factors are present. This incorporates the data that suggests the immediate-acting (duration drugs) are more easy to reverse than pancuronium.
  1. presence of renal failure
  2. > 70 years old
  3. when complete reversal of NMB is absolutely essential at end of case (e.g. full stomach, morbid obesity, difficult airway, etc.)
  4. duration of case 35-60 minutes
  1. when complete reversal of NMB is absolutely essential at end of case (e.g. full stomach, morbid obesity, difficult airway, etc.)
  2. duration of case 35-60 minutes
  1. profound relaxation needed in case no longer than 35 minutes
  2. a succinylcholine drip, made by combining 5 (20mg/cc x 10cc) bottles is another valid alternative to mivacurium
  1. when succinylcholine is contraindicated
  2. when complete reversal of NMB is absolutely essential at end of case (e.g. full stomach, morbid obesity, difficult airway, etc.)
The following drugs have not been deemed to have clinical value our operating room: Back to Top of Page

Antagonism of Neuromuscular Blockade

  1. ALL NDMR's SHOULD BE PHARMACOLOGICALLY REVERSED BEFORE EXTUBATION (with possible exception of mivacurium)
  2. The most reliable signs of adequate restoration of neuromuscular function are CLINICAL signs: 5-sec head lift, 5-sec hand grasp, sustained masseter muscle strength, maximum NIF >= 50 cmH20 (i.e., more negative)
  3. No twitches present in the TOF Count represents an unantagonizable block
  4. Deeper blocks (e.g. T1 only present) are more difficult to antagonize than blocks where T2, T3 or T4 twitches are present in TOF Count
  5. To maximize muscle recovery, reversal ought not be given till TOF Count is at least 2.
  6. Longer-acting muscle relaxants (e.g. panc, curare, meto) are not as readily antagonized as intermediate or short duration muscle relaxants (e.g. vec, atra, roc, miv)
  7. Neostigmine is more effective in antagonizing deep blocks
  8. "No detectable fade" of DBS (Double Burst Stimulation) is the most reliable twitch monitoring sign of adequate restoration of neuromuscular function
  9. Combining knowledge of # of twitches in TOF Count present at time of reversal, the relaxant being antagonized and time since reversal can enhance the accuracy of detecting adequate restoration of neuromuscular function
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NDMR Pharmacology

Drug Potency* ED95
(mg/kg)
Duration
ED95 (min)
Cardiovascular Effects Elimination
Pancuronium 1 0.07 ~60 HR, ­BP 60% kidney 40% liver
Gallamine 0.025 2.8 ~60 HR, ­­BP 100% kidney
Curare 0.14 0.5 ~60 Histamine release ¯BP,
ganglionic blockade
40% kidney 60% liver
Metocurine 0.25 0.28 ~60 1/3 histamine of curare ¯BP,
ganglionic block 
60-90% kidney
Vecuronium 0.9 0.056 ~25 None 50% liver 20% kidney
Atracurium 0.25 0.26 ~25-30 1/3 histamine of curare ¯BP Nonspecific plasma esterases,
Hoffmann elimination
Mivacurium 0.875 0.08 ~19 similar to atracurium Hydrolysis: plasma cholinesterase
Doxacurium 2.3 0.03 ~60 minimal ¯BP ~50% kidney
Pipecuronium 1.4 0.05 ~60 None 75% kidney
Rocuronium 0.23 0.3 ~25-30 None, ? ­HR ~ 50% liver ~ 20% kidney
Cisatracurium 1.4 0.05 ~25-30 None Hoffmann elimination
*potency comparisons are to pancuronium 1 mg, ED95 is the estimated dose to produce 95% depression of twitch height. Duration ED95 is the time from injection until the T4/T1 ratio is 70% after a 1x ED95 dose.

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