Transcript Muscle Relaxants in Children

Muscle Relaxants in
Children
Chan Saysana, M.D.
Indiana University
Department of Anesthesia
Section of Pediatric Anesthesia and Critical Care
Neuromuscular Blockers
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Facilitate endotracheal
intubation
Provide surgical relaxation
Facilitate controlled mechanical
ventilation (both OR and ICU)
Decrease metabolic demand
 Prevent shivering
 Improve chest wall compliance
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NMB in children
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Growth and development NM
junction
Age-related pharmacologic
characteristics of NMB agents
Change in dose-response
relationship
 Duration of neuromuscular
blockade
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NMB in children
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NM junction mature physically and
biochemically
Contractile properties of skeletal
muscle change
Amount of muscle in proportion to
body weight increases as age
Change in apparent Vd
Change in redistribution/ excretion
Change in rate metabolism
Neuromuscular blockade in
children
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Immaturity of neuromuscular system
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Longer elimination half-life of relaxants
General VD for most relaxants is about the same size as
the ECF volume (larger in infants than in older children or
adults)on weight basis
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ED95 proportional to Vd/and concentration of blocker at
effector site
Presence of greater number of fast muscles in ventilatory
musculature
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Ach receptor change in function and distribution
Lower values of TOF, post-tetanic facilitation, and marked
fade during prolonged tetanic stimulation
More liable for fatigue
Slow twitch fibers increase several fold in first 6 mo
Closing volume w/i tidal volume
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Airway closure occurs at end expiration
Aggravate hypoxemia/acidosis-potentiate relaxant
Neuromuscular blockade in
children
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Higher doses are required to block
diaphragm vs. adductor pollicis
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Clinical signs antagonism different
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If TOF of adductor is near normal, then can
assume diaphragm is fully recovered
Laryngeal adductors are less sensitive than
adductor pollicis to NDNMB, respose similar in
intensity and time course to orbicularis oculi
Ability flex arm, lift leg, and return of abdominal
muscle tone
Requirement neostigmine lower in children
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With twitch response present, 20mcg/kg
neostigmine and 5mcg/kg glycopyrrolate
Factors which affect Kinetic
and dynamics of relaxants
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Major organ failure
Up regulation Ach receptors
Poor nutrition
Electrolyte/acid-base
abnormalities
Hypothermia
Muscle atrophy
Neuromuscular Junction
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Incompletely developed at birth
Conduction velocity of motor nerves
increase throughout gestation as nerve
fibers are myelinated
Increase number of slow twitch fibers by 6
mo
Diaphragm and intercostal muscles
increase percentage of slow muscle fibers
in 1st month of life
Infants < 2mo have lower TOF ratios as
well as increased fade
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Rate of Ach released during repeated nerve
stimulation is limited in infants
Ach Receptor
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Adult
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epsilon subunit
Agonists depolarize less easily
Competitive agents block more easily
Fetal
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gamma subunit
Agonists depolarize more easily
Competitive agents block less easily
Depolarizing Muscle Relaxant
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Succinylcholine
Only depolarizing relaxant in use
 Effective dose that cause 95%
depression of twitch response
(ED95) decreases with age
 Infants have larger ECF volume
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Birth- 45% (0.62mg/kg)
 2mo- 30% (0.73mg/kg)
 6yr- 20% (0.42mg/kg)
 Adult- 16-18% (0.29mg/kg)
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Succinylcholine
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Repeated administration and
continuous infusion results in
tachyphylaxis
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Phase II block (TOF<50%)
Effective when given intramuscularly
Short duration of action due to rapid
hydrolysis by plasma cholinesterase
(butyrylcholinesterase)
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Synthesized by liver
Hydrolyzes several other compounds
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Cocaine, chloroprocaine, remifentanil,
esmolol, mivacurium
Succinylcholine Concerns
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Decreased plasma
cholinesterase activity
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Little change in activity between
3mo and 12yr age
Plasma Cholinesterase
deficiency
Heterozygous occurs ~4%
Homozygous 1:2000-3200
Succinylcholine Side Effects
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Jaw stiffness
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Arrhythmias
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Increase in serum creatine kinase especially in patients with
neuromuscular disease
Myoglobinemia to myoglobinuria
Increased Intraocular pressure
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Small change in normal children (clinically insignificant)
Life-threatening arrhythmia in burn injury, paraplegia, encephalitis, or
neuromuscular disease(Duchenne or Becker muscular dystrophy)
rhabdomyolysis
Myalgias
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Mild, transient increase HR
Bradycardia- vagal in origin, prior atropine decreases incidence
Hyperkalemia
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Increased masseter muscle tone
? Association between increased masseter tone and trismus in pt with
MH
Mechanism unclear-?contracture of extraocular muscle vs.
cycloplegic action of sch –outflow resistance of aqueous humor
Malignant Hyperthermia
Succinylcholine
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Routine use declined due to rare
life-threatening complications
with MH and cardiac arrest in
patients with undiagnosed
muscular dystrophy (1993)
Gold standard for most rapid
onset and brief duration of
action of all muscle relaxants
Short-Acting Relaxant
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Mivacurium
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Benzylisoquinolinium
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Potential for histamine release
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Rapidly hydrolyzed by plasma
cholinesterase
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Rare prolonged neuromuscular blockade in
pt with plasma cholinesterase deficiency
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Flushing, rarely hypotension
heterozygous (15-20min duration)
homozygous (considerable)- reversal
considered with evidence of muscle activity
0.3mg/kg provides intubating condition
in 1.3 minutes
Intermediate-Acting Relaxants
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Atracurium
Imidazole compound
 ED95 0.1-0.17mg/kg
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Intubating dose two to three times
provide intubating conditions w/i
2min- complete recovery w/i 40 to 60
min
Spontaneous decomposition
By nonspecific esterases
 Nonenzymatic hydrolysis (Hofmann
elimination)
 Inactive metabolites (laudanosine)
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Atracurium
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Plasma laudanosine
concentrations tend to be higher
in children with hepatic
impairment
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CNS effects
Side effects consist of flushing,
anaphylactoid reactions or
bronchospasm
Cisatracurium
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One of ten stereoisomers of
atracurium
3x more potent than atracurium
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Slower onset (lower dosage)
Hofmann degradation
Histamine release minimal even at
5X ED95
Lower plasma laudanosine level than
atracurium
Duration of action in renal failure
patients not significantly prolonged
Vecuronium
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Quaternary ammonium steroidal
compound
Absence adverse cardiovascular
effects even in high doses
Metabolized by the liver and
excreted in bile
Biphasic distribution of dose
requirement and duration of action
Infants <1yr age significantly more
sensitive than older children
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Infant larger VD – lower plasma
concentration
Residual weakness after discontinuation
of long-term administration in patients
with renal impairment
Rocuronium
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Mono quaternary steroidal compound
Low potency- therefore higher dose requirement
and faster onset
Primarily eliminated by the liver and the kidney
excretes ~10%
ED95 0.18-0.3mg/kg
0.6mg/kg produce 90-100% neuromuscular block in
0.8-1.3min
Mean recovery 25%- 28min, 90%-46min
Similar speed of onset in infants vs succinylcholine
 1.2mg/kg provided intubating conditions similar
to 1.5-2mg/kg succinylcholine w/I 30 sec.
 Time to recovery 25% twitch response ~4075min
Peak effect at laryngeal adductor occur faster than
on the adductor pollicis
Rocuronium
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Infants clear rocuronium slower
than children
Infant larger VD
Renal failure clearance is
decreased by 30 to 40%
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Increased duration of action in
patient with hepatorenal disease
Long-Acting Relaxants
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Pancuronium
Bisquaternary ammonium steroidal
compound
Induces tachycardia (increase CO)vagolytic
 Increase systolic blood pressure
 Advocated for various cardiac surgical
procedures
 Vagolytic properties blunt vagotonic
properties of narcotics
No histamine release
In neonate (NICU)
 Increase HR, BP, plasma Epi, NE levels
 ? Concern cerebral hemorrhage b/c
increased BP, increase CBF w/ less
autoregulation
Doxacurium
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Benzylisoquinolinium
ED95 30mcg/kg
Duration of action similar
pancuronium
No side effect at doses up to 3x ED95
Long term administration may lead to
residual weakness, decreased
coordination for several days to
weeks
Pipecuronium
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Steroidal compound
Analog of pancuronium
No cardiovascular side effects
 Duration similar pancuronium
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ED95 80mcg/kg children,
60mcg/kg adult
Excreted by kidneys
Infants require less and recover
more quickly
Summary
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Physiologic considerations
based on age, weight, and
underlying illness
Pharmacodynamic differences
Pharmacokinetic differences
Onset time, duration, side effects
 Hypotension, hypothermia,
acidosis, hypoclacemia
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Surgical procedure