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Muscle Relaxants in Children

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Muscle Relaxants in Children Chan Saysana, M.D. Indiana University Department of Anesthesia Section of Pediatric Anesthesia and Critical Care Neuromuscular Blockers ... – PowerPoint PPT presentation

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Title: Muscle Relaxants in Children


1
Muscle Relaxants in Children
  • Chan Saysana, M.D.
  • Indiana University
  • Department of Anesthesia
  • Section of Pediatric Anesthesia and Critical Care

2
Neuromuscular Blockers
  • Facilitate endotracheal intubation
  • Provide surgical relaxation
  • Facilitate controlled mechanical ventilation
    (both OR and ICU)
  • Decrease metabolic demand
  • Prevent shivering
  • Improve chest wall compliance

3
NMB in children
  • Growth and development NM junction
  • Age-related pharmacologic characteristics of NMB
    agents
  • Change in dose-response relationship
  • Duration of neuromuscular blockade

4
NMB in children
  • 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

5
Neuromuscular blockade in children
  • Immaturity of neuromuscular system
  • Ach receptor change in function and distribution
  • Lower values of TOF, post-tetanic facilitation,
    and marked fade during prolonged tetanic
    stimulation
  • 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
  • ED95 proportional to Vd/and concentration of
    blocker at effector site
  • Presence of greater number of fast muscles in
    ventilatory musculature
  • More liable for fatigue
  • Slow twitch fibers increase several fold in first
    6 mo
  • Closing volume w/i tidal volume
  • Airway closure occurs at end expiration
  • Aggravate hypoxemia/acidosis-potentiate relaxant

6
Neuromuscular blockade in children
  • Higher doses are required to block diaphragm vs.
    adductor pollicis
  • 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
  • Clinical signs antagonism different
  • Ability flex arm, lift leg, and return of
    abdominal muscle tone
  • Requirement neostigmine lower in children
  • With twitch response present, 20mcg/kg
    neostigmine and 5mcg/kg glycopyrrolate

7
Factors which affect Kinetic and dynamics of
relaxants
  • Major organ failure
  • Up regulation Ach receptors
  • Poor nutrition
  • Electrolyte/acid-base abnormalities
  • Hypothermia
  • Muscle atrophy

8
Neuromuscular Junction
  • 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 lt 2mo have lower TOF ratios as well as
    increased fade
  • Rate of Ach released during repeated nerve
    stimulation is limited in infants

9
Ach Receptor
  • Adult
  • epsilon subunit
  • Agonists depolarize less easily
  • Competitive agents block more easily
  • Fetal
  • gamma subunit
  • Agonists depolarize more easily
  • Competitive agents block less easily

10
(No Transcript)
11
Depolarizing Muscle Relaxant
  • Succinylcholine
  • Only depolarizing relaxant in use
  • Effective dose that cause 95 depression of
    twitch response (ED95) decreases with age
  • Infants have larger ECF volume
  • Birth- 45 (0.62mg/kg)
  • 2mo- 30 (0.73mg/kg)
  • 6yr- 20 (0.42mg/kg)
  • Adult- 16-18 (0.29mg/kg)

12
Succinylcholine
  • Repeated administration and continuous infusion
    results in tachyphylaxis
  • Phase II block (TOFlt50)
  • Effective when given intramuscularly
  • Short duration of action due to rapid hydrolysis
    by plasma cholinesterase (butyrylcholinesterase)
  • Synthesized by liver
  • Hydrolyzes several other compounds
  • Cocaine, chloroprocaine, remifentanil, esmolol,
    mivacurium

13
Succinylcholine Concerns
  • Decreased plasma cholinesterase activity
  • Little change in activity between 3mo and 12yr
    age
  • Plasma Cholinesterase deficiency
  • Heterozygous occurs 4
  • Homozygous 12000-3200

14
Succinylcholine Side Effects
  • Jaw stiffness
  • Increased masseter muscle tone
  • ? Association between increased masseter tone and
    trismus in pt with MH
  • Arrhythmias
  • Mild, transient increase HR
  • Bradycardia- vagal in origin, prior atropine
    decreases incidence
  • Hyperkalemia
  • 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
  • Increase in serum creatine kinase especially in
    patients with neuromuscular disease
  • Myoglobinemia to myoglobinuria
  • Increased Intraocular pressure
  • Mechanism unclear-?contracture of extraocular
    muscle vs. cycloplegic action of sch outflow
    resistance of aqueous humor
  • Malignant Hyperthermia

15
Succinylcholine
  • 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

16
Short-Acting Relaxant
  • Mivacurium
  • Benzylisoquinolinium
  • Potential for histamine release
  • Flushing, rarely hypotension
  • Rapidly hydrolyzed by plasma cholinesterase
  • Rare prolonged neuromuscular blockade in pt with
    plasma cholinesterase deficiency
  • heterozygous (15-20min duration)
  • homozygous (considerable)- reversal considered
    with evidence of muscle activity
  • 0.3mg/kg provides intubating condition in 1.3
    minutes

17
Intermediate-Acting Relaxants
  • Atracurium
  • Imidazole compound
  • ED95 0.1-0.17mg/kg
  • 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)

18
Atracurium
  • Plasma laudanosine concentrations tend to be
    higher in children with hepatic impairment
  • CNS effects
  • Side effects consist of flushing, anaphylactoid
    reactions or bronchospasm

19
Cisatracurium
  • One of ten stereoisomers of atracurium
  • 3x more potent than atracurium
  • 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

20
Vecuronium
  • 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 lt1yr age significantly more sensitive
    than older children
  • Infant larger VD lower plasma concentration
  • Residual weakness after discontinuation of
    long-term administration in patients with renal
    impairment

21
Rocuronium
  • 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 40-75min
  • Peak effect at laryngeal adductor occur faster
    than on the adductor pollicis

22
Rocuronium
  • Infants clear rocuronium slower than children
  • Infant larger VD
  • Renal failure clearance is decreased by 30 to 40
  • Increased duration of action in patient with
    hepatorenal disease

23
Long-Acting Relaxants
  • 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

24
Doxacurium
  • 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

25
Pipecuronium
  • Steroidal compound
  • Analog of pancuronium
  • No cardiovascular side effects
  • Duration similar pancuronium
  • ED95 80mcg/kg children, 60mcg/kg adult
  • Excreted by kidneys
  • Infants require less and recover more quickly

26
Summary
  • Physiologic considerations based on age, weight,
    and underlying illness
  • Pharmacodynamic differences
  • Pharmacokinetic differences
  • Onset time, duration, side effects
  • Hypotension, hypothermia, acidosis, hypoclacemia
  • Surgical procedure
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