Muscle Relaxants in Infants and Children- How They Differ From Adults? Mohamed Naguib, MD
Department of Anesthesia
College of Medicine
University of Iowa
Muscle Relaxants in Infants and Children- How They Differ From Adults? Mohamed Naguib, MD
Department of Anesthesia
College of Medicine
University of Iowa
Structural and functional development of NMJ
Postnatal maturation of NMJ
Pharmacokinetic considerations
Succinylcholine in pediatric anesthesia
Nondepolarizing neuromuscular blocking drugs in pediatric anesthesia
Starts at 8 weeks of gestation
Myoblasts arise from the somite, motor axons from somata in the neural tube, and Schwann cells from the neural crest
All three cells travel to meet at the NMJ
Myoblasts fuse to form myotubes
Myotubes are approached by motor axons
Followed by Schwann cells
Initial contacts are unspecialized, yet capable of rudimentary transmission
After encountering the muscle surface the motor axon:
stops its growth
begins its characteristic differentiation into a presynaptic terminal
inducing formation of a motor endplate on the muscle surface
Formation of the NMJ depends on a series of reciprocal inductive interactions between the motor neuron and the muscle cell
Animals lacking either agrin or MuSK no NMJs:
Generally immobile
Unable to breathe
Die at birth
NMJ 1
2
3 Note stands of basal lamina stretching between
the nerve terminal and postsynaptic membranes -
rich in AChE Subsynaptic
nuclei express
a unique set
of genes 50 nm
EM Analysis of nAChR Synapse Cytoplasm 43K
Changes in AChR properties during development
a b, g, d Fast Denervated extrajunctional a, b, d, e Slow 2 weeks-adult a, b, g, d
Slow
birth a, b, g, d
Fast 16 days I.U. NMJ a, b, g, d
Fast < 14 days I.U. Pre-innervation Subunits Turnover Age
Structural and Functional Development
Type I fibers: slow, high oxidative “Marathon-fibers”
More sensitive to NDMRs
In the diaphragm, it constitutes:
14% in premature
26% in full-term neonates
55% in adults
The diaphragm is more active than the peripheral muscles during NM block in neonates
Structural and Functional Development
In neonates
NM transmission is immature until the age of 2 months
Response to tetanic stimulation and the rate of muscle contraction < older children
Greater individual variability to MRs
Body Composition During Growth
In neonates:
Total body water, ECF volume, and blood volume are relatively larger on a weight basis than they are in older patients
Muscle mass is smaller
MRs are distributed to a volume that mirrors ECF compartment
Body Composition During Growth
50 20 15 Muscle Mass (% body wt) 15 12 3 Fat (% body wt) 40 33 25 ICW (% body wt) 70 85-105 60 Blood Vol (ml/kg) 20 44 62 ECF (% body wt) 60 73 83 TBW (% body wt) Adult Full Term Premature
Some NDMRs and/or their metabolites are excreted in the urine, or in the bile
Neonatal hepatic enzyme systems are incompletely developed or absent
The ability to oxidize or reduce drugs is deficient in neonates, but increase to adult levels within a few days of life
Conjugative processes are severely limited at birth but mature by 3 months of age
The ability to hydrolyze substrates is as effective as in adults
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