programma - Nederlandse Vereniging voor Anesthesiologie

GASTSPREKER
Basic and Clinical Science in Neuromuscular Block
Lars I Eriksson, MD, PhD, FRCA
Professor and Academic Chair
Dept of Anesthesiology and Intensive Care Medicine,
Karolinska Institutet and Karolinska University Hospital,
Stockholm Sweden
Neuromuscular blocking agents (NMBAs) are widely used in anesthetic
practice and occasionally in patients within intensive care. The molecular
target for this class of agents are the nicotinic acetylcholine receptor
(nAChR), widely spread with the central and peripheral nervous systems. This family of
nicotinic cholinergic receptors consists of several subtype receptors, each having a typical
structural conformation and subsequent function within neuromuscular transmission
(muscle type nAChR) or neuronal control (neuronal subtype nAChRs). The nAChR is a
membrane-bound and ligand-gated ion channel that operate over a wide range of synapses
involved in critical control of vital functions.
Non-depolarizing NMBAs interact with all subtype nAChRs, hereby producing a classical
neuromuscular block with subsequent muscle paralysis and in addition an array of interactions
with regulatory control of vital functions with significant clinical relevance. The
interaction with muscle type nAChRs and neuronal subtypes nAChRs by non-depolarizing
NMBAs (but not depolarizing NMBA) give rise to impaired neuromuscular transmission
and typical changes in neurochemical transmission of action potentials over the synaptic
cleft. This lead to typical electrical (EMG) and mechanical response patterns underlying
the routine neuromuscular monitoring devices clinicians apply in daily clinical practice.
The relationship between NMBA dose and neuromuscular blocking effect (sensitivity)
varies considerably between different muscle groups, with muscles involved in pharyngeal
control and airway integrity being the most sensitive among the vital muscle
groups. In addition, the affinity of NMBAs to neuronal nAChRs lead to distinct changes in
neurotransmission within the wakefulness and regulation of breathing, and in particular
oxygen sensing and signaling systems involved in regulation of breathing during hypoxia.
Residual effects of NMBAs therefore target vital control of ventilation in such as way
that patient with residual neuromuscular block after extubation may encounter airway
obstruction, aspiration and impaired ventilatory response to acute hypoxia.
This lecture will provide basic molecular and cellular understanding of neuromuscular
transmission and other relevant areas of neurotransmission, and furthermore the
mechanisms by which neuromuscular blocking agents target regulatory control of vital
functions of clinical relevance for anesthesia and intensive care.