Anesthetic Implications of Neuromuscular Disease
Edwards D. Briggs and Jeffrey R. Kirschy -USA
(J Anesth, 17:177–185, 2003)
Even in healthy patients neuromuscular blocking agents must be administered and monitored with great vigilance to ensure that adverse drug interactions do not occur and that residual postanesthetic muscle paralysis is prevented. The use of muscle relaxants in patients with neuromuscular disease presents several additional potential hazards. The current article addresses the anesthetic implications of some of the more common neuromuscular diseases, including multiple sclerosis, myasthenia gravis, muscular dystrophy, critical illness polyneuropathy, spinal cord injury, and Guillain-Barré syndrome. When caring for patients with these conditions, the anesthesiologist must perform a thorough preoperative assessment, select an appropriate anesthetic technique and muscle relaxant (if needed), and provide careful monitoring of both hemodynamic parameters and the extent of neuromuscular blockade.
(Survey of
Anesthesiology Volume 48, Number 4, August 2004)
Duchenne muscular dystrophy patients have a
high incidence of cardiac abnormalities and often eventually develop a dilated
cardiomyopathy that is frequently associated with mitral valve incompetence.
Dysrhythmias and cardiac conduction defects are common. Respiratory compromise
secondary to scoliosis is another major challenge complicating anesthetic
management. Cardiac arrest owing to succinylcholine-induced hyperkalemia has
been well documented. Muscular dystrophic patients are sensitive to
nondepolarizing neuromuscular blocking agents, but these drugs can be used
safely if their effects are properly monitored. Given the known association of
Duchenne muscular dystrophy with malignant hyperthermia, the use of triggering
agents should be avoided in patients with this condition.
Factors Influencing the Efficacy, Longevity, and Safety of Electroporation-Assisted Plasmid-Based Gene Transfer into Mouse Muscles
Maria J. Molnar, Rénald Gilbert, Yifan Lu,
An-Bang Liu, Athena Guo, Nancy Larochelle, Kristian Orlopp, Hanns
Lochmuller, Basil J. Petrof, Josephine Nalbantoglu, and George
Karpati - Canada
( Molecular Therapy, 2004 )
Intramuscular injection of plasmid is a
potential alternative to viral vectors for the transfer of therapeutic genes
into skeletal muscle fibers. The low efficiency of plasmid-based gene transfer
can be enhanced by electroporation (EP) coupled with the intramuscular
application of hyaluronidase. We have investigated several factors that can
influence the efficiency of plasmid-based gene transfer. These factors include
electrical parameters of EP, optimal use of hyaluronidase, age and strain of
the host, and plasmid size. Muscles of very young and mature normal, mdx, and
immunodeficient mice were injected with plasmids expressing B-galactosidase,
microdystrophin, full-length dystrophin, or full-length utrophin. Transfection
efficiency, muscle fiber damage, and duration of transgene expression were
analyzed. The best transfection level with the least collateral damage was
attained at 175–200 V/cm. Pretreatment with hyaluronidase markedly increased
transduction, which was also influenced by the plasmid size and the strain and
the age of the mice. Even in immunodeficient mice, there was a significant late
decline in transgene expression and plasmid DNA copies, although both still
remained relatively high after 1 year. Thus, properly optimized EP-assisted
plasmid-based gene transfer is a feasible, efficient, and safe method of gene
replacement therapy for dystrophin deficiency of muscle but readministration
may be necessary.