ANESTHETICS RESEARCH

JOURNAL ARTICLES

Anesthesia for Charcot-Marie-Tooth disease: a review of 86 cases
by Joseph F. Antognini M.D.

ABSTRACT: Operative charts were reviewed in 86 patients with Charcot-Marie-Tooth disease, a condition characterized by chronic muscular denervation. A total of 161 surgical procedures was performed. Major complications were few, and one operative death occurred, unrelated to anesthesia. Succinylcholine and malignant hyperthermia triggering agents were used in 41 (48%) and 77 (90%) patients, respectively, without untoward effects. Contrary to previous reports, this survey supports the safe use of succinylcholine and MH triggering agents in this disease.
Key words
ANESTHESIA:
MUSCLE: denervation:
SYNDROMES: Charcot-Marie-Tooth disease.

From the Department of Anesthesiology, University of California, Davis Medical Center, Sacramento, Calif.
Accepted for publication 27th December, 1991.

Charcot-Marie-Tooth disease (CMTD), also known as hereditary motor and sensory neuropathy, is a rare neurological condition that affects peripheral nerves, primarily of the distal musculature.1.2 Denervation with subsequent muscular atrophy is the hallmark of this disease. There are only five reports of anesthesia in patients with CMTD. 3-7 with some raising the possibility of succinylcholine-(SCH)induced hyperkalaemia and one4 suggesting that these patients may be susceptible to malignant hyperthermia (MH). This report summarizes the anesthetic management of 86 patients with CMTD, many of whom received SCH and MH triggering agents safely.
Methods
Questionnaires and medical release forms were sent to approximately 1,000 members of Charcot-Marie-Tooth International, an organization dedicated to helping patients with CMTD. Questions included age, anesthetic/surgical history, dates of diagnosis and onset of symptoms, severity of disease and history of familial problems with anesthesia and surgery. Most patients could not remember the disease severity adequately at the time of each procedure, so current severity is reported.
Medical records (anesthetic record, discharge summary, history and physical, recovery room record and preoperative anesthetic evaluation) were obtained and information regarding surgery, type of anesthesia and complications was extracted. Complete records could not be obtained on all of the respondents; however, no patient was included if an anesthetic record was unavailable or if the surgical procedure preceded the onset of symptoms.
Results
One hundred ninety-three questionnaires were returned. For several reasons (foreign hospital, surgery in remote past, incomplete records, etc.), medical records were obtained on only 86 of these patients, with 161 surgical procedures performed. For each procedure the age was 41 = 17 yr (mean = SD), range 2-75 yr; duration of symptoms was 23 = 14 yr, range 0-59 yr. Sixty-nine of 86 patients (80%) had symptoms in all extremities.
The majority (53%) of the procedures were orthopedic. Other surgery included peripheral (17%), intra-abdominal (7%), obstetrical/gynecological (7%), and miscellaneous (17%). General anesthesia was used for 139 procedures in 78 patients, while regional and local anesthesia were used for 22 procedures in 18 patients. Malignant hyperthermia triggering agents (succinylcholine and/or potent inhalational anesthetics) were given to 77 (90%) patients for 130 procedures.
Succinylcholine was used during 56 operations in 41 (48%) patients. Pre-treatment with a "defasciculating" muscle relaxant was used in 32 of these 56 exposures. A paralyzing dose of a nondepolarizing agent was used during 50 episodes in 39 (45%) patients: of these, 26 (30%) had pharmacological reversal.
Complications included 19 (22%) patients who complained of "weakness" postoperatively, one unexpected admission to the intensive care unit secondary to postoperative hypotension, and two patients who developed pneumonia, one of whom died. There were no other deaths reported by family members. No complications occurred as a result of muscle relaxants, i.e., objective weakness, prolonged intubation or reintubation.
Discussion
Anesthesia in these CMTD patients appeared to be tolerated well with few complications. The only perioperative death was in a young girl who had severe restrictive lung disease and developed pneumonia subsequent to spinal fusion. Other complications were relatively minor. However, this survey is necessarily biased because information was obtained from patients who were able to respond, or from their parents. Since CMTD tends to be familial, this bias was minimized by requesting information regarding any family members who had had problems with surgery and anesthesia. Nonetheless, complications and deaths may have been under-reported. Also, this survey was retrospective, with sometimes incomplete data obtained from differing institutions. Such a data source could have obscured important trends in perioperative morbidity and mortality in CMTD.
Patients with CMTD have chronic denervation, often of all extremities. Since denervation is one of the most potent predisposing factors for release of potassium after exposure to SCH8.9 previous reports have cautioned against its use in CMTD. This survey indicates that SCH is well tolerated. While a small "defasciculating" dose of a non-depolarizing muscle relaxant may lessen the potassium release from diseased muscle,8 patients who had SCH alone had no apparent problems.
The massive release of potassium resulting from SCH is not an all-or-none phenomenon. A group of patients susceptible to this complication develop varying degrees of hyperkalaemia;10 some may manifest subtle ECG changes, some may develop peaked T waves, while others can have malignant arrhythmias and cardiovascular collapse. If CMTD patients were sensitive to the hyperkalaemic effect of SCH, some ECG and haemodynamic changed should have been found. Their absence indicates that SCH is probably safe in CMTD. However, because the plasma potassium concentration was not measured in these patients, the true risk is unknown. In addition, any acute exacerbation in CMTD may alter the amount of involved muscle and therefore change the sensitivity to SCH.
The range of age and symptom duration was wide, indicating that the degrees of chronicity was not an important influence on outcome. Also, symptom severity was not a factor. Nearly 80% of all patients had involvement of all extremities. Thus, regardless of whether a patient has had recent onset of symptoms or has had long-standing disease, SCH is well tolerated. Presumably, the process of denervation is much slower than the atrophic process, such that the amount of muscle which can release potassium is relatively small.
Very few patients developed pulmonary complications, i.e., pneumonia. In the past, pulmonary involvement in CMTD was thought to be uncommon. However, more recent data suggest that respiratory muscles may be affected, with a restrictive lung pattern predominating.11.12 The patient of the report by Brian et al,3 was ventilator-dependent for approximately one month following a Caesarean section. Involvement of the phrenic nerve13 and the nerves subserving expiratory muscles14 may have been responsible. Patients may have few or no symptoms despite considerable abnormalities in pulmonary function. The presence of proximal muscle weakness of the arms may be a predictor for respiratory muscle weakness.11
Theoretically, muscle weakness related to loss of motor units might sensitize a patient to nondepolarizing muscle relaxants. In this survey, however, no patient appeared to have any complications vis-a-vis muscle relaxants, i.e., prolonged block. This possible complication was probably adequately evaluated, as the nerves which are used clinically to monitor neuromuscular function may be affected by CMTD, including the posterior tibial, ulnar and facial nerves.
One report has raised the issue of MH.4 While several neuromuscular diseases are associated with MH, based on our understanding of the pathophysiology of CMTD and MH, there is no reason to suspect that a connection between the two exists. Most patients received MH triggering agents without untoward effects. However, the relatively small sample size of this survey does not exclude a potential link.
The CMTD patients evaluated in this survey appeared to tolerate anesthesia well. Although SCH has been considered to be contraindicated in this disease, no complications occurred from its use in these patients who had chronic symptoms. An acute exacerbation, however, might render SCH use inadvisable. Other risks, including sensitivity to neuromuscular blocking agents and MH, are probably minimal. The possibility of occult pulmonary dysfunction should be considered, but, in general, the anesthetic management in CMTD can be adjusted to the needs of the individual patient.
References
1. Harding AE, Thomas PK. The clinical features of hereditary motor and sensory neuropathy Types I and II. Brain 1980; 103: 259-80
2. Adams RD, Victor M. Principles of Neurology. 3rd ed. New York: McGraw-Hill 1985; 987-8.
3. Brian, JE, Boyles GD, Quirk JG, Clark RB. Anesthetic management for Cesarean section of a patient with Charcot-Marie-Tooth Disease. Anesthesiology 1987; 66: 410-2.
4. Roelofse JA, Shipton EA. Anaesthesia for abdominal hysterectomy in Charcot-Marie-Tooth disease. A case report. S Afr Med J 1985; 67: 605-6.
5. Hirota K, Muraoka M, Sugihara K, Amano N, Matsuki A, Oyama T. Anesthetic experience of a patient with Charcot-Marie-Tooth disease. Masui 1988; 37: 207-10.
6. Sugai K, Sugai Y. Epidural anesthesia for a patient with Charcot-Marie-Tooth disease, bronchial asthma and hypothyroidism. Masui 1989; 38: 688-91.
7. Watanabe T, Yamashita M, Kondo Y, et al. Anesthetic and post-operative management of Charcot-Marie-Tooth disease. Masui 1982; 31: 530-4.
8. Gronert GA, Lambert EH, Theye RA. The response of denervated skeletal muscle to succinylcholine. Anesthesiology 1973; 39: 13-22.
9. Gronert GA, Theye RA. Pathophysiology of hyperkalemia induced by succinylcholoine. Anesthesiology 1975; 43: 89-99.
10. Cooperman LH. Succinylcholine-induced hyperkalemia in neuromuscular disease. JAMA 1970; 213: 1867-71.
11. Nathanson BN, Yu DG, Chan CK. Respiratory muscle weakness in Charcot-Marie-Tooth disease. A field study. Arch Intern Med 1989; 149: 1389-91.
12. Laroche CM, Carrol N, Moxham J, Stanley NN, Evans RJC, Green M. Diaphragm weakness in Charcot-Marie-Tooth disease. Thorax 1988; 43: 478-9.13.
13. Gilcrist D, Chan CK, Deck JHN. Phrenic involvement in Charcot-Marie-Tooth disease. A pathologic documentation. Chest 1989; 96: 1197-9.
14. Eichacker PQ, Spiro A, Sherman M, Lazar E, Reichel J, Dodick F. Respiratory muscle dysfunction in hereditary motor sensory neuropathy, Type I. Arch Intern Med 1988; 148: 1739-40.

Hokuriku Journal of Anesthesiology
Anesthetic management of a patient with Charcot-Marie-Tooth disease by Shimo K; Shin-E S, et al. Hokuriku Journal of Anesthesiology 1998 32/1 (59-61)

ABSTRACT: Charcot-Marie-Tooth disease (CMT) is a hereditary degenerative disorder characterized by slowly progressive muscular atrophy of the extremities. There are many risks in the anesthetic management. The patients with CMT have a high sensitivity to thiopental, a prolonged response to muscle relaxants and autonomic disorder such as unstable hemodynamics. A 25-year-old man with CMT was scheduled for tarsal V osteotomy. Anesthesia was maintained with nitrous oxide in oxygen, fentanyl and propofol infusion. Vecuronium was injected according to NMT monitor. The operation was completed uneventfully and hemodynamics was stable intraoperatively. There was no prolonged response to propofol and vecuronium. In conclusion, anesthesia with propofol, fentanyl and vecuronium seems to be a good choice for the patients with CMT.

ANESTHETICS RESEARCH UPDATE re: THIOPENTAL
by Linda Crabtree

Another research paper stuck out in the long list of new articles printed and it was titled, Motor and Sensory Disability has a Strong Relationship to Induction Dose of Thiopental on Patients with the Hypertrophic Variety of Charcot-Marie-Tooth Syndrome by Naoki Kotani, MD, et al appearing in Anesthesia and Analgesia Vol. 82, No. 1 Jan. 1996.
I asked Dr. Joseph F. Antognini, Department of Anesthesiology, U.C. Davis Medical Center, Sacramento, California what he thought about the paper. He wrote:
"Patients with CMT often require surgery, usually for correction of orthopedic problems, but also for any of the other ailments which can afflict humans. CMT patients are understandably concerned about the effects of anesthesia on their disease. A recent article published by Kotani, et al, documented increased sensitivity to thiopental in patients with CMT. What does this mean for you, the CMT patient? Should you avoid thiopental? What are the alternatives?
"Thiopental is an intravenous anesthetic that has been used for decades to induce anesthesia. It is a short-acting barbiturate which induces unconsciousness within 15-30 seconds, when given in appropriate doses.
"A closer examination of the paper by Kotani, et al, reveals that although CMT patients appeared to be more sensitive to thiopental (required less to ‘go to sleep'), all patients except one woke up quickly at the end of surgery, and thiopental was not the reason why this lone patient didn't awaken quickly. Although there are some methodological weaknesses to this study, the conclusions are appropriate...regardless of the patient, the anesthetist should always give the "right" amount of drug for each individual patient.
"I don't think that thiopental needs to be avoided in the CMT patient as long as it is given appropriately. As I have mentioned before, there are alternatives to thiopental and general anesthesia. A regional anesthetic, such as a spinal, is often a good choice. Newer anesthetic drugs which permit faster recovery can be used. Nonetheless, thiopental is still a good choice, and I don't think that the paper by Kotani, et al, should dissuade you or your anesthetist from using it."

Anesthesia in neuromuscular disorders. Part 2: specific disorders

Baur CP, Schara U, Schlecht R, Georgieff M, Lehmann-Horn F. Anesthesia in
neuromuscular disorders. Part 2: specific disorders. Anasthesiol Intensivmed Notfallmed Schmerzther 2002 Mar;37 Universitatsklinik fur Anasthesiologie der Universitat Ulm.

The neuromuscular disorders described are divided into four groups: motoneuron diseases, peripheral neuropathies, disturbances of neuromuscular transmission and myopathies. In motoneuron diseases problems mainly result from respiratory insufficiency and the predisposition for aspiration caused by progressive muscular weakness. Depolarising muscle relaxants may elicit myotonic reaction and massive hyperkalemia. In contrast to non-depolarising muscle relaxants there may be an extreme hypersensitivity. In peripheral neuropathies the cardiac function is often limited whereby dysautonomia may enhance
cardiovascular instability. The negative inotropic effect of anaesthetic agents must be observed with care and patients with higher degree of AV blocks may need a cardiac pacemaker during general anaesthesia. The Charcot-Marie-Tooth-Syndrome is characterized with a high sensitivity to thiopental. Disturbances of neuromuscular transmission frequently cause
respiratory problems. The fluctuating weakness of bulbar and respiratory muscles may impair swallowing and can lead to recurrent aspirations. Due to the reduced number of acetylcholine receptors the sensitivity to non-depolarizing muscle relaxants is elevated and the response to succinylcholine is reduced. Drugs reducing neuromuscular transmission such as antibiotics and beta-blockers may enhance these symptoms and should be avoided. In progressive muscular
dystrophies the anaesthetic risk is mainly dependent on cardiac and respiratory impairment. Administration of succinylcholine leads to the risk of hyperkalmic cardiac arrest. Patients with metabolic myopathies are also at risk due to the involvement of cardiac muscle but respiratory problems are less frequent. Muscle metabolism should be supported by administration of substrates depending on the underlying disorder. In membrane disorders muscle rigidity (myotonic reactions) or weakness may lead to respiratory insufficiency. In addition to the depolarising muscle relaxants also anticholinesterase drugs, hypothermia and dyskalaemia can evoke myotonic reactions.

PMID: 11889613 [PubMed - in process]