Charcot–Marie–Tooth disease (CMTD) type 1A, also known as hereditary motor and sensory neuropathy, is an autosomal dominant demyelinating polyneuropathy with a total prevalence rate of 1 in 2500. Onset of CMTD usually occurs in the second decade of life. It is characterized by slowly progressive weakness and muscle atrophy, first affecting the lower extremities and later involving hands and forearms. Sensory alterations are usually milder than motor symptoms. Autonomic disturbances, such as hypotension, hypohidrosis and decreased skin temperature, are sometimes reported. Typical neurophysiological alteration is an increase in latency of evoked responses at both proximal and distal muscles as expression of the myelinopathy; a further prolongation in latency along with a decrease in response amplitude may also appear in distal muscles as a result of the secondary axonopathy.1
Obviously, succinylcholine use in patients with CMTD is associated with increased risk of malignant arrhythmias secondary to exaggerated hyperkalaemic response.2 Although succinylcholine has been used in these patients without untoward effects,3 it seems appropriate to avoid its use in any patient with suspected muscular denervation.
Nondepolarizing neuromuscular blocking drugs (NMBDs) have been used successfully in patients with CMTD without indications of prolonged duration of action.3 However, there is reasonable concern that some patients with CMTD may show an abnormal sensitivity in response to neuromuscular blockade (NMB).4 This case report describes cisatracurium-induced NMB during total intravenous anaesthesia in a patient with CMTD.
A 58 kg, 168 cm, 35-year-old female patient, known to have CMTD type 1A, was scheduled for diagnostic gynaecological laparoscopy. The CMTD had been diagnosed 4 years before when she underwent neurological examination following the occurrence of paraesthesias in all limb extremities along with nocturnal cramps. When she was 5 years old she had had surgical removal of a sixth toe. There was a history of the disease in the family: her mother had CMTD type 1A.
Neurological examination revealed a mild decrease in tendon reflexes in both upper and lower limbs. Electromyography showed signs of a demyelinizing neuropathy: decreased nervous conduction velocity – in both the right and left external popliteal sciatic nerves and left median nerve – at about 20 ms−1 with a prolongation of motor distal conduction time. The vital signs and results of laboratory tests were normal.
The patient did not receive anaesthetic premedication. On the patient's arrival in the operating theatre, electrocardiogram, peripheral oxygen saturation, noninvasive blood pressure, expired carbon dioxide, bispectral index (BIS) and temperature (by nasopharyngeal thermistor) were monitored. Neuromuscular monitoring was performed on the left arm using acceleromyography (TOF-Watch; Organon Teknika, Boxtel, The Netherlands). The adductor pollicis muscle was monitored with the piezoelectric ceramic wafer placed at the distal interphalangeal joint of the thumb. Repetitive train-of-four (TOF) stimulation of the ulnar nerve via surface stimulating electrodes placed on the wrist was used (four pulses of 0.2 ms in duration, at a frequency of 2 Hz every 15 s).
Anaesthesia was induced with fentanyl 2 μg kg−1 followed by propofol in target-controlled infusion (TCI) at a calculated effect-site concentration of 5 μg ml−1. Immediately after the patient's loss of consciousness, the automatic calibration set-up of the TOF-Watch was set to determine supramaximal stimulation (single twitch, 0.1 Hz). Following calibration, a signal stabilization phase for the control response was established over a period of 2 min. Thereafter, a bolus of cisatracurium 0.1 μg kg−1 was administered. When complete neuromuscular block (maximal depression of T1, the first twitch of TOF stimulation) was achieved, the trachea was intubated. Anaesthesia was maintained with propofol at a calculated effect-site concentration of 4 ± 0.5 μg ml−1 in order to maintain BIS below 60. A TCI Diprifusor device (AstraZeneca, Fresenius Vial SA, Brèzins, France) was used for propofol delivery. No supplementary doses of cisatracurium were administered. Ventilation was adjusted to maintain normocapnia (end-tidal partial pressure of carbon dioxide, range 35–40 mmHg).
The administered cisatracurium dose produced the first measurable effect (lag time) and the maximum neuromuscular block (onset time or maximal T1 depression) in 73 and 266 s, respectively. The maximum block attained was 98% inhibition of T1. Time until recovery of 25% of baseline amplitude of T1 was 32 min (clinical duration). At the end of surgery, which lasted 35 min, the TCI propofol infusion was stopped and a mixture of atropine 1 mg and neostigmine 2 mg was administered. The recovery index – time interval from the end of the clinical stage (T1 = 25%) to 75% recovery of T1 (T1 = 75%) – was 8 min. The time interval from the end of the clinical stage (T1 = 25%) to a TOF ratio of 0.90 was 12 min (recovery time).
After recovery of spontaneous diaphragmatic breathing with an adequate tidal volume, the tracheal tube was removed. The patient began to breathe spontaneously and woke up (eyes opening) at propofol effect-site concentrations of 1.6 μg ml−1 (BIS = 68) and 1.2 μg ml−1 (BIS = 77), respectively. Total propofol consumption was 764 mg. The values of noninvasive blood pressure and heart rate were stable during the whole intraoperative period. The 24 h postoperative course was uneventful.
Anaesthetic management of a rare disease is still a challenge for the practitioner. Pertinent information on this uncommon disease is essentially based on case reports or case series. To date, there have been few descriptions of anaesthetic management in patients with CMTD probably because many cases go unrecognized without uneventful complications. In this report, our patient with CMTD showed a normal response to cisatracurium in accordance with previous case reports that demonstrated little or no effect on pharmacodynamic parameters of NMBDs in this rare disease.5,6 One group of authors observed a normal response to both atracurium and mivacurium in a 17-year-old patient with CMTD who underwent anaesthesia on two occasions5 and another group of authors did not find a prolonged response to cisatracurium.6 However, Baraka7 noted a normal or even a relatively rapid rate of recovery from vecuronium-induced neuromuscular block in a 16-year-old patient with advanced CMTD. The author speculated that this could be due to the upregulation of acetylcholine receptors at the neuromuscular junction caused by a generalized polyneuropathy, even in the presence of weakness and muscle atrophy. On the other hand, Pogson et al.8 described the case of a patient with CMTD, in whom vecuronium produced prolonged neuromuscular block lasting 115 min. In another study, one of 20 prospectively investigated patients with CMTD scheduled for orthopaedic procedures, after receiving vecuronium 0.07 mg kg−1 at anaesthesia induction, did not exhibit spontaneous ventilation for 280 min.9
A useful clinical observation is that none of the patients who showed a normal response to NMBDs in the case reports cited above had any signs of diaphragmatic dysfunction.5,6 The safe use of NMBDs in most of the CMTD cases may, thus, depend on the fact that phrenic nerve involvement, which may cause diaphragmatic weakness, even in the early stages of the disease, occurs in rare types of CMTD.5 Fiacchino et al.,4 in a case report of unrecognized CMTD, stated that the use of NMBDs is safe probably because when denervation phenomena occur they are restricted to the distal segment of limbs. Any residual NMB in these segments is likely to be underestimated at the end of surgery due to its low clinical relevance.
As CMTDs are quite heterogeneous, the different stages of disease progression and also the different types of CMTD might explain the reported differences in response to NMBDs. Consequently, the anaesthetic management could be ideally adjusted to the needs of the individual patient on the basis of stage and type of the disease and symptom severity. However, the possibility of an occult pulmonary dysfunction should also be considered in asymptomatic patients.
The anaesthetic technique may also have such a role in affecting response to NMBDs. In the previously cited cases which reported a delay in recovery from NMB, volatile anaesthetics had been administered.8,9 Volatile anaesthetics may enhance the effects of NMBDs independently of their own muscle relaxant effects and this could result in unplanned prolongation of block. As this effect might be amplified by muscle weakness in patients with CMTD, volatile anaesthetics were specifically avoided in the present case.
Although in patients with neuromuscular disorders, such as myotonic dystrophia and progressive muscular dystrophy, the reverse of NMB may paradoxically worsen the block, this has not been reported in patients with CMTD. Neostigmine was used in the present case without adverse effects.
In conclusion, the evidence from this case report contributes to reassure anaesthesiologists about the safe use of NMBDs in patients with CMTD. However, a continuous monitoring of NMB should always be performed and prudence must be used in those rare cases in which denervation affects respiratory muscles. Finally, it is preferable to perform NMB monitoring at the adductor pollicis, a muscle probably less affected, or that is affected later in the progression of CMTD, than lower limb muscles.
1 Houlden H, Reilly MM. Molecular genetics of autosomal-dominant demyelinating Charcot-Marie-Tooth disease. Neuromolecular Med 2006; 8:43–62.
2 Martyn JA, Richtsfeld M. Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms. Anesthesiology 2006; 104:158–169.
3 Antognini JF. Anaesthesia for Charcot-Marie-Tooth disease: a review of 86 cases. Anesthetic management in Charcot-Marie-Tooth disease. Can J Anaesth 1992; 39:398–400.
4 Fiacchino F, Grandi L, Ciano C, Sghirlanzoni A. Unrecognized Charcot-Marie-Tooth disease: diagnostic difficulties in the assessment of recovery from paralysis. Anesth Analg 1995; 81:199–201.
5 Naguib M, Samarkandi AH. Response to atracurium and mivacurium in a patient with Charcot-Marie-Tooth disease. Can J Anaesth 1998; 45:56–59.
6 García-Ferreira J, Hernández-Palazón J. Response to cisatracurium in patient with Charcot-Marie-Tooth disease. Eur J Anaesthesiol 2005; 22:160–161.
7 Baraka AS. Vecuronium neuromuscular block in a patient with Charcot-Marie-Tooth syndrome. Anesth Analg 1997; 84:927–928.
8 Pogson D, Telfer J, Wimbush S. Prolonged vecuronium neuromuscular blockade associated with Charcot Marie Tooth neuropathy. Br J Anaesth 2000; 85:914–917.
9 Kotani N, Hirota K, Anzawa N, et al
. Motor and sensory disability has a strong relationship to induction dose of thiopental in patients with the hypertropic variety of Charcot-Marie-Tooth syndrome. Anesth Analg 1996; 82:182–186.