1Department of Anesthesiology and Intensive Care Medicine, Kanazawa University School of Medicine, Kanazawa, Japan. 2Department of Emergency and Critical Care Medicine, Kanazawa University School of Medicine, Kanazawa, Japan. 3Division of Anesthesia, Ishikawa Prefectural Central Hospital, Kanazawa, Japan*Corresponding author: Department of Anesthesiology and Intensive Care Medicine, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan
Accepted for publication: July 23, 2001
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Br J Anaesth 2001; 87: 8859
Keywords: equipment, force transducer; complications, myasthenia gravis; neuromuscular block, Osserman classification
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Binding and blocking antibodies to AChR were measured preoperatively in serum samples. To determine binding antibody, -bungarotoxin labelled with 125I was bound to prepared antigenic human AChR (125I-AChR). Sera from patients were incubated with 125I-AChR. Antigenantibody complexes were precipitated by incubation with anti-human IgG. Radioactivity in the precipitate was measured with a gamma counter.8 When measuring binding antibody, it is impossible to detect the antibody in the area near the acetylcholine binding site of the receptor. Thus, blocking antibody to the acetylcholine binding site was also measured. Sera from patients and controls were incubated with prepared antigenic AChR followed by incubation with 125I-labelled
-bungarotoxin. Aliquots were then applied to Sepharose columns to measure the percentage inhibition of labelled toxin binding with AChR.9
Anticholinesterase medication was continued until the morning of surgery. The patients were premedicated with hydroxyzine 50 mg and atropine 0.5 mg, given 1 h before induction of anaesthesia. Anaesthesia was induced with thiopental 4 mg kg1 and fentanyl 2 µg kg1 followed by inhalation of sevoflurane 2.5% and nitrous oxide 60% in oxygen. The lungs were ventilated by face-mask so that the end-tidal carbon dioxide pressure was maintained at about 5.3 kPa. Skin temperature over the thenar region was monitored and was maintained at 3233°C. Non-invasive blood pressure was measured every 5 min, and when systolic blood pressure had decreased to <80 mm Hg ephedrine 5 mg was administered i.v.
Neuromuscular transmission was monitored by measuring twitch tension in the adductor pollicis muscle (Myograph 2000; Biometer International, Odense, Denmark). The ulnar nerve was stimulated at the wrist using surface electrodes with supramaximal train-of-four (TOF) square-wave pulses of duration 0.2 ms every 12 s (Myotest, Biometer International). When the twitch response had remained stable for at least 10 min, the baseline height of the first twitch (T1) was measured. The TOF ratio, expressed as a percentage, was defined as the ratio of the fourth to the first response to TOF stimulation. After baseline measurements, an initial dose of vecuronium 10 µg kg1 was administered i.v. Maximum block was defined as the maximum effect of the first dose of vecuronium 10 µg kg1. The next incremental dose of vecuronium 10 µg kg1 was given after the twitch had again stabilized. As long as neuromuscular block, defined as [1(T1/baseline T1)]x100, was less than 90%, additional doses of vecuronium were given until 90% or greater block had been achieved. The trachea was then intubated and the inspired concentration of sevoflurane was decreased from 2.5% to between 0.5 and 1.5%. Responses in the adductor pollicis muscle were monitored continuously. Maximum block produced by vecuronium 10 µg kg1 and the time to the onset of maximum block were recorded.
Statistics
Parametric data are presented as mean (SD) and non-parametric data as median (range). Parametric data were analysed with the t test and non-parametric data with the MannWhitney U test. A P value less than 0.05 was considered to indicate significance.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
As sensitivity to non-depolarizing neuromuscular blocking drugs is increased in myasthenic patients,16 we used an initial dose of vecuronium 10 µg kg1, which is smaller than the priming dose used ordinarily.12 13 Sensitivity to non-depolarizing neuromuscular blocking drugs is known to vary greatly between myasthenic patients. Several studies using a cumulative technique have shown the ED95 for vecuronium to range from 6 to 44 µg kg1.2 3 Although one patient in our ocular group showed 98% block with vecuronium 10 µg kg1, exceeding the median value for maximal block in the generalized group, the ocular myasthenic patients as a whole showed less sensitivity to vecuronium than the generalized myasthenic patients.
In myasthenia gravis, the ocular muscles are affected most commonly, being involved initially in 40% of cases. It is rare for the initial symptoms to be limited to limb muscles.6 However, intraoperative neuromuscular monitoring is commonly performed in the upper limb. Our data show that the limb muscles of ocular myasthenic patients are significantly less sensitive to vecuronium than those of generalized myasthenic patients. Differences in sensitivity between ocular and generalized myasthenia gravis patients probably occur because the disease induces different degrees of change in the margin of safety for neuromuscular transmission in the limb muscles. In ocular patients, clinically important decreases in this margin of safety occur only in ocular muscles. In contrast, generalized myasthenic patients show a decreased margin of safety in all skeletal muscles, including the adductor pollicis.
The ED50 for vecuronium has ranged from 0.3 to 19 µg kg1 and the ED90 from 5 to 35 µg kg1 in myasthenic patients.13 In these studies, most patients represented type II in the Osserman classification, like the patients with generalized myasthenia in our study. Additionally, type IV patients (with late, severe generalized myasthenia) were included in the study of Eisenkraft and colleagues.2 Only one patient of this type was studied by Buzello and colleagues.1 Patients in our generalized group were similar in disease severity to most subjects in previous studies. However, patients in our ocular group had milder myasthenia than the individuals studied previously. Although we did not calculate effective doses of vecuronium, our data showed a difference in sensitivity between ocular and generalized patients.
Our data were obtained under nitrous oxidesevoflurane anaesthesia; in previous reports of myasthenic patients, neuromuscular variables were measured in the absence of potent anaesthetic agents. Generally, inhaled anaesthetics decrease the availability of acetylcholine at the neuromuscular junction14 and increase the neuromuscular block produced by non-depolarizing neuromuscular blocking drugs,1517 but this effect has not been specifically confirmed in myasthenic patients. Vanlinthout and colleagues15 reported ED50 and ED95 values for vecuronium in neurologically healthy patients during anaesthesia with sevoflurane 1.7% of 14.4 and 34.9 µg kg1 respectively, which are 42 and 32% less than when inhaled anaesthetics are not used. The generalized myasthenic patients in this study, who were apparently similar to the myasthenic patients in previous studies of vecuronium, showed 91% block from vecuronium 10 µg kg1. Although comparisons between studies have limitations, the block produced appeared to be greater in our study than in previous studies of myasthenia gravis; the sensitivity to vecuronium was probably increased by sevoflurane in myasthenic patients as well as in our patients with normal neuromuscular transmission.
However, the use of inhalational anaesthetics does not affect the results of this study, which compared the sensitivity to vecuronium of two types of myasthenia. One limitation of this study, however, may be that we did continue the morning dose of anticholinesterase. The incidence of TOF fade before administration of vecuronium, which is well tolerated in myasthenia gravis patients, was low in our patients; this may have been caused by the administration of pyridostigmine. The other limitation was the interval between TOF stimuli. It has not been established in patients with myasthenia gravis that an interval as long as 12 s between TOF stimuli is sufficient. The twitches may thus have been affected by preceding stimuli. We standardized the interval at 12 s, as used in neurologically healthy patients, as any effect of myasthenia in this respect has not been shown.
In summary, we estimated neuromuscular block produced by vecuronium in the adductor pollicis muscle in patients with ocular and generalized myasthenia. Ocular myasthenic patients were less sensitive to vecuronium than generalized myasthenic patients. During general anaesthesia, neuromuscular monitoring is essential to avoid problems of prolonged neuromuscular block in myasthenic patients; however, the degree of block produced by a given dose of vecuronium is likely to be less in ocular than in generalized myasthenic patients.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Eisenkraft JB, Book WJ, Papatestas AE. Sensitivity to vecuronium in myasthenia gravis: a doseresponse study. Can J Anaesth 1990; 37: 3016[Abstract]
3 Nilsson E, Meretoja OA. Vecuronium doseresponse and maintenance requirements in patients with myasthenia gravis. Anesthesiology 1990; 73: 2832[ISI][Medline]
4 Baraka A, Tabboush Z. Neuromuscular response to succinylcholinevecuronium sequence in three myasthenic patients undergoing thymectomy. Anesth Analg 1991; 72: 82730[ISI][Medline]
5 Seigne RD, Scott RP. Mivacurium chloride and myasthenia gravis. Br J Anaesth 1994; 72: 4689[Abstract]
6 Miller JD, Lee C. Muscle Disease. In: Katz J, Benumof JL, Kadis LB, eds. Anesthesia and Uncommon Disease, 3rd Edn. Philadelphia: W. B. Saunders, 1990; 590644
7 Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 1971; 38: 497537[ISI][Medline]
8 Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to acetylcholine receptor in myasthenia gravis: prevalence, clinical correlates, and diagnostic value. Neurology 1976; 26: 10549[Abstract]
9 Mittag T, Kornfeld P, Tormay A, Woo C. Detection of anti-acetylcholine receptor factors in serum and thymus from patients with myasthenia gravis. N Engl J Med 1976; 294: 6914[Abstract]
10 Itoh H, Shibata K, Yoshida M, Yamamoto K. Neuromuscular monitoring at the orbicularis oculi may overestimate the blockade in myasthenic patients. Anesthesiology 2000; 93: 11947[ISI][Medline]
11 Mann R, Blobner M, Jelen-Esselborn S, Busley R, Werner C. Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients. Anesthesiology 2000; 93: 34650[ISI][Medline]
12 Brady MM, Mirakhur RK, Gibson FM. Influence of priming on the potency of non-depolarizing neuromuscular blocking agents. Br J Anaesth 1987; 59: 12459[Abstract]
13 Martin C, Bonneru JJ, Brun JP, Albanese J, Gouin F. Vecuronium or suxamethonium for rapid sequence intubation: which is better? Br J Anaesth 1987; 59: 12404[Abstract]
14 Waud BE, Waud DR. The effects of diethylether, enflurane, and isoflurane at the neuromuscular junction. Anesthesiology 1975; 42: 27580[ISI][Medline]
15 Vanlinthout LE, Booij LH, van Egmond J, Robertson EN. Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium. Br J Anaesth 1996; 76: 38995
16 Taivainen T, Meretoja OA. The neuromuscular blocking effects of vecuronium during sevoflurane, halothane and balanced anaesthesia in children. Anaesthesia 1995; 50: 10469[ISI][Medline]
17 Suzuki T, Munakata K, Watanabe N, Katsumata N, Saeki S, Ogawa S. Augmentation of vecuronium-induced neuromuscular block during sevoflurane anaesthesia: comparison with balanced anaesthesia using propofol or midazolam. Br J Anaesth 1999; 83: 4857