CJA
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Résumé de cet Article
Right arrow Full Text (PDF)
Right arrow Submit a scholarly reply
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Saitoh, Y.
Right arrow Articles by Murakawa, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saitoh, Y.
Right arrow Articles by Murakawa, M.
Canadian Journal of Anesthesia 52:467-473 (2005)
© Canadian Anesthesiologists' Society, 2005
General Anesthesia

Delayed recovery of vecuronium neuromuscular block in diabetic patients during sevoflurane anesthesia

[Bloc neuromusculaire au vécuronium prolongé chez des patients diabétiques pendant l’anesthésie au sévoflurane]

Yuhji Saitoh, MD*, Hisashi Hattori, MD{dagger}, Norie Sanbe, MD{dagger}, Hiroshi Nakajima, MD{dagger}, Masahiko Akatu, MD{dagger} and Masahiro Murakawa, MD{dagger}

* From the Department of Anesthesiology, Saitama Medical School, Saitama; and
{dagger} the Department of Anesthesiology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Address correspondence to: Dr. Yuhji Saitoh, Saitama Medical School Department of Anesthesiology, 38, Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan. Phone: +81-49-276-1271; Fax +81-49-295-8077; E-mail: ysys{at}r5.dion.ne.jp


   Abstract
TOP
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Purpose: To study recovery from vecuronium-induced neuromuscular block in diabetic patients during total iv or sevoflurane anesthesia.

Methods: 30 diabetic patients were assigned to diabetes mellitus (DM)-total iv anesthesia (TIVA); (n = 15) or DM-sevoflurane (S) groups (n = 15). Thirty healthy patients were divided into control-TIVA (n = 15) or control-S groups (n = 15). In the DM-TIVA or control-TIVA groups and DM-S or control-S groups, anesthesia was maintained with propofol and fentanyl, and nitrous oxide-oxygen-sevoflurane 1.7%, respectively. After receiving vecuronium 0.1 mg·kg–1iv, recovery of the train-of-four (TOF) was compared among the four groups.

Results: Times to the return of T2, T3, or T4 in the DM-TIVA and DM-S groups were longer than in the control-TIVA and control-S groups (46.9 ± 13.8 vs 32.2 ± 10.7 and 32.6 ± 8.7 min for T2, P < 0.05). T1/control in the DM-S group was less than in the control-TIVA and DM-TIVA groups 50 to 120 and 70 to 120 min after receiving vecuronium, respectively (P < 0.05). T1/control in the control-S group was less than in the control-TIVA group 80 to 120 min after receiving vecuronium (P < 0.05). TOF ratio in the DM-S group was less than in the control-TIVA, DM-TIVA, and control-S groups, 60 to 120, 80 to 120, and 80 to 120 min after receiving vecuronium, respectively (P < 0.05).

Conclusion: In diabetic patients receiving vecuronium, recovery of T1/control and TOF ratio are delayed during sevoflurane anesthesia, but not in association with total iv anesthesia.


   Introduction
TOP
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
WE have shown previously that recovery from neuromuscular blockade caused by vecuronium is delayed in diabetic patients.1 This is probably because patients with diabetes mellitus exhibit degeneration, demyelination, or axon loss in the motor nerve ending of the neuromuscular junction, and infarction or atrophy in the skeletal muscle ensues.2–10 In the previous study,1 patients were anesthetized with nitrous oxide, oxygen, and isoflurane at an end-tidal concentration of 0.5%. Inhalation anesthetics enhance the action of neuromuscular relaxants by acting at the neuromuscular junction.11,12 In fact, recovery from neuromuscular block is delayed in patients anesthetized with inhalation anesthetics.11,12 In contrast, iv anesthetics, do not potentiate the action of neuromuscular relaxants.13–15 However, the time course of recovery from neuromuscular blockade is variable under different types of anesthesia in healthy patients.11,12 As motor nerves and skeletal muscles are damaged in diabetic patients, the degree of potentiation by inhalation anesthetics may differ from that observed in healthy patients. However, no previous study has investigated recovery from neuromuscular blockade in diabetic patients receiving total iv anesthesia. This study was therefore undertaken to document recovery from vecuronium in patients with diabetes during iv anesthesia and sevoflurane anesthesia.


   Methods
TOP
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
This work was done in the Department of Anesthesiology, Fukushima Medical University School of Medicine. The protocol was approved by our Institutional Ethics Committee. Written informed consent was obtained from each patient. Thirty adult patients, ASA physical status II or III, who had had type 2 diabetes mellitus for more than three years, and 30 adult patients, ASA I to II without diabetes mellitus were studied. The ideal number of patients based upon previous data is represented as 2 x SD2 x (power index) ÷ (difference).2,27 If {alpha}1 and 1-ß are 0.10 and 0.80, respectively, when time to the return of T1, T2, T3, or T4 is compared statistically between the two groups, the ideal numbers of patients should be 17.2. Similarly, when T1/control and the TOF ratio is compared, the ideal numbers of patients are 49.6 and 12.4, respectively. Thus, in the present study, the number of patients was within the permissible range for comparison of the time to the return of T1, T2, T3, or T4, and that of the TOF ratio.

The diagnosis of diabetes had been established in the Department of Internal Medicine of our institution. The criteria used to classify the patients as type 2 diabetes were fasting plasma glucose repeatedly > 17.8 mmol·L–1, or a two-hour plasma glucose > 11.1 mmol·L–1 after a 75 g glucose load. An additional criterion was that no patient had a history of diabetic ketoacidosis or a hyperglycemic hyperosmolar state. These criteria were in accordance with a previous report.16 The patients were scheduled for elective orthopedic surgery (total hip replacement), ear nose and throat surgery (tympanoplasty), or ophthalmological surgery (segmental buckling or vitrectomy) under general anesthesia. The 30 patients with diabetes were randomly assigned to diabetes mellitus (DM)-total iv anesthesia (TIVA) group (n = 15) or DM-sevoflurane (S) group (n = 15). The 30 healthy patients were randomly divided into two groups of 15 patients each: control-TIVA or control-S groups. All patients in the DM-TIVA and DM-S groups had been treated for diabetes for three to 12 yr. The patients in the DM-TIVA and DM-S groups had had type 2 diabetes mellitus for 7.8 ± 2.9 and 7.7 ± 2.9 yr (mean ± SD, P = 0.922), respectively. All patients in the DM-TIVA and DM-S groups were receiving glibenclamide 2.5 to 7.5 mg a day orally. In five and six patients in the DM-TIVA and DM-S groups, respectively, the total number of calories ingested was reduced to 1400–1800 kcal·day–1. Three and three patients in the DM-TIVA and DM-S groups received sc injection of neutral insulin 10 to 26 U·day–1, respectively. Two to five days before the surgical procedure, in the diabetic patients, the oral administration of glibenclamide was changed to a continuous iv infusion of neutral insulin 10 to 24 U·day–1, which maintained the blood sugar level between 5.8 to 13.4 mmol·L–1. The diabetic patients were consulted and treated by internists in our institution. The internists confirmed that all patients in the DM-TIVA and DM-S groups were free from diabetic neuropathy and nephropathy. No patient in the four groups had neuromuscular, hepatic, renal, or cardiac disorders, and none was receiving medications known to interfere with the action of neuromuscular blocking drugs.

Diazepam 0.1 mg·kg–1 was given orally 60 min before induction of anesthesia in all patients. After arriving in the operating room, two stimulating electrodes were positioned over the ulnar nerve at the wrist. Two recording electrodes were attached over the adductor pollicis muscle. In the DM-TIVA and control-TIVA groups, anesthesia was induced with a continuous infusion of propofol using a target-controlled-infusion device (Terufusion TCI pump, Terumo Inc., Tokyo, Japan) utilizing the pharmacokinetic model as reported previously17,18 and a bolus injection of fentanyl 2 µg·kg–1 iv. The target blood concentration of propofol was initially set to 3.5 µg·mL–1 and then progressively decreased by steps of 0.5 µg·mL–1. During the surgical procedure, the target blood concentration of propofol was maintained at 2.5 or 3.0 µg·mL–1. In the DM-S and control-S groups, anesthesia was induced with thiopental 5.0 mg·kg–1 iv and fentanyl 2 µg·kg–1 iv. In all groups, after the loss of eyelid reflex, train-of-four (TOF) stimuli were applied every 20 sec using an electrical nerve stimulator of an anesthetic monitoring system (AS/3 Compact Monitor, Datex-Ohmeda Inc., Helsinki, Finland). Four single twitch stimuli consisting of 0.2 msec duration square-waves were applied at 2 Hz. The corresponding electromyographic amplitudes were quantified using the neuromuscular transmission module, and were displayed on the anesthetic monitoring system. The monitoring system searched for the stimulus current needed to achieve the maximal response of the adductor pollicis muscle. If the supramaximal current was not found or the response was too weak to determine the current, the current was set at 70 mA.

Once the supramaximal current had been established, the electromyographic amplitude of T1 was regarded as the control. The control value was again determined ten minutes after starting TOF stimuli, which were delivered every 20 sec, as has been recommended previously.19–21 During the ten minutes for the stabilization of neuromuscular monitoring, the patients’ lungs were ventilated using a facemask with oxygen 6 L·min–1, and oxygen 6 L·min–1 in combination with sevoflurane 2% in the TIVA groups and the S groups, respectively. After recording control values, vecuronium 0.1 mg·kg–1 iv was administered to facilitate tracheal intubation.

Times from vecuronium administration to the return of T1, T2, T3, and T4 (the first, second, third, and fourth response of the TOF) were compared amongst the four groups. Additionally, T1/control or TOF ratio were recorded every ten minutes and were compared amongst the four groups.

In the DM-TIVA and control-TIVA groups, the lungs were ventilated with air 5 L·min–1, oxygen 1 L·min–1, and anesthesia consisted of a TCI with propofol and a second bolus of fentanyl 5 µg·kg–1 iv. Whenever the anesthetic level was deemed to be insufficient, a bolus of fentanyl 2 µg·kg–1 iv was administered. In the DM-S and control-S groups, anesthesia was maintained with nitrous oxide 4 L·min–1, oxygen 2 L·min–1, and sevoflurane at an end-tidal concentration of 1.7%. In the DM-S and control-S groups, a bolus of fentanyl 2 µg·kg–1 iv was given when the anesthetic level was insufficient. In the four groups, ventilation was controlled to maintain normocapnia (PETCO2 32–36 mmHg). The end-tidal concentrations of anesthetic and PETCO2 were measured continuously, and were maintained constant throughout the surgical procedure. At the end of surgery, if the TOF ratio did not reach 0.9, neostigmine 0.04 mg·kg–1 iv in combination with atropine 0.02 mg·kg–1 iv was given to antagonize the residual neuromuscular block.

All results are expressed as number or mean ± SD. Patient characteristics, the supramaximal stimulating currents, and the times to the return of T1, T2, T3, or T4 were compared among the four groups using one-way ANOVA for repeated measures and Scheffe’s multiple comparison. Time courses of recovery of T1/control or TOF ratio were compared using two-way ANOVA for repeated measures followed by Scheffe’s multiple comparison to investigate differences among the groups at each time point. A P value < 0.05 was considered statistically significant. Statistical analyses were performed using SYSTAT 8.0 (SPSS Inc., Chicago, USA).


   Results
TOP
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Patient characteristics did not differ among the four groups. Supramaximal stimulating current in the DM-TIVA or DM-S group was higher than in the control-TIVA or control-S group (P < 0.05), (Table IGo). A supramaximal stimulating current could not be determined between 10 to 70 mA in one and two patients in the DM-TIVA and DM-S groups respectively.


View this table:
[in this window]
[in a new window]
  		TABLE I Patient characteristics and supramaximal stimulating current in the four groups
 
Time from vecuronium administration to the return of T1 did not differ among the four groups. However, times to the return of T2, T3, and T4 in the DM-TIVA and DM-S groups were longer than in the control-TIVA and control-S groups (P < 0.05), (Table IIGo).


View this table:
[in this window]
[in a new window]
  		TABLE II Times from vecuronium 0.1 mg·kg–1 to the return of T1, T2, T3, and T4 in the four groups
 
As shown in Figure 1Go, T1/control in the DM-S group was less than in the control-TIVA and DM-TIVA groups, 50 to 120 and 70 to 120 min after vecuronium administration, respectively (P < 0.05). T1/control in the control-S group was less than in the control-TIVA group 80 to 120 min after vecuronium (P < 0.05). As shown in Figure 2Go, the TOF ratio in the DM-S group was less than in the control-TIVA, DM-TIVA, and control-S groups, 60 to 120, 80 to 120, and 80 to 120 min after vecuronium, respectively (P < 0.05). Thus, the TOF ratio recovered more slowly in diabetic patients undergoing sevoflurane anesthesia.



View larger version (23K):
[in this window]
[in a new window]
  		FIGURE 1 Recoveries of T1/control after administration of vecuronium 0.1 mg·kg–1 in the DM-TIVA (dark circles), control-TIVA (empty circles), DM-S (dark squares), and control-S (empty squares) groups. Values are mean (SEM). *P < 0.05 DM-S group vs control-TIVA group. #P < 0.05 DM-S group vs DM-TIVA group. *P < control-S group vs control-TIVA group. DM = diabetes mellitus; TIVA = total iv anesthesia; S = sevoflurane.

 


View larger version (22K):
[in this window]
[in a new window]
  		FIGURE 2 Recoveries of TOF ratio after administration of vecuronium 0.1 mg·kg–1 in the DM-TIVA (dark circles), control-TIVA (empty circles), DM-S (dark squares), and control-S (empty squares) groups. Values are mean (SEM). *P < 0.05 DM-S group vs control-TIVA group. #P < 0.05 DM-S group vs DM-TIVA group. *P < 0.05 DM-S group vs control-S group. DM = diabetes mellitus; TIVA = total iv anesthesia; S = sevoflurane.

 
In two and two patients in the DM-TIVA and DM-S groups respectively, systolic arterial pressure decreased to less than 80 mmHg just before tracheal intubation. It returned to more than 100 mmHg after the trachea was intubated. None of the others demonstrated severe hypertension (systolic arterial pressure > 200 mmHg) or hypotension (systolic arterial pressure < 80 mmHg), severe tachycardia (heart rate > 120 beats·min–1), or severe bradycardia (heart rate < 50 beats·min–1). In no patient did the peripheral temperature over the adductor pollicis muscle and the rectal temperature decrease to less than 32 and 35.5°C, respectively. At the end of the surgical procedure, neostigmine 0.04 mg·kg–1 iv in combination with atropine 0.02 mg·kg–1 iv was administered when the TOF ratio was less than 0.9. Thereafter, the TOF ratio recovered to a value of more than 0.9 in all patients in the four groups.


   Discussion
TOP
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
This study indicates that after the administration of vecuronium, return of T2, T3, or T4 in diabetic patients under sevoflurane anesthesia is delayed as compared with that in healthy patients under total iv anesthesia or sevoflurane anesthesia. T1/control amplitude during sevoflurane anesthesia is lower than during total iv anesthesia, but it is not affected by the presence of diabetes mellitus. The TOF ratio in diabetic patients anesthetized with sevoflurane is lower than that in healthy patients under total iv or sevoflurane anesthesia and diabetic patients under total iv anesthesia. When anesthetized with propofol and fentanyl, even in diabetic patients, recovery of TOF ratio does not differ from that in healthy patients under total iv or sevoflurane anesthesia.

In patients with diabetes mellitus, nerve endings at the neuromuscular junction are thought to degenerate.2 Additionally, demyelination and axon loss are observed in the nerve endings in diabetic patients.3 Savarese et al.22 reported that the response to non-depolarizing neuromuscular blocking drugs was exaggerated in patients with motor neuron disease. We also reported that recovery from neuromuscular blockade caused by vecuronium was slower in diabetic patients than in healthy patients anesthetized with isoflurane.1 Impairment of the skeletal muscle has also been shown in diabetic patients. Muscular infarction, aseptic myonecrosis, ischemic myonecrosis, focal muscular degeneration, and muscular atrophy have been reported in diabetic patients.7–10 These pathophysiological changes would be based upon arteriosclerosis, true sclerotic obliterans, and autoimmune phenomena.7

In our previous study,1 the return of T1, T2, T3, or T4, and recovery of T1/control were delayed in diabetic patients, but recovery of the TOF ratio did not differ between diabetic and healthy patients. It has been reported that the time to the return of T1, T2, T3, or T4, and recovery of T1/control represents the degree of neuromuscular block at the postjunctional region of the neuromuscular junction, i.e., muscular membrane.11,12,23 In contrast, the TOF ratio is thought to relate to the level of neuromuscular block at the prejunctional region of the neuromuscular junction, i.e., nerve endings.11,12,23 As noted above, in our previous study,1 the return of T1, T2, T3, or T4, and recovery of T1/control were delayed, but recovery of the TOF ratio was not altered in diabetic patients. From these findings, therefore, we proposed that the damage of the postjunctional region of the neuromuscular junction would be more apparent than that of the prejunctional region. We expected that the return of T1, T2, T3, or T4, and recovery of T1/control would be delayed in diabetic patients.

Contrary to this expectation, in the current study, the recovery of T1/control was not slower in diabetic patients although return of T2, T3, or T4 was delayed. Furthermore, this study shows that recovery of the TOF ratio was delayed in diabetic patients anesthetized with sevoflurane. Therefore, the use of sevoflurane at an end-tidal concentration of 1.7% may slow recovery from neuromuscular block by acting mainly at the prejunctional region of the neuromuscular junction rather than at the postjunctional region. In fact, Lowry et al.24 studied time of the recovery of the TOF ratio to 0.80 among patients anesthetized with sevoflurane or isoflutrane compared to patients undergoing TIVA after the administration of rocuronium. In their study, sevoflurane, but not isoflurane prolonged the time of the recovery of the TOF ratio to 0.80. Wulf et al.25 also showed that the time required for the TOF ratio to recover 0.70 was prolonged in patients under sevoflurane anesthesia as compared to patients under isoflurane or propofol-fentanyl anesthesia after administration of cisatracurium. We hypothesized that recovery of the TOF ratio would be delayed under sevoflurane anesthesia.

As described above, time to the return of T1 did not differ among the four groups, but times to return of T2, T3, and T4 were prolonged in diabetic patients under sevoflurane anesthesia as compared to healthy patients under total iv and sevoflurane anesthesia. We are unable to fully explain this observation. However, we previously studied recovery of post-tetanic count (PTC) in diabetic and non-diabetic patients.1 In the previous study the recovery of PTC did not differ between diabetic and healthy patients.11 PTC is a monitoring method for evaluating intense neuromuscular block. When muscular response to T1 appears after the administration of a neuromuscular relaxant, the degree of neuromuscular block is also profound. Accordingly, when the level of neuromuscular blockade is intense, i.e., when response to T1 is barely elicited, recovery from neuromuscular block may be similar in diabetic and healthy patients. In contrast, if the degree of neuromuscular block subsides a response to T2, T3, or T4 becomes detectable, the return of T2, T3, or T4 would be delayed in diabetic patients as compared with healthy patients.

We assessed the level of neuromuscular block electromyographically. Kopman26 showed that, after the administration of atracurium, T1/control and the TOF ratio measured electromyographically were slightly greater than when evaluated mechanically using a force transducer. He also observed that even when neuromuscular block achieved partial recovery, the electromyographic T1/control often did not exceed a value of 0.85. Thus, T1/control and the TOF ratios evaluated in this study may be different from those assessed mechanically. In contrast, the number of patients would be too few to compare the difference in T1/control.

In conclusion, the return of T2, T3, or T4 in diabetic patients receiving vecuronium under sevoflurane anesthesia is delayed as compared with that in healthy patients under total iv anesthesia or sevoflurane anesthesia. Recovery of T1/control is slower during sevoflurane anesthesia than during total iv anesthesia, but is not altered by diabetes mellitus. Recovery of the TOF ratio does not differ between diabetic patients anesthetized with total iv anesthesia and healthy patients undergoing TIVA or sevoflurane anesthesia. Recovery of the TOF ratio is, however, delayed in diabetic patients anesthetized with sevoflurane.


   Footnotes
 
Accepted for publication April 26, 2004. Revision accepted February 8, 2005.


   References
TOP
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Saitoh Y, Kaneda K, Hattori H, Nakajima H, Murakawa M. Monitoring of neuromuscular block after administration of vecuronium in patients with diabetes mellitus. Br J Anaesth 2003; 90: 480–6.[Abstract/Free Full Text]

2 Woolf AL, Malins JM. Changes in the intramuscular nerve endings in diabetic neuropathy: a biopsy study. J Pathol Bacteriol 1957; 73: 316–8.

3 Lawrence DG, Locke S. Motor nerve conduction velocity in diabetes. Arch Neurol 1961; 5: 483–9.

4 Skillman TG, Johnson EW, Hamwi GJ, Driskill HJ. Motor nerve conduction velocity in diabetes mellitus. Diabetes 1961; 10: 46–51.

5 Abu-Shakra SR, Cornblath DR, Avila OL, et al. Conduction block in diabetic neuropathy. Muscle & Nerve 1991; 14: 858–62.[Medline]

6 Lamontagne A, Buchthal F. Electrophysiological studies in diabetic neuropathy. J Neurol Neurosurg Psychiat 1970; 33: 442–52.[Medline]

7 Van Slyke MA, Ostrov BE. MRI evaluation of diabetic muscle infarction. Magn Reson Imaging 1995; 13: 325–9.[Medline]

8 Rocca PV, Alloway JA, Nashel DJ. Diabetic muscle infarction. Semin Arthritis Rheum 1993; 22: 280–7.[Medline]

9 Eady JL, Cobbs KF. Diabetic muscle infarction. J South Orthop Assoc 1997; 6: 250–5.[Medline]

10 Scully RE, Mark EJ, McNeely WF, McNeely BU. Case records of the Massachusetts General Hospital. N Engl J Med 1987; 316: 1326–35.[Medline]

11 Saitoh Y, Toyooka H, Amaha K. Recoveries of post-tetanic twitch and train-of-four responses after administration of vecuronium with different inhalation anaesthetics and neuroleptanaesthesia. Br J Anaesth 1993; 70: 402–4.[Abstract/Free Full Text]

12 Saitoh Y, Toyooka H, Amaha K. Relationship between post-tetanic twitch and single twitch response after administration of vecuronium. Br J Anaesth 1993; 71: 443–4.[Abstract/Free Full Text]

13 Motamed C, Donati F. Sevoflurane and isoflurane, but not propofol, decrease mivacurium requirements over time. Can J Anesth 2002; 49: 907–12.[Abstract/Free Full Text]

14 Dragne A, Varin F, Plaud B, Donati F. Rocuronium pharmacokinetic-pharmacodynamic relationship under stable propofol or isoflurane anesthesia. Can J Anesth 2002; 49: 353–60.[Abstract/Free Full Text]

15 Woloszczuk-Gebicka B. Mivacurium infusion requirement and spontaneous recovery of neuromuscular transmission in children anaesthetized with nitrous oxide and fentanyl, halothane, isoflurane or sevoflurane. Paediatr Anaesth 2002; 12: 511–8.[Medline]

16 Bennett PH. Definition, diagnosis, and classification of diabetes mellitus and impaired glucose tolerance. In: Kahn CR, Weir GC (Eds). Joslin’s Diabetes Mellitus, 13th ed. Pennsylvania: Lea & Febiger; 1994: 193–200.

17 Gepts E. Pharmacokinetic concepts for TCI anaesthesia. Anaesthesia 1998; 53(Suppl 1): 4–12.

18 Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 41–8.[Abstract/Free Full Text]

19 Viby-Mogensen J, Engbaek J, Eriksson LI, et al. Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents. Acta Anaesthesiol Scand 1996; 40: 59–74.[Medline]

20 Lee GC, Iyengar S, Szenohradszky J, et al. Improving the design of muscle relaxant studies. Stabilization period and tetanic recruitment. Anesthesiology 1997; 86: 48–54.[Medline]

21 McCoy EP, Mirakhur RK, Connolly FM, Loan PB. The influence of the duration of control stimulation on the onset and recovery of neuromuscular block. Anesth Analg 1995; 80: 364–7.[Abstract]

22 Savarese JJ, Caldwell JE, Lien CA, Miller RD. Pharmacology of muscle relaxants and their antagonists. Miller RD (Ed.). Anesthesia, 5th ed. Philadelphia: Churchill Livingstone; 2000: 471–2.

23 Saitoh Y, Kaneda K, Toyooka H, Amaha K. Post-tetanic count and single twitch height at the onset of reflex movement after administration of vecuronium under different types of anaesthesia. Br J Anaesth 1994; 72: 688–90.[Abstract/Free Full Text]

24 Lowry DW, Mirakhur RK, McCarthy GJ, Carroll MT, McCourt KC. Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia. Anesth Analg 1998; 87: 936–40.[Abstract/Free Full Text]

25 Wulf H, Kahl M, Ledowski T. Augmentation of the neuromuscular blocking effects of cisatracurium during desflurane, sevoflurane, isoflurane or total i.v. anaesthesia. Br J Anaesth 1998; 80: 308–12.[Abstract/Free Full Text]

26 Kopman AF. The relationship of evoked electromyographic and mechanical responses following atracurium in humans. Anesthesiology 1985; 63: 208–11.[Medline]

27 Motulski H. Choosing an Appropriate Sample Size. Institutive Biostatistics, 1st ed. New York: Oxford University Press; 1995: 195–204.




This article has been cited by other articles:


Home page
 Canadian J. AnesthesiaHome page
Y. Saitoh
Recovery from vecuronium is delayed in patients with hypercholesterolemia: [La recuperation d'un bloc au vecuronium est retardee en cas d'hypercholesterolemie].
Can J Anesth, June 1, 2006; 53(6): 556 - 561.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Résumé de cet Article
Right arrow Full Text (PDF)
Right arrow Submit a scholarly reply
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Saitoh, Y.
Right arrow Articles by Murakawa, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saitoh, Y.
Right arrow Articles by Murakawa, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS