British Journal of Anaesthesia 1992; 68: 567-569
NEUROMUSCULAR BLOCKING ACTIVITY OF TUBOCURARINE IN PATIENTS WITH DIABETES MELLITUSf M. M. AT ALLAH, A. A. DAIF, M. M. A. SAIED AND Z. M. SONBUL
SUMMARY
KEY WORDS Complications: diabetes mellitus. Neuromuscular relaxants: tubocurarine.
Although neuromuscular problems are common in patients with diabetes mellitus, there are few studies on die activity of die neuromuscular junction in such patients. In isolated diaphragm muscle of diabetic mice, it was found that die acetylcholine potential amplitude was greater dian in control diaphragms [1]. In clinical studies, a delay in deep tendon reflexes of patients with diabetes mellitus has been reported [2-4]. Experimental studies have demonstrated a differential sensitivity of motor endplates to commonly used neuromuscular blocking drugs [1,5-7]: sensitivity to tubocurarine was decreased in diabetic rats, while die response to suxamedionium was increased [5]. This increased sensitivity to suxamethonium was reported later in cross-culture preparations of skeletal muscles of diabetic mice [6], and
PATIENTS AND METHODS
This was an open study, in 40 patients undergoing a variety of urological operations. We studied 25 patients suffering from type II diabetes mellitus and 15 non-diabetic patients as a control group. The diabetic patients were treated with oral hypoglycaemic agents and diese were replaced, the day before operation, by soluble insulin. Patients were excluded if diey had acidosis, hepatic or renal impairment, neuromuscular disease or familial history of hereditary neuromuscular disorders. The study was approved by die local Etiiics Committee and informed consent was obtained from all participants. Premedication comprised diazepam 0.15 mg kg"1 and butorphanol 30 ug kg"1 i.v. lOmin before anaesdiesia, which was induced with diiopentone 5 mg kg"1 and atropine 0.5 mg. Tracheal intubation was facilitated widi suxamedionium 1 mg kg"1. Anaesdiesia was maintained widi 66 % nitrous oxide in oxygen, supplemented widi butorphanol lOugkg" 1 if necessary. Neuromuscular block was achieved by tubocurarine in an initial dose of 0.25 mg kg"1 and incremental doses of 20 % of the initial dose. At die end of surgery, residual neuromuscular block was antagonized widi neostigmine in incremental doses of 0.5 mg mixed with atropine 0.2 mg, given at 5min intervals. The ulnar nerve was stimulated via two surface electrodes proximal to die wrist joint (Myotest). A rectangular stimulus of 0.2 ms duration and maxiMOHAMED M. ATALIAH, M.D. ; AHMED A. DAIF, M.SC. ; MOSTAFA M. A. SAIED, M.D. ; ZEINAB M. SONBUL, M.D. ; Urology and
Nephrology Center, Faculty of Medicine, University of Mansoura, Mansoura, Egypt. Accepted for Publication: December 23, 1991. Correspondence to M.M.A. f T h i s study was part of a thesis submitted by A. A. Daif to the University of Mansoura in partial fulfilment of an M.D. degree in anaesthesia.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
Previous clinical reports have suggested that deep tendon reflexes of diabetic patients are delayed and experimental studies have reported differential sensitivity of motor endplates to neuromuscular blocking drugs. These observations prompted us to study the neuromuscular effect of tubocurarine in 25 diabetic and 15 non-diabetic patients during urological surgery. Anaesthesia was induced with thiopentone followed by suxamethonium and maintained with nitrous oxide in oxygen and increments of butorphanol. Muscle relaxation was provided with tubocurarine in an initial dose of 0.25 mg kg~1 and increments of 20% of the initial dose. At the end of surgery, residual neuromuscular block was antagonized with increments of neostigmine 0.5 mg and atropine 0.2 mg. There was a delay in the onset of action of tubocurarine in diabetic patients. A noresponse state was obtained in some patients, and its duration correlated with post-tetanic count (PTC) in diabetic patients, and with post-tetanic twitch height percent (PTTH%) in the control group. We concluded that, in diabetic patients, the onset of action of tubocurarine was delayed compared with control patients, and the reliable predictor of the duration of the no-response time was PTC in diabetic patients and PTTH% in nondiabetic subjects.
confirmed in in vivo and in vitro preparations of diabetic mice, whilst diminished activity of tubocurarine could not be confirmed [1]. To our knowledge, diere have been no clinical studies reporting changes in die activity of neuromuscular blocking drugs in diabetic patients. This study was designed to examine die activity of tubocurarine in maturity-onset, type II diabetes mellitus patients and compared die effects widi diose in normal subjects.
BRITISH JOURNAL OF ANAESTHESIA
568
RESULTS
Patient characteristics and preoperative biochemical variables are shown in table I. The mean age, and fasting blood glucose of patients with diabetes mellitus were significantly greater than values in control patients. There was a delay in the neuromuscular blocking effect of tubocurarine in diabetic patients. This was manifested by an increase in onset of block and zero time (table II). Other variables did not display any significant change. There was a positive correlation between fasting blood glucose concentration and duration of tubocurarine blocking TABLE I. Patient characteristics and preoperative biochemical variables (mean (SD)). *Significantly different from control (P < 0.05)
Control group n
37.8 (21-60) 75.0(13.5) 91.7(16.2) 140.1 (2.9) 3.9 (0.5) 9.5 (0.5) 7.39 (0.03) 5.1 (0.3)
pH
Pco, (kPa)
25
14/11 52.3 (35-70)* 71.5(10.6) 129.4(41.4)* 140.6 (2.9) 3.9 (0.5) 9.4 (0.8) 7.38 (0.04) 5.3 (6.4)
TABLE II. Neuromuscular variables after administration of tubocurarine 0.25 mg kg'1 {mean (SD)). * Significant difference from control (P < 0.05)
Onset of relaxation (min)
Zero time (min) Duration of relaxation (min) Recovery time (min) Total dose of tubocurarine (ug kg"1 min"1) Total dose of neostigmine (ugkg-1)
Control group
Diabetic group
1.6(0.8) 1.4(0.5) 39.1 (15.7) 17.9 (8.3) 2.5 (0.9)
2.2(1.0)* 1.7(0.4)* 49.9 (25.9) 14.9 (7.3) 2.4 (0.8)
27(13)
25(11)
120 100 .5 80 o
60
Q
40 "o".
Statistical analysis Variables are displayed as mean (SD). Differences between similar variables in the two groups were analysed by Student's t test and the level of significance was taken as P < 0.05. Correlation tests were used to detect the degree of correlation between different variables in the same group. Multiple regression analysis using a computerized statistical package (SPSS/PC) was used.
15 9/6
Sex (M/F) Age (yr) Body weight (kg) Fasting blood glucose concn (mg dl~') Serum Na+ (mg dl"1) Serum K+ (mg dl"1) Serum Ca!+ (mg dl"1)
Diabetic group
20
o
50
70
90
o° o •
110 130 150 170 190 210 230 250 Blood glucose (mg dT1)
FIG. 1. Plot of fasting blood glucose concentration of diabetic ( • ) (n = 25) and non-diabetic (O) (« = 15) patients and the duration of effect of tubocurarine 0.25 mg kg"1 calculated from its injection until a twitch height of 10% of the basal value was regained.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
mum amplitude 60 mA was used. Contraction of the adductor policis brevis muscle was measured using a force-displacement transducer (TD 100, Myograph 2000, Biometer, Denmark). Immediately after induction of anaesthesia, supramaximal stimuli were applied to the ulnar nerve at a rate of 1 Hz until the twitch height was stable, indicating recovery from the effect of suxamethonium. This was considered the baseline height (100%). The pattern of stimulation was then changed to train-of-four (TOF) before administration of the initial dose of tubocurarine 0.25 mgkg" 1 . TOF stimulation was recorded every 12 s until the twitch height (first response of TOF) was steady (for five successive responses) or zero. TOF stimulation was continued at steady state every 1-min until the twitch height exceeded 10% of the baseline value, when an incremental dose of tubocurarine was given. If a no-response state (no response to single, tetanic or TOF) was reached after the initial dose of tubocurarine, tetanic stimulation (50 Hz) was applied for 5 s. This was followed by a 3-s pause and then single stimuli (1 Hz) until the pretetanic no-response state was reached. Posttetanic count and post-tetanic twitch height were recorded. TOF stimulation was continued at 1-min intervals until the first response appeared. Administration of tubocurarine was stopped towards the end of surgery and spontaneous recovery was allowed to develop to a TOF ratio of 25 %. Neostigmine in incremental doses of 0.5 mg and atropine 0.2 mg were given at 5-min intervals until the TOF ratio was 70%. The following variables were measured: onset of relaxation (time from initial injection of tubocurarine until 10% of the basal twitch height was attained); zero time (time from injection of tubocurarine until zero TOF ratio); duration of relaxation (time from initial injection of tubocurarine until a twitch height of 10% of the baseline value was regained); posttetanic count (PTC) (number of twitches after a tetanic stimulation of 50 Hz for 5 s, and elicited by stimuli at a frequency of 1 Hz before it reached the pretetanic no-response state again); post-tetanic twitch height percent (PTTH%) (percent of the height of the first post-tetanic twitch to the height of the basal twitch); recovery time (time for recovery of TOF ratio from 25% to 70%); no response time (NRT) (time from tetanic stimulation to first response to TOF stimulation); total dose of tubocurarine (doses of tubocurarine divided by body weight and total duration of relaxation); total dose of neostigmine (sum of the incremental doses of neostigmine used to induce recovery from 25% to 70 % TOF ratio divided by body weight).
DIABETES MELLITUS AND TUBOCURARINE
569
TABLE III. Correlation coefficient (r) and multiple regression (t) analysis of the no-response time (NRT) against posttetanic count (PTC), and post-tetanic twitch height percent (PTTH%) in patients with diabetes mellitus and a control group. * Significantly different from control (P < 0.05) PTC (number)
Control group r t
Diabetic group r t
1 1 o 1 1o
Median
NRT (mean (SD))
Range 18
PTTH% (mean (SD))
16.6(13.3) -0.211 -0.222
33.5(21.5) -0.897 -4.778
25
26.6(19.6)
25.2(18.1) -0.548* -2.270*
correlated with PTC in diabetic patients and with PTTH % in the control group. Our study suggests that diabetes mellitus reverses the normal relative reactivity of prejunctional and postjunctional cholinoceptors to tubocurarine. ACKNOWLEDGEMENT We are grateful to Professor Elmahdy M. El Bassousy, Department of Paediatrics, University of Mansoura, for help with statistical analysis.
REFERENCES
DISCUSSION
There is considerable variation in the rate of onset of neuromuscular blocking effect of tubocurarine in patients with type II diabetes mellitus. Thickening of the basement membrane of blood capillaries results from deposition of glycoproteins [8] and is present in all tissues including skeletal muscles [9]: this may contribute to this delayed effect. The blood capillary membrane of patients with diabetes mellitus has been found to be less permeable to urea [10]. The mean age of the patients with diabetes mellitus in this study was greater than that of the control group. However, the reported delay in the Tendo-Achilles reflex in diabetes mellitus was not found to correlate with age in another study [3]. There was no significant difference in the dose of tubocurarine administered in the two groups. The reported decrease in sensitivity to tubocurarine in diabetic rats [5] was not confirmed in experimental studies [1, 6]. Previous investigators [11] have attributed tetanic fade to prejunctional cholinoceptor activity, and changes in peak tetanic tension to postjunctional cholinoceptors. In our study, PTC mimics tetanic fade and may represent prejunctional cholinoceptor activity, whilst PTTH% represents peak tetanic tension and may represent postjunctional cholinoceptor activity. During the no-response state, NRT
6.
7. 8. 9.
10
11
Kimura M, Kimura I, Nojima H, Muroi M. Diabetes mellitus-induced hypersensitiviry of mouse skeletal muscles to acetylcholine and succinylcholine. Japanese Journal of Pharmacology 1986; 40: 251-256. Ismail AA, Hafiez AA, Sayed SN, Abbas EZ, Halawa FA, Youssef MM. The effect of control diabetes mellitus on plasma T 4 ) T 3 , rT, levels and half muscle relaxation period. Arab Journal of Laboratory Medicine 1983; 9: 43-53. Beardwood DM, Schumacher LR. Delay of the achilles reflex in diabetes mellitus. American Journal of the Medical Sciences 1964; 247: 324-327. Khalaf F, Habib, Ramzy MF, Bebawi E, Ismail A, ElShcemy N. The effect of triiodothyronine administration on the speed of muscle relaxation in diabetes mellitus. Journal of the Egyptian Medical Association 1984; 67: 131-137. Minker E, Kac P, Blazso G, Koltai M. A study of the origin of altered pharmacological reactivity of synapnc structures caused by diabetes and pretreatment with contrainsulin agents. Ada Phystologica Hungarica 1984; 63: 175-183. Kimura M, Fujihara M, Nojima H, Kimura I. Hypersensitivity of acetylcholine receptor in diabetic skeletal muscle to neuromuscular blockers: The effect of myotubes cultured with spinal cord or its extract. Journal of Pharmacobiodynamics 1986; 9: 29-38. Minker E, Kac P, Koltai M. Effect of muscle relaxants on the motor endplate of diabetic and glucocorticoid pretreated rats. Ada Physiologica Hungarica 1986; 67: 257-266. Spiro RG. Biochemistry of the renal glomerular basement membrane and its alterations in diabetes mellitus. New England Journal of Medicine 1973; 288: 1337-1342. Feling P. The endocrine pancreas: Diabetes mellitus. In: Feling P, Baxter JD, Broadus AE, Forhman LA, eds. Endocrinology and Metabolism. New York: McGraw-Hill Book Company, 1981; 761-868. Ismail AA, Badrawy H, Awadain MR, El-Deeb A, ElKhodary M. The rate of diffusion of urea to the C.S.F. in diabetics. Journal of The Egyptian Medical Association 1978; 61: 659-665. Stance A, Baker T. Prejunctional and postjunctional effects of tubocurarine and pancuronium in man. British Journal of Anaesthesia 1984; 56: 607-611.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
effect in diabetic patients (r = +0.506, critical value ±0.395). This was not present in the control group (fig. 1). In patients who demonstrated the no-response state following the administration of the initial dose of tubocurarine (table III) NRT correlated negatively (r = -0.548, critical value ±0.531) with PTC in patients with diabetes mellitus, and with FTTH % (r = —0.897, critical value ±0.664) in the control group. Multiple regression analysis using the variables PTC and PTTH %, and time as a dependable variable, revealed a significant relationship with PTTH% (t= -4.778, P = 0.003) in the control group, and with PTC (t = -2.270, P = 0.04) in diabetes patients.
-0.296* -0.120*
NEUROMUSCULAR BLOCKING ACTIVITY OF TUBOCURARINE IN PATIENTS WITH DIABETES MELLITUSf M. M. AT ALLAH, A. A. DAIF, M. M. A. SAIED AND Z. M. SONBUL
SUMMARY
KEY WORDS Complications: diabetes mellitus. Neuromuscular relaxants: tubocurarine.
Although neuromuscular problems are common in patients with diabetes mellitus, there are few studies on die activity of die neuromuscular junction in such patients. In isolated diaphragm muscle of diabetic mice, it was found that die acetylcholine potential amplitude was greater dian in control diaphragms [1]. In clinical studies, a delay in deep tendon reflexes of patients with diabetes mellitus has been reported [2-4]. Experimental studies have demonstrated a differential sensitivity of motor endplates to commonly used neuromuscular blocking drugs [1,5-7]: sensitivity to tubocurarine was decreased in diabetic rats, while die response to suxamedionium was increased [5]. This increased sensitivity to suxamethonium was reported later in cross-culture preparations of skeletal muscles of diabetic mice [6], and
PATIENTS AND METHODS
This was an open study, in 40 patients undergoing a variety of urological operations. We studied 25 patients suffering from type II diabetes mellitus and 15 non-diabetic patients as a control group. The diabetic patients were treated with oral hypoglycaemic agents and diese were replaced, the day before operation, by soluble insulin. Patients were excluded if diey had acidosis, hepatic or renal impairment, neuromuscular disease or familial history of hereditary neuromuscular disorders. The study was approved by die local Etiiics Committee and informed consent was obtained from all participants. Premedication comprised diazepam 0.15 mg kg"1 and butorphanol 30 ug kg"1 i.v. lOmin before anaesdiesia, which was induced with diiopentone 5 mg kg"1 and atropine 0.5 mg. Tracheal intubation was facilitated widi suxamedionium 1 mg kg"1. Anaesdiesia was maintained widi 66 % nitrous oxide in oxygen, supplemented widi butorphanol lOugkg" 1 if necessary. Neuromuscular block was achieved by tubocurarine in an initial dose of 0.25 mg kg"1 and incremental doses of 20 % of the initial dose. At die end of surgery, residual neuromuscular block was antagonized widi neostigmine in incremental doses of 0.5 mg mixed with atropine 0.2 mg, given at 5min intervals. The ulnar nerve was stimulated via two surface electrodes proximal to die wrist joint (Myotest). A rectangular stimulus of 0.2 ms duration and maxiMOHAMED M. ATALIAH, M.D. ; AHMED A. DAIF, M.SC. ; MOSTAFA M. A. SAIED, M.D. ; ZEINAB M. SONBUL, M.D. ; Urology and
Nephrology Center, Faculty of Medicine, University of Mansoura, Mansoura, Egypt. Accepted for Publication: December 23, 1991. Correspondence to M.M.A. f T h i s study was part of a thesis submitted by A. A. Daif to the University of Mansoura in partial fulfilment of an M.D. degree in anaesthesia.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
Previous clinical reports have suggested that deep tendon reflexes of diabetic patients are delayed and experimental studies have reported differential sensitivity of motor endplates to neuromuscular blocking drugs. These observations prompted us to study the neuromuscular effect of tubocurarine in 25 diabetic and 15 non-diabetic patients during urological surgery. Anaesthesia was induced with thiopentone followed by suxamethonium and maintained with nitrous oxide in oxygen and increments of butorphanol. Muscle relaxation was provided with tubocurarine in an initial dose of 0.25 mg kg~1 and increments of 20% of the initial dose. At the end of surgery, residual neuromuscular block was antagonized with increments of neostigmine 0.5 mg and atropine 0.2 mg. There was a delay in the onset of action of tubocurarine in diabetic patients. A noresponse state was obtained in some patients, and its duration correlated with post-tetanic count (PTC) in diabetic patients, and with post-tetanic twitch height percent (PTTH%) in the control group. We concluded that, in diabetic patients, the onset of action of tubocurarine was delayed compared with control patients, and the reliable predictor of the duration of the no-response time was PTC in diabetic patients and PTTH% in nondiabetic subjects.
confirmed in in vivo and in vitro preparations of diabetic mice, whilst diminished activity of tubocurarine could not be confirmed [1]. To our knowledge, diere have been no clinical studies reporting changes in die activity of neuromuscular blocking drugs in diabetic patients. This study was designed to examine die activity of tubocurarine in maturity-onset, type II diabetes mellitus patients and compared die effects widi diose in normal subjects.
BRITISH JOURNAL OF ANAESTHESIA
568
RESULTS
Patient characteristics and preoperative biochemical variables are shown in table I. The mean age, and fasting blood glucose of patients with diabetes mellitus were significantly greater than values in control patients. There was a delay in the neuromuscular blocking effect of tubocurarine in diabetic patients. This was manifested by an increase in onset of block and zero time (table II). Other variables did not display any significant change. There was a positive correlation between fasting blood glucose concentration and duration of tubocurarine blocking TABLE I. Patient characteristics and preoperative biochemical variables (mean (SD)). *Significantly different from control (P < 0.05)
Control group n
37.8 (21-60) 75.0(13.5) 91.7(16.2) 140.1 (2.9) 3.9 (0.5) 9.5 (0.5) 7.39 (0.03) 5.1 (0.3)
pH
Pco, (kPa)
25
14/11 52.3 (35-70)* 71.5(10.6) 129.4(41.4)* 140.6 (2.9) 3.9 (0.5) 9.4 (0.8) 7.38 (0.04) 5.3 (6.4)
TABLE II. Neuromuscular variables after administration of tubocurarine 0.25 mg kg'1 {mean (SD)). * Significant difference from control (P < 0.05)
Onset of relaxation (min)
Zero time (min) Duration of relaxation (min) Recovery time (min) Total dose of tubocurarine (ug kg"1 min"1) Total dose of neostigmine (ugkg-1)
Control group
Diabetic group
1.6(0.8) 1.4(0.5) 39.1 (15.7) 17.9 (8.3) 2.5 (0.9)
2.2(1.0)* 1.7(0.4)* 49.9 (25.9) 14.9 (7.3) 2.4 (0.8)
27(13)
25(11)
120 100 .5 80 o
60
Q
40 "o".
Statistical analysis Variables are displayed as mean (SD). Differences between similar variables in the two groups were analysed by Student's t test and the level of significance was taken as P < 0.05. Correlation tests were used to detect the degree of correlation between different variables in the same group. Multiple regression analysis using a computerized statistical package (SPSS/PC) was used.
15 9/6
Sex (M/F) Age (yr) Body weight (kg) Fasting blood glucose concn (mg dl~') Serum Na+ (mg dl"1) Serum K+ (mg dl"1) Serum Ca!+ (mg dl"1)
Diabetic group
20
o
50
70
90
o° o •
110 130 150 170 190 210 230 250 Blood glucose (mg dT1)
FIG. 1. Plot of fasting blood glucose concentration of diabetic ( • ) (n = 25) and non-diabetic (O) (« = 15) patients and the duration of effect of tubocurarine 0.25 mg kg"1 calculated from its injection until a twitch height of 10% of the basal value was regained.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
mum amplitude 60 mA was used. Contraction of the adductor policis brevis muscle was measured using a force-displacement transducer (TD 100, Myograph 2000, Biometer, Denmark). Immediately after induction of anaesthesia, supramaximal stimuli were applied to the ulnar nerve at a rate of 1 Hz until the twitch height was stable, indicating recovery from the effect of suxamethonium. This was considered the baseline height (100%). The pattern of stimulation was then changed to train-of-four (TOF) before administration of the initial dose of tubocurarine 0.25 mgkg" 1 . TOF stimulation was recorded every 12 s until the twitch height (first response of TOF) was steady (for five successive responses) or zero. TOF stimulation was continued at steady state every 1-min until the twitch height exceeded 10% of the baseline value, when an incremental dose of tubocurarine was given. If a no-response state (no response to single, tetanic or TOF) was reached after the initial dose of tubocurarine, tetanic stimulation (50 Hz) was applied for 5 s. This was followed by a 3-s pause and then single stimuli (1 Hz) until the pretetanic no-response state was reached. Posttetanic count and post-tetanic twitch height were recorded. TOF stimulation was continued at 1-min intervals until the first response appeared. Administration of tubocurarine was stopped towards the end of surgery and spontaneous recovery was allowed to develop to a TOF ratio of 25 %. Neostigmine in incremental doses of 0.5 mg and atropine 0.2 mg were given at 5-min intervals until the TOF ratio was 70%. The following variables were measured: onset of relaxation (time from initial injection of tubocurarine until 10% of the basal twitch height was attained); zero time (time from injection of tubocurarine until zero TOF ratio); duration of relaxation (time from initial injection of tubocurarine until a twitch height of 10% of the baseline value was regained); posttetanic count (PTC) (number of twitches after a tetanic stimulation of 50 Hz for 5 s, and elicited by stimuli at a frequency of 1 Hz before it reached the pretetanic no-response state again); post-tetanic twitch height percent (PTTH%) (percent of the height of the first post-tetanic twitch to the height of the basal twitch); recovery time (time for recovery of TOF ratio from 25% to 70%); no response time (NRT) (time from tetanic stimulation to first response to TOF stimulation); total dose of tubocurarine (doses of tubocurarine divided by body weight and total duration of relaxation); total dose of neostigmine (sum of the incremental doses of neostigmine used to induce recovery from 25% to 70 % TOF ratio divided by body weight).
DIABETES MELLITUS AND TUBOCURARINE
569
TABLE III. Correlation coefficient (r) and multiple regression (t) analysis of the no-response time (NRT) against posttetanic count (PTC), and post-tetanic twitch height percent (PTTH%) in patients with diabetes mellitus and a control group. * Significantly different from control (P < 0.05) PTC (number)
Control group r t
Diabetic group r t
1 1 o 1 1o
Median
NRT (mean (SD))
Range 18
PTTH% (mean (SD))
16.6(13.3) -0.211 -0.222
33.5(21.5) -0.897 -4.778
25
26.6(19.6)
25.2(18.1) -0.548* -2.270*
correlated with PTC in diabetic patients and with PTTH % in the control group. Our study suggests that diabetes mellitus reverses the normal relative reactivity of prejunctional and postjunctional cholinoceptors to tubocurarine. ACKNOWLEDGEMENT We are grateful to Professor Elmahdy M. El Bassousy, Department of Paediatrics, University of Mansoura, for help with statistical analysis.
REFERENCES
DISCUSSION
There is considerable variation in the rate of onset of neuromuscular blocking effect of tubocurarine in patients with type II diabetes mellitus. Thickening of the basement membrane of blood capillaries results from deposition of glycoproteins [8] and is present in all tissues including skeletal muscles [9]: this may contribute to this delayed effect. The blood capillary membrane of patients with diabetes mellitus has been found to be less permeable to urea [10]. The mean age of the patients with diabetes mellitus in this study was greater than that of the control group. However, the reported delay in the Tendo-Achilles reflex in diabetes mellitus was not found to correlate with age in another study [3]. There was no significant difference in the dose of tubocurarine administered in the two groups. The reported decrease in sensitivity to tubocurarine in diabetic rats [5] was not confirmed in experimental studies [1, 6]. Previous investigators [11] have attributed tetanic fade to prejunctional cholinoceptor activity, and changes in peak tetanic tension to postjunctional cholinoceptors. In our study, PTC mimics tetanic fade and may represent prejunctional cholinoceptor activity, whilst PTTH% represents peak tetanic tension and may represent postjunctional cholinoceptor activity. During the no-response state, NRT
6.
7. 8. 9.
10
11
Kimura M, Kimura I, Nojima H, Muroi M. Diabetes mellitus-induced hypersensitiviry of mouse skeletal muscles to acetylcholine and succinylcholine. Japanese Journal of Pharmacology 1986; 40: 251-256. Ismail AA, Hafiez AA, Sayed SN, Abbas EZ, Halawa FA, Youssef MM. The effect of control diabetes mellitus on plasma T 4 ) T 3 , rT, levels and half muscle relaxation period. Arab Journal of Laboratory Medicine 1983; 9: 43-53. Beardwood DM, Schumacher LR. Delay of the achilles reflex in diabetes mellitus. American Journal of the Medical Sciences 1964; 247: 324-327. Khalaf F, Habib, Ramzy MF, Bebawi E, Ismail A, ElShcemy N. The effect of triiodothyronine administration on the speed of muscle relaxation in diabetes mellitus. Journal of the Egyptian Medical Association 1984; 67: 131-137. Minker E, Kac P, Blazso G, Koltai M. A study of the origin of altered pharmacological reactivity of synapnc structures caused by diabetes and pretreatment with contrainsulin agents. Ada Phystologica Hungarica 1984; 63: 175-183. Kimura M, Fujihara M, Nojima H, Kimura I. Hypersensitivity of acetylcholine receptor in diabetic skeletal muscle to neuromuscular blockers: The effect of myotubes cultured with spinal cord or its extract. Journal of Pharmacobiodynamics 1986; 9: 29-38. Minker E, Kac P, Koltai M. Effect of muscle relaxants on the motor endplate of diabetic and glucocorticoid pretreated rats. Ada Physiologica Hungarica 1986; 67: 257-266. Spiro RG. Biochemistry of the renal glomerular basement membrane and its alterations in diabetes mellitus. New England Journal of Medicine 1973; 288: 1337-1342. Feling P. The endocrine pancreas: Diabetes mellitus. In: Feling P, Baxter JD, Broadus AE, Forhman LA, eds. Endocrinology and Metabolism. New York: McGraw-Hill Book Company, 1981; 761-868. Ismail AA, Badrawy H, Awadain MR, El-Deeb A, ElKhodary M. The rate of diffusion of urea to the C.S.F. in diabetics. Journal of The Egyptian Medical Association 1978; 61: 659-665. Stance A, Baker T. Prejunctional and postjunctional effects of tubocurarine and pancuronium in man. British Journal of Anaesthesia 1984; 56: 607-611.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
effect in diabetic patients (r = +0.506, critical value ±0.395). This was not present in the control group (fig. 1). In patients who demonstrated the no-response state following the administration of the initial dose of tubocurarine (table III) NRT correlated negatively (r = -0.548, critical value ±0.531) with PTC in patients with diabetes mellitus, and with FTTH % (r = —0.897, critical value ±0.664) in the control group. Multiple regression analysis using the variables PTC and PTTH %, and time as a dependable variable, revealed a significant relationship with PTTH% (t= -4.778, P = 0.003) in the control group, and with PTC (t = -2.270, P = 0.04) in diabetes patients.
-0.296* -0.120*
