Effect Of Diabetes Mellitus On Mivacurium Chloride-induced Muscle Relaxation: Dose-response And Time-course Relationship

Objective: This prospective study was designed to evaluate the effect of diabetes mellitus on the dose-response and time-course relationship for muscle relaxation induced by mivacurium chloride and to provide a basis for clinical rational use of drugs in the patients with diabetes mellitus.Methods: One hundred and sixty patients of either sex, aged 20-64 yr, with BMI 20-24 kg/m2, of ASA physical statusⅠor Ⅱ, scheduled for elective breast and limb surgery under general anesthesia, were enrolled in the study. All the patients were with normal heart, pulmonary, hepatic and renal functions and neuromuscular function and without water, electrolyte, and acid-base balance disturbance, and received no preoperative drugs which affected neuromusclar transmission. Patients were divided into diabetes mellitus group(group D, n=80) and non-diabetes mellitus group(group ND, n=80), depending on whether or not type 2 diabetes mellitus was complicated. The history of diabetes mellitus was above 5 yr for the patients in group D. Each group was randomly allocated into 4 subgroups. Group D was divided into D1, D2, D3 and D4 groups. Group ND was divided into ND1, ND2, ND3 and ND4 groups. Mivacurium chloride 25, 40, 55 and 70 μg/kg were injected intravenously, respectively. After routine preoperative preparation, routine monitoring of electrocardiogram(ECG), heart rate(HR), non-invasive blood pressure(NBP) and pulse oxygen saturation(Sp O2) were carried out. The depth of anesthesia and degree of muscle relaxation were monitored, and the temperature of ispilateral skin of hand was maintained at 32.0-37.0℃. After admission to the operating room, when the life signs of patients were stable, 15 min later anesthesia was induced with iv injection of midazolam 0.05mg/kg, fentanyl 4 μg/kg, and etomidate 0.2-0.3 mg/kg. After loss of consciousness, CLMRIS-1 closed-loop muscle relaxation injection system was initiated. The electrodes were placed over the ulnar nerve on the volar side of the wrist. The distal electrode was positioned where the proxomal bending line crossed the radisal side of the flexor carpi ulnaris muscle. The proximal electrode could be placed either 3-4 cm from proximal of the distal electrode or over the ulnar never at the elbow. The transducer should be placed with its largest flat side against the thumb. The transducer cable must be fixed in such a way that no traction was applier to the transducer and that movement of the thumb was not obstructed in any way. Then the CLMRIS-1 and Seted parameters were opened. Neuromuscular function was monitored by accelerography. A train of four(TOF) stimulation(current 40-60 m A, duration 0.2-0.3ms, frequency 2Hz, interval 20s) of the ulnar nerve was used. When the patients lost consciousness, calibration was carried out. When the first twitch height(T1) was maintained at 100%, mivacurium chloride was injected over 5s. When the maximum muscle relaxation was achieved, laryngeal mask airway was inserted. The patients were endotracheally intubated and mechanically ventilated(oxygen flow rate 2L/min, VT with 8ml/kg, RR 12-16 bpm, I:E 1:2). PETCO2 was maintained at 35-45 mm Hg(1mm Hg=0.133 k Pa). Anesthesia was maintained by target-controlled infusion of propofol and remifentanil, with the target plasma concentrations of 4-6μg/ml and 3-4ng/ml, respectively, to maintain BIS values at 40-60. The following indices were recorded after administration of mivacurium chloride: maximum muscle relaxation, onset time(time from injection of mivacurium chloride to inhibition of the maximum muscle relaxation), duration(inhibition of maximum muscle relaxation time) and recovery time(time from recovery from inhibition of maximum muscle relaxation to time for T1 returned to 100%) and the total time(time from the end of injection to time for T1 returned to 100%).Results: There were no significant difference among diabetic and non-diabetic patients in gender, age, body weight, and basic vital signs(P>0.05). The ED50, ED75 and ED95(95%CI) of mivacurium chloride were 79.80 μg/kg(53.58-123.02) μg/kg, 54.08 μg/kg(37.07-82.22) μg/kg and 41.40 μg/kg(28.71-62.09) μg/kg, respectively, in diabetes mellitus group, and were 87.49 μg/kg(62.80-125.31) μg/kg, 59.57 μg/kg(43.45-83.75) μg/kg and 45.60 μg/kg(33.65-63.53) μg/kg, respectively, in non-diabetes mellitus group. The ED50, ED75 and ED95 of mivacurium chloride decreased by 8.8%, 9.2% and 9.2% in diabetes mellitus group compared with non-diabetes mellitus group(P<0.05). The onset time and recovery time of mivacurium chloride were significantly prolonged in diabetes mellitus group compared with non-diabetes mellitus group(P<0.05).Conclusion: Diabetes mellitus can enhance the potency of mivacurium chloride-induced muscle relaxation and prolong its onset time and recovery time.