Comparative clinical evaluation of chandonium iodide and pancuronium bromide as muscle relaxant.
Chandonium iodide, a synthetic non-depolarising neuromuscular blocking agent and pancuronium bromide were clinically compared as muscle relaxants in 62 patients undergoing elective surgery. Anaesthesia was induced by thiopentone sodium and maintained by oxygen and nitrous oxide. Assessment of efficacy of both the muscle relaxants was graded taking into consideration intubating condition and muscular relaxation during surgery. Tolerability was assessed by noting the changes in heart rate, blood pressure and biochemical estimations. Efficacy of chandonium iodide in the dose of 0.15 to 0.18 mg/kg was comparable to that of 0.08 to 0.1 mg/kg of pancuronium bromide. Both the drugs were well tolerated.
Introduction of muscle relaxants in clinical anaesthesiology has revolutionised this branch of science and at the same time made its application in surgical practice safe. Pancuronium bromide, a bis-quaternary aminosteroid was first synthesised in 1964 and was subsequently shown to produce a non-depolarising type of neuromuscular block in animals and man. Clinical studies have shown that it is approximately 5 times as potent as dtubocurarine, with minimal cardiovascular, histamine releasing and hormonal actions. It is one of the commonly used muscle relaxants in anaesthesia practice.
Chandonium iodode (17?-methyl-3 ?-pyrrolodino-17 a-aza-D-homoandrost-5-ene dimethiodide) is a synthetic quaternary steroid 2 having neuromuscular blocking activity. In an early clinical study it was found to be an effective and well-tolerated neuromuscular blocking agent. This drug was supplied to us by Central Drug Research Institute, Lucknow, in the form of 2 ml ampoules containing 2 mg/ml of chandonium iodide.
We report here the comparative clinical evaluation of pancuronium bromide (PB) and chandonium iodide as (CI) muscle relaxants in patients undergoing elective surgery.
The study was carried out in 62 patients undergoing elective surgery. The patients received either pancuronium bromide or chandonium iodide as the sole muscle relaxant. These patients belonged to ASA grade I or II and age range of 18-60 years. An informed written consent was obtained from the patients. There were 25 males and 6 females in pancuronium group and 29 males and 2 females in chandonium iodide group. The patients were allocated to the 2 groups as per randomisation. Basal clinical examination and biochemical investigations were carried out in all the patients.
All the subjects received injection atropine sulphate (0.6 mg) intramuscularly as pre-medication 30 minutes before surgery. Anaesthesia was induced by injection of thiopentone sodium (5 mg/kg body weight) following which the muscle relaxant was injected. Patients were ventilated with 3 litres/min of oxygen and 5 litres/min nitrous oxide. Only after they were clinically judged to be relaxed enough for intubation, they were intubated. Clinical criteria used were as follows: generalised loss of muscle tone, jaw relaxation, laryngoscopy result, condition of glottic aperture response to intra-tracheal topical anaesthesia spray and muscles tone. Patients were given 5-6 blasts of 100% oxygen before intubation. Time interval between induction and intubation was noted. Condition for intubation was graded as good when glottic aperture was completely relaxed and vocal cord movements were absent during intubation; fair when minimal movements of vocal cords were present during intubation and poor when intubation was difficult due to voval cord movements.
When the conditions for intubation were graded as poor, additional doses of respective muscle relaxants were injected till it was possible to intubate.
After intubation, anaesthesia was maintained with 1.5 litre/min oxygen and 2.5 litre/min nitrous oxide. All patients received intravenous diazepam in the dose of 0.2 mg/kg body weight throughout the duration of anaesthesia. Pulse and blood pressure (B.P.) were recorded every 5 minutes. Incidence and degree of muscular movements, skin reactions like rash and erythema, excessive sweating and salivation after injection of muscle relaxant were noted.
At the end of surgery 1 mg of atropine sulphate and 2.5 mg neostigmine were used for reversal of neuromuscular blockade. After reversal, the mental status, muscular tone (ability to open eyes, open mouth, lift limbs and head on verbal command), respiration and the ability to cough were recorded. Post-operative follow-up for 24 hours was done to note any adverse effects. Blood samples were collected before and after operation for the estimation of SGOT, SGPT, total and direct bilirubin, total proteins, albumin and globulin.
The initial dose of chandonium iodide ranged between 0.15 and 0.18 mg/kg and pancuronium was used in the dose range of 0.08 to 0.1 mg/kg. The results of intubating conditions for both chandonium iodide and pancuronium bromide are given in [Table - 1] and [Table - 2] respectively.
The mean time interval for intubation was found to be 95 sec. with a maximum of 120 seconds, in patients who received pancuronium bromide while it was 3 min. and 3.5 min. respectively, in patients receiving chandonium iodide. There was no statistically significant difference in onset and duration of anaesthesia between chandonium and pancuronium.
Changes in pulse rate were noted with both muscle relaxants and are given in [Table - 3].
The mean of the pulse rate at 10, 15, 20 and 25 min. was compared with the basal value in each patient to note the percentage rise or fall. The results are given in [Table - 4]. Pancuronium bromide and chandonium iodide produced rise in pulse rate in 26 and 27 patients respectively.
The changes in systolic B.P. noted with both muscle relaxants are given in [Table - 5].
The mean of systolic B.P. at 10, 15, 20 and 25 min was compared with the basal value in each patient to note the percentage rise or fall; the results are given in Table 6.
Pancuronium bromide produced rise in systolic B.P. in 27 patients while chandonium iodide produced this effect in 16 patients while fall in systolic B.P. was observed in 15 patients of CI group and 3 patients of PB group respectively.
Basal liver function test results were compared with post-operative results. Paired 't' test was used for statistical analysis. Significant changes were noted only in total proteins (p < 0.05).
Chandonium iodide group showed a significant increase in direct bilirubin (p < 0.05) but there was no change in total bilirubin.
Skin rash, erythema or excessive sweating were not observed in any patient of either group. Patients of chandonium iodide group had severe cough immediately following reversal of neuromuscular blockade. Suction was carried out to rule out mucus plug. Nausea was present in 5 patients of PB group and in 4 patients of CI group.
This is an open randomised trial, with 31 patients in each of the 2 groups. Pre-medication was standardised and consisted of 0.6 mg of atropine sulphate intravenously 30 min before surgery. Anaesthesia was induced with intravenous injection of thiopentone sodium and in all patients the muscle relaxant under study was the sole agent used to achieve muscle relaxation for intubation and surgery.
Pancuronium bromide at a dose of 0.1 mg/kg provided conditions in 94.5% of cases Dobkin et a1  also had a similar finding achieving good relaxation in 94% of cases. Chandonium, iodide at 0.17 and 0.18 mg/kg may provide good intubating conditions, comparable to pancuronium bromide at 0.09 and 0.1 mg/kg dose.
Suri and Daljitarn Singh have recommended doses of 0.1 to 0.2 mg/kg of chandonium iodide. In the present study, response to 0.15 and 0.18 mg/kg dose had a difference of almost 100%. Hence, the effective dose range appears to be narrow. Gupta et a1 evaluated chandonium iodide in 40 patients. The onset of neuromuscular blockade was rapid and short-lasting producing good response in 31, satisfactory in 6 and poor response in 3 patients.
The time interval for intubation range 95-120 sec.) was slightly more than that reported by Bennett et a1 (range 30-90 sec.) As regards the cardiovascular effects, both PB and CI produced an increase in pulse-rate. Kelman and Kennedy 5 also observed a significant increase in heart rate following PB. Gupta et a1 in their study of 40 patients, found a mild tachycardia (6-20/min) in a few patients. In experimental study, using nonatropinised cats, CI has been shown to produce mild tachycardia in neuromuscular blocking doses. The rise in pulse rate following PB is mainly due to its atropine like action.
PB also produced a rise in B.P. Cardiovascular effects of P.B. like rise in pulse rate and B.P. have been variably attributed to blockade of vagus and sympathomimetic effect . As compared to PB, the percentage rise in BP was less in the CI group. An increase in B.P. (648 mm of Hg) was observed by Gupta et a1 in a few patients.
Liver function tests were carried out pre-operatively and post- operatively 24 hours following surgery and anaesthesia in both the groups of patients. The changes observed were within normal limits.
Reversal of neuromuscular blockade was good in all the patients of both the groups. Adverse effects like skin rash or other signs of histamine release were not observed post-operatively in either group.
This open randomised clinical study shows that CI is an effective and well-tolerated non-depolarising neuromuscular blocking agent and its efficacy and tolerability are comparable to PB.