Biomedical subjects
Publications and source records attributed to J Engbaek.
Four case histories are presented illustrating the unpleasant and serious reactions that may follow precurarization with small doses of non-depolarizing muscle relaxants. The importance of preoperative information, the necessity of relating the dose of the precurarizing drug to the weight of the patient and the possibility of hypersensitivity to this drug are emphasized.
Twenty cases of severe bradycardia, including 12 cases of cardiac asystole, following administration of a single dose of suxamethonium to 17 adult patients are presented. Treatment consisted of i.v. atropine in 16 cases, and in four cases external cardiac massage or a precordial thump was also given. Remission was complete in all cases. The mechanism is not known, but it is suggested that i.v. administration of fentanyl at induction may enhance the tendency to bradycardia following suxamethonium. Absence of preoperative atropine may also be of importance.
The haemodynamic effects of vecuronium and pancuronium were studied in 20 healthy patients during diazepam/ketamine anaesthesia. Anaesthesia was induced with glycopyrrolate 3 micrograms/kg, diazepam 0.3 mg/kg and ketamine 1.0 mg/kg as a bolus and 1.0 mg/kg over 10 min. After induction, anaesthesia was maintained with ketamine infusion 1.0 mg/kg/h. The lungs were ventilated with 50% nitrous oxide in oxygen. Equipotent doses of vecuronium (74 micrograms/kg) or pancuronium (99 micrograms/kg) were administered for intubation. The thoracic impedance, ECG and phonocardiogram were recorded during the induction of anaesthesia. The results suggest that vecuronium has no cardiovascular effects during ketamine anaesthesia, whereas pancuronium due to its chronotropic effect, causes a deterioration in left ventricular performance.
The neuromuscular blocking properties of vecuronium (Org NC 45) and pancuronium were compared in 40 patients during halothane anaesthesia. Onset time was found to be dose-dependent, but no significant difference was found between the two drugs. The duration of action of vecuronium was significantly shorter than pancuronium. Times to 90% recovery of twitch height following vecuronium 0.03 mg kg-1 and 0.057 mg kg-1 were 32.0 min and 44.9 min, respectively, compared with 72.9 min and 124.7 min following equipotent doses of pancuronium (0.042 mg kg-1 and 0.08 mg kg-1). Recovery indices following both doses of vecuronium (10.0 min and 11.8 min) were significantly shorter than after pancuronium (31.0 min and 46.9 min). The reversal times of vecuronium (times from 10% to 90% twitch height recovery) were significantly shorter than those of pancuronium (7.9 min and 7.3 min, respectively, compared with 17.1 min and 17.7 min).
The cardiac effects of equipotent doses of pancuronium and vecuronium (Org NC 45) were compared in 20 patients, anaesthetized with halothane. Heart rate and arterial pressure were recorded and the systolic time intervals were evaluated from simultaneous tracings of ECG, phonocardiogram and carotid pulse curve. Pancuronium 0.08 mg kg-1 caused a significant increase in heart rate (20%), insignificant changes in arterial pressure and significant changes in systolic time intervals compatible with a minor positive inotropic action. The equipotent dose of vecuronium (0.057 mg kg-1) caused no significant changes in heart rate, arterial pressure or systolic time intervals.
Induction of anaesthesia may pose a significant hazard to patients with critical cardiovascular status. Ketamine has been advocated as the drug of choice for maintaining cardiovascular performance during induction of anaesthesia in severely ill surgical patients. The purpose of this study was to compare the relative changes in the haemodynamic effects of ketamine and thiopentone during the first 30 min of anaesthesia induction measured by thoracic impedance cardiography. Twelve adult high-risk surgical patients, ASA class III-V, were induced with thiopentone and fentanyl or with infusion of ketamine. Cardiac output decreased to 69% in the thiopentone group (P less than 0.05), but was hardly affected in the ketamine group. The pre-ejection period to left ventricular time (PEPI) and the pre-ejection period index ratio increased significantly after thiopentone (P less than 0.05), while ketamine caused only minimal changes in left ventricular performance. The diastolic pressure time index to systolic pressure time index ration decreased significantly in both groups.
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A double-blind study of 20 patients with ulcerative colitis during treatment with diphenoxylate 5 mg three times daily and placebo is reported. There were two treatment periods of 14 days each, with cross-over technique and randomized sequence. Test variable for constipating effect was the mean number of defaecations per day. The criterion for inclusion of patients was the presence of 4 or more daily bowel movements; 2 patients did not complete the investigation. Significant difference (p less than 0.01) in constipating effect between diphenoxylase and placebo was demonstrated both during a period of 12 days and a period of 6 days (Tables II and III). The average number of bowel movements were reduced by 0.7 and 1.3 per day respectively. Side-effects during treatment with diphenoxylate were seen in 53% (Table III) with significant difference against placebo (p less than 0.05). On the basis of the small absolute reduction of defaecation frequency side-effects, it is concluded that diphenoxylate has no place in the routine treatment of ulcerative colitis.
The adverse reactions seen following administration of neuromuscular blocking agents are mainly cardiovascular. Due to the lack of specificity for the nicotinic receptor at the neuromuscular junction, these agents may interact with receptors in autonomic ganglia and muscarinic receptors in the heart. Furthermore, muscle relaxants may have histamine-releasing properties. The cardiovascular effects vary with potency and specificity of the drug, depending mainly on the chemical structure. Pancuronium, fazadinium and especially gallamonium block cardiac muscarinic receptors, and tachycardia may be seen. Atracurium, metocurine and in particular d-tubocurarine have histamine-releasing properties and may cause flushing, hypotension and tachycardia. Vecuronium has no effect on the cardiovascular system. The effect of succinylcholine on heart rate differs between children, where bradycardia is seen, and adults in whom tachycardia may follow. However, bradycardia may occur in adults following a single dose. Succinylcholine increases plasma potassium, especially in patients with nerve damage, and arrhythmias may be observed. The neuromuscular adverse effects of succinylcholine, such as fasciculations and increased gastric and intraocular pressure, may be prevented by precurarisation. Many drugs interact with neuromuscular blocking agents and there is often a potentiation of the neuromuscular effect. This is of clinical importance in the case of antibiotics, inhalational anaesthetics, lithium and cyclosporin. Difficulty in reversing the block may occur with calcium channel blockers and polymyxin. However, some drugs, such as phenytoin, carbamazepine and lithium, may cause resistance to neuromuscular blocking agents. Furthermore, clinically important interactions exist between individual neuromuscular blocking drugs. Precurarisation with a non-depolarising drug prolongs the onset of succinylcholine, and conversely a prolonged effect of non-depolarising drugs is seen following succinylcholine. The effect of succinylcholine is markedly prolonged if the drug is administered during recovery from pancuronium blockade or following neostigmine for reversal. Succinylcholine is hydrolysed by plasma cholinesterase, and drugs which decrease the activity of this enzyme may produce a prolonged block, i.e. contraceptive pills, cyclophosphamide, echothiopate and organophosphate.