Reversal by suramin of neuromuscular block produced by pancuronium in the anaesthetized rat.

1. Rats were anaesthetized with sodium pentobarbitone and maximal twitches of a tibialis anterior muscle were evoked by stimulation of the motor nerve. 2. Suramin, injected intravenously in a series of cumulative bolus doses, each 15 mg kg-1, completely reversed a 90% depression of twitches maintained by a continuous intravenous infusion of pancuronium. The cumulated dose necessary to restore twitches to 50% of their control amplitude was 35 mg kg-1. Suramin did not modify a similar degree of block produced by suxamethonium, nor did it affect the amplitude of control maximal twitches, even in cumulative doses up to 150 mg kg-1. 3. The effects of bolus doses of suramin (85 mg kg-1), neostigmine (0.03 mg kg-1) and 4-aminopyridine (1.2 mg kg-1), calculated to restore pancuronium-blocked twitches to 95% of control amplitude, were compared. Suramin produced the most rapid reversal (1.1 +/- 0.5 min), but its duration of action was the shortest (9.4 +/- 1.6 min). Suramin was without effect on heart rate or blood pressure in the doses used. 4. The results showed that suramin reversed neuromuscular block produced by nondepolarizing blocking drug, pancuronium, but was without effect on a block produced by the depolarizing blocking drug, suxamethonium. Its short duration of action suggests that suramin would probably not be of value clinically as a reversal agent. However, it is possible that it might serve as a starter compound for the synthesis and development of a new class of reversal agents for use in anaesthetic practice.

The effect of general anesthetic agents on intraocular pressure.

General anesthetics may have diverse effects on intraocular pressure, possibly leading to serious complications such as vitreous loss and iris prolapse. Clinical and research findings on the effects of depolarizing and nondepolarizing agents are discussed, and methods of avoiding or counteracting adverse reactions are summarized.

Vecuronium: a new nondepolarizing neuromuscular-blocking agent. Clinical pharmacology, pharmacokinetics, cardiovascular effects and use in special clinical situations.

Vecuronium provides additional flexibility to the clinician using neuromuscular-blocking drugs. Its shorter duration of action, lack of significant cardiovascular effects and lack of dependence on the kidney for elimination provide clinical advantages over, or alternatives to, currently available, nondepolarizing neuromuscular-blocking drugs.

Neuromuscular relaxants in the neonate.

Neuromuscular blockade frequently is employed to facilitate mechanical ventilation and other therapeutic interventions in adults and children. In recent years it has been suggested that the use of neuromuscular blockade in the management of premature infants who are ventilated for respiratory distress will reduce the incidence of barotrauma and intracranial hemorrhage. Subsequently, neuromuscular blocking agents have become some of the most commonly used medications in the intensive care nursery. A discussion of these drugs is included in this article to improve the understanding of their pharmacology, the indications and consequence of their use, and their potential side effects. Additionally, the recent introduction of new, shorter-acting agents warrants a review of current practice.

Effect of prior administration of a non-depolarising muscle relaxant on the action of suxamethonium in the dog.

The non-depolarising muscle relaxants alcuronium (0.1 mg kg-1), gallamine (1 mg kg-1) and pancuronium (0.06 mg kg-1) were administered to six dogs. At 50 per cent return of neuromuscular activity, as measured by the train-of-four technique, the depolarising muscle relaxant suxamethonium (0.3 mg kg-1) was injected intravenously. At 50 per cent return of neuromuscular activity, atropine and neostigmine were administered to reverse the neuromuscular block. The duration of action of suxamethonium was reduced by each of the non-depolarising muscle relaxants.

Recording of train-of-four evoked muscle responses from the nose and foreleg in the intact dog.

Evoked muscle responses to train-of-four electrical nerve stimuli were recorded from the nose and foreleg in the intact dog. Low and high doses of both suxamethonium and either pancuronium or gallamine were injected, and the recordings of muscle responses from each dog were examined. Recordings taken from the foreleg showed the presence of train-of-four fade until complete neuromuscular block was established. Simultaneous recordings from the nose showed the development of a train-of-four fade in early stages of neuromuscular block, but as the block increased, an unusual response developed where the twitch height became equal. This finding occurred following suxamethonium as well as non-depolarising relaxants.

Effect of prior administration of suxamethonium on non-depolarising muscle relaxants in the dog.

The depolarising muscle relaxant suxamethonium (0.3 mg kg-1) was administered to six dogs. At 50 per cent return of the neuromuscular activity, as measured by the train-of-four technique, a non-depolarising muscle relaxant was administered. Three drugs, alcuronium (0.1 mg kg-1), gallamine (1.0 mg kg-1) and pancuronium (0.06 mg kg-1) were injected intravenously. At the 50 per cent return of neuromuscular activity, atropine and neostigmine were administered to reverse the neuromuscular block. The duration of action of the three non-depolarising relaxants was reduced by the prior administration of suxamethonium.

The value of pancuronium in prolonged intraocular operations.

We wished to determine the effectiveness of Pancuronium, a non-depolarizing muscle relaxant, in prolonged intraocular operations. We compared the variations in intraocular pressure when using four different methods of induction of general anesthesia. With Pancuronium the intraocular pressure fell initially and then rose to just below pre-induction levels and remained there. Our study suggests that pancuronium stabilizes intraocular pressure at a level which is highly desirable for intraocular surgery.

Succinylcholine and intraocular pressure.

Thirty-one patients (61 eyes) had a rise in intraocular pressure averaging 8.2 mm Hg following the use of succinylcholine as a muscle relaxant prior to general anesthesia. Just prior to the start of surgery (an average of 14 minutes following Anectine administration), the tension had returned to the control level. Ten patients (20 eyes) had pancuronium used without succinylcholine. No change in intraocular tension was noted with this agent and pressure remained unchanged at the start of surgery. Work of other investigators, using the "spring back balance" test and strain gauge force measurement to rotate the globe, indicate that the effect of Anectine upon the extraocular muscles may take 20 to 30 minutes to wear off. This is long after the return of intraocular pressure to control values and suggests that monitoring of intraocular tension may not be accurate method of assessing the action of Anectine upon the eye muscles. The mechanism of increased fluid outflow, not muscle relaxation, probably accounts for this lowering of intraocular pressure.

On mechanism of action of ethanol-induced contraction of frog rectus abdominis.

Ethanol in low doses (0.5 to 4 M) causes contraction of isolated frog rectus abdominis muscle. Higher concentration did not produce any further increase in maximum response. Pretreatment with dantrolene produced partial but equal inhibition of acetylcholine (Ach) induced as well as ethanol-induced contraction in equieffective doses. Pretreatment with pancuronium produced right and downward shift of ethanol induced contraction. Pretreatment with succinylcholine produced persistent contraction of tissue and this response remained unaffected on subsequent treatment with Ach as well as ethanol. Pretreatment with hemicholinium abolished ethanol induced contraction, although tissue remained viable as confirmed on addition of Ach. The contraction induced by ethanol decreased on pretreatment with dantrolene as well as in Ca2+ free ringer. The results indicate that ethanol induced contraction may be due to release of Ach or Ach like neurotransmitter at neuromuscular junction and calcium acts as mediator to produce these effects.

Influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission.

The influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission was studied in the isolated saphenous vein of the dog. Pancuronium increased the response of vascular smooth muscle to adrenergic nerve stimulation and to exogenous norepinephrine; gallamine, d-tubocurarine and succinylcholine had no effect. The relaxation caused by small doses of acetylcholine added during sympathetic nerve stimulation (prejunctional effect), was inhibited by pancuronium and by gallamine. In vein strips, charged with (3H) norepinephrine, acetylcholine inhibits the catecholamine-efflux evoked by sympathetic nerve stimulation. That inhibition was abolished by gallamine. This confirms that gallamine inhibits the prejunctional effect of acetylcholine on adrenergic neurotransmission. When extrapolated to the intact organism, this means that gallamine and pancuronium will augment the release of norepinephrine by acting as muscarinic antagonists also at prejunctional receptor sites in tissues exposed to combined sympathetic and vagal nerve activity. This mechanism would explain in part the cardiovascular effects of these muscle relaxants.

[Role of vecuronium in comparison with curariform drugs used in man]. / Place du vécuronium par rapport aux curares utilisés en clinique humaine.

Vecuronium, a new non-depolarizing muscle relaxant, was more powerful than d-tubocurarine, gallamine and alcuronium. Its muscle blocking effect was similar to that of pancuronium. It had a smaller distribution volume and a quicker elimination half-life than the other non-depolarizing muscle blocking drugs. The time of onset and duration of action, as well as the time for recovery were also shorter, being 3-5 min, 17-22 min and 25 min respectively. The accumulation of vecuronium in the body was low; increasing the dose increases the duration of action, but not the recovery time. No adverse effect has been reported as yet. Compared with suxamethonium, a depolarizing muscle relaxant, it had a longer time of onset and duration of action. Vecuronium cannot therefore replace suxamethonium for endotracheal intubation.

[Clinical use of vecuronium during celioscopy]. / Utilisation clinique du vécuronium au cours des coelioscopies.

In order to determine if vecuronium can be used for short operations, 40 women were studied during laparoscopy, randomly assigned to four groups: suxamethonium 1 mg X kg-1 in a single bolus followed by an infusion (group A), vecuronium 0.05 mg X kg-1 (group B), vecuronium 0.06 mg X kg-1 (group C) and vecuronium 0.07 mg X kg-1 (group D). Mean duration of operation was 22-25 min. Tracheal intubation can be performed in good conditions in all patients in group A and D, in 5/10 in group B and in 7/10 in group C. During laparoscopy, muscular relaxation was considered excellent in all patients in group A and D, 5/10 sufficient and 5/10 excellent in group C, 5/10 insufficient and 5/10 sufficient in group B. There were 7 reinjections in group B, 2 in group C and 1 in group A. The delay between the end of the procedure and extubation was the same in group A and C (7 min). This delay was significantly higher in group D (9 min). The delay between extubation and positive head lift test was significantly higher in group D. We conclude that the time course of action of vecuronium 0.06 mg X kg-1 is that required for a pelvic laparoscopy of 22-25 min; however, the conditions of intubation are not always perfect. Intubation is easier with a 0.07 mg X kg-1 dose; this dose induces a slight delay for extubation and positive head lift test. In all cases, the patient must be closely watched in a recovery ward.

The effects of suxamethonium and pancuronium on the haemodynamic response to endotracheal intubation.

The pharmacological effects of suxamethonium and pancuronium on the cardiovascular system may vary and therefore alter the haemodynamic response to intubation. The arterial blood pressure, the heart rate and the rate pressure product were measured as parameters of haemodynamic change in forty adult ASA. I and II patients undergoing laryngoscopy and endotracheal intubation in a randomised controlled study. The patients were induced with either thiopentone/suxamethonium (Group A) or thiopentone/pancuronium (Group B). There was no significant difference between the groups on comparison of systolic and diastolic blood pressure changes. Pancuronium, however, caused a significantly higher rise in the heart rate after endotracheal intubation compared to suxamethonium. In both groups the maximum rate pressure product occurred one minute after intubation, rising by 56% in the suxamethonium group and 64% in the pancuronium group compared to control values. In conclusion, there were significant and statistically similar increases in systolic and diastolic blood pressures and rate pressure product following intubation in both groups with values significantly above baseline until three minutes post intubation but the increase in heart rate in group A was significantly less than that in group B.

[Comparative clinical study of the effects of vecuronium and suxamethonium during oto-rhino-laryngeal and tracheobronchial laser surgery]. / Etude clinique comparative des effets du vécuronium et du suxaméthonium au cours des chirurgies oto-rhino-laryngologique et trachéo-bronchique par laser.

52 patients selected at random were assigned to four groups according to the surgery and muscle relaxant used: vecuronium (group A) and suxamethonium (group B) in ENT, vecuronium (group C) and suxamethonium (group D) for laser surgery. The first dose of vecuronium was 0.05 mg X kg-1, followed by repeat doses of 0.0125 mg X kg-1; suxamethonium was first given in a dose of 1 mg X kg-1, this being followed by a drip of 3 mg X kg-1. The anaesthetic protocol was the same for all groups. The results showed a shorter onset of action with suxamethonium (group A: 210 +/- 30 s, group B: 75 +/- 15 s, group C: 200 +/- 50 s, group D: 80 +/- 20 s) and a similar duration of action for the initial doses of the two drugs (group A: 9 +/- 3 min, group B: 6 +/- 3 min, group C: 11 +/- 4 min, group D: 7 +/- 2 min). Continuing the muscle relaxation proved easier with the suxamethonium; signs of decurarization occurred rather unexpectedly with vecuronium. No adverse effect was seen with vecuronium, whilst the diastolic blood pressure rose 20% during the first 25 min following the administration of suxamethonium. It can be concluded that, in the absence of monitoring of the curarization, the repeated administration of vecuronium with a first dose of 0.05 mg X kg-1 brought few advantages compared with the continuous infusion of suxamethonium.

[The effect of succinylcholine on vecuronium and pancuronium].

In 105 adult patients under halothane anesthesia, the neuromuscular blocking effects of vecuronium and pancuronium were determined with prior succinylcholine 1 mg.kg-1 administration and without. Force of the evoked twitch increased 123.7% of control after recovery from succinylcholine-induced block. Prior administration of succinylcholine was associated with a leftward shift of dose-response curve of vecuronium or pancuronium. Onset of the force reduction from initial dose (0.08 mg.kg-1) was faster and recovery from initial and maintenance doses (0.02 mg.kg-1) were slower. This potentiating effect persisted at least 2 hours.

[Effect of cimetidine on neuromuscular blockade by succinylcholine and pancuronium].

The effect of cimetidine on neuromuscular blockade by succinylcholine and pancuronium was investigated in 54 adult patients scheduled for elective surgery. The neuromuscular blocking properties were estimated with single twitch height (T1) which was obtained by measuring the acceleration of adduction of the thumb in response to the ulnar nerve stimulation under N2O-fentanyl anesthesia. In cimetidine group, cimetidine 200 mg was administered orally on the night before surgery and 90 mins before anesthesia. Succinylcholine 1 mg.kg-1 (n = 14) or 1.5 mg.kg-1 (n = 20) was injected intravenously, and the onset time (from injection to 0% T1), the duration of maximal block (0% T1), and the recovery time from injection to 50% and 75% of control twitch height were evaluated. ED25 and ED50 of pancuronium were calculated from the dose response curve obtained by incremental administration of the drug (n = 20) whose total cumulative dose was 0.1 mg.kg-1. The recovery index of pancuronium was determined by measuring the 25%-75% recovery time. There was no significant difference between cimetidine pretreated patients and non-pretreated patients regarding these parameters of neuromuscular blockade with both succinylcholine and pancuronium. In conclusion, cimetidine has no influence on neuromuscular blockade of succinylcholine and pancuronium under N2O-fentanyl anesthesia.

[Influence of small doses of vecuronium and pancuronium on succinylcholine-induced neuromuscular blockade].

The effects of pretreatments with vecuronium (VB) and pancuronium (PB) on succinylcholine (SCC)-induced neuromuscular blockade were evaluated in 266 patients using electromyographic responses to train-of-four (TOF) ulnar nerve stimulation repeated every 20 seconds. Seventy-five patients served as the control group and received 1 mg.kg-1 SCC without pretreatment with VB or PB. Other 191 patients were divided into three groups according to the type and dosage of pretreatment as follows: VB 20 micrograms.kg-1, VB 14 micrograms.kg-1 and PB 20 micrograms.kg-1. Five minutes after each pretreatment. SCC 1 mg.kg-1 was administered intravenously. All patients were intubated after SCC injection and then anesthesia was maintained with nitrous oxide and enflurane. Among pretreatment groups, the maximal amplitude response to TOF stimuli and TOF ratio were depressed most by 20 micrograms.kg-1 VB and least by 20 micrograms.kg-1 PB at the time of SCC administration. All pretreatments delayed the onset time from SCC injection to maximal blockade compared with that of control group. Maximal blockade induced by SCC was significantly less in VB 20 micrograms.kg-1 group than that in other pretreatment and control groups. The duration of action of SCC was shortened by pretreatments with two dosages of VB but prolonged by PB pretreatment. TOF ratio during the recovery phase was depressed in all pretreatment groups than that in control group. It is demonstrated that a non-depolarizing muscle relaxant, VB has relatively potent antagonistic action on SCC-induced effects, although another potent agent, PB exerts antagonistic action only slightly.

Effect of suxamethonium, pancuronium, neostigmine and halothane on serum cholinesterase activity.

Serum cholinesterase (Ch E) estimations were done in 30 healthy Nigerians scheduled for elective surgical procedures and were studied in two groups. Half of the patients were given general anesthesia using a muscle relaxant technique and the other half had halothane as the main anesthetic. Suxamethonium reduced Ch E by 9%, pancuronium by 25% and neostigmine by 58% compared to preinduction levels. Halothane reduced Ch E by 7% and 15% at 10 minutes and 24 hours postanesthetic respectively, compared to preinduction levels. The normal control value of Ch E in 30 healthy Nigerians was on the lower side of the normal range, observed mostly in Caucasians.

[Histamine release due to ganglion blocking agent and muscle relaxants from rat mast cells].

The mechanisms of histamine release due to d-tubocurarine from rat mast cells have long been known to anesthesiologists, such as degranulatory process, Ca++ dependent process and energy coupled process. However, not much is known about histamine release due to some drugs such as trimethaphan and muscle relaxants other than d-tubocurarine, like alcuronium, pancuronium or succinylcholine, although many clinical reports related to hypersensitivity reactions due to muscle relaxants can be found. In this experiment, the histamine releasing activities of trimethaphan and muscle relaxants were examined using the laboratory model created by Ellis (1970) who reported the selective release of histamine due to d-tubocurarine. Also observed the effects of autonomic neuro-effective drugs such as theophylline, isoproterenol or carbamylcholine on histamine release due to d-tubocurarine. From this experiment, it is suggested that trimethaphan releases histamine through nonselective process but muscle relaxants release histamine selectively. It is also found that pancuronium had little effects on rat mast cells and its histamine releasing activity was selective, if any. Histamine release from rat mast cells due to d-tubocurarine was clearly depressed by pretreatment of theophylline or isoproterenol. In the case of carbamylcholine, low doses inhibited histamine release, but higher doses allowed histamine to be liberated from mast cells. From these findings, it is concluded that some drugs like theophylline or isoproterenol may diminish the side effects of d-tubocurarine and perhaps some other muscle relaxants. Also, as theophylline and isoproterenol are concerned, increase of cyclic AMP may play a role in the inhibition of histamine release. The data using carbamylcholine suggested that the cholinergic receptors on the rat mast cells may be involved through the process of histamine release.