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Biomedical subjects

B J Pollard

Publications and source records attributed to B J Pollard.

At least 73 records · Page 4Linked to original sources

Use of atracurium or vecuronium to prolong the action of tubocurarine.

Forty patients received tubocurarine in a dose greater than ED90. When neuromuscular function had recovered to amplitude of the first contraction of the train-of-four equals 10% of control, a small increment of atracurium or vecuronium was administered, repeating the same increment at each subsequent recovery to 10%. The intensity and duration of the neuromuscular block following the first increment was always greater than that of subsequent increments. The duration and intensity of the block was progressively reduced with subsequent increments until the responses to further increments were unchanged. These final means at steady state were: group 1 (atracurium 1.1 mg) 6.4 (0.3) min; group 2 (atracurium 2.0 mg) 8.2 (0.9) min; group 3 (vecuronium 0.25 mg) 5.8 (0.4) min; group 4 (vecuronium 0.5 mg) 13.2 (0.4) min.

Adult↗

Doxapram and the neuromuscular junction.

We have studied the action of doxapram on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Doxapram augmented neuromuscular transmission in a dose-related manner when a threshold concentration of 5 x 10(-5) mol litre-1 had been exceeded. The activity of the acetylcholinesterase in rat diaphragm has been examined also in the presence of doxapram. No inhibitory effect was seen in the concentration range which augmented neuromuscular transmission, thus excluding cholinesterase inhibition as the underlying mechanism. In contrast, in the presence of partial neuromuscular block, a dose-related depression of neuromuscular transmission with doxapram was revealed. This was greatest when the neuromuscular blocking agents possessed significant presynaptic activity (beta-bungarotoxin and tubocurarine). In this situation any facilitatory action of doxapram was severely reduced or abolished. In contrast, the facilitatory effects of doxapram were apparent in the presence of partial block produced by agents with less or no presynaptic activity (pancuronium and alpha-bungarotoxin). This study suggests that doxapram has a presynaptic facilitatory action at the neuromuscular junction. In the presence of partial neuromuscular block, an inhibitory action is revealed which may be post-junctional. The concentrations of doxapram at which these effects appear are approximately five times greater than those reached in plasma after a standard clinical dose.

Acetylcholinesterase↗

Concentrations of atracurium and laudanosine in cerebrospinal fluid and plasma during intracranial surgery.

Concentrations of atracurium and laudanosine in cerebrospinal fluid (CSF) and plasma were assayed in nine patients receiving atracurium infusions of 111-251 min duration to maintain neuromuscular block during intracranial surgery. The total dose of atracurium was 1.57-2.60 mg kg-1 and the plasma concentration of atracurium was 1.27-5.44 micrograms ml-1. Concentrations of laudanosine in CSF and plasma increased during the infusion period, and after 125-140 min reached means of 202.5 ng ml-1 and 1448.7 ng ml-1, respectively. The highest recorded concentration of laudanosine in CSF was 570 ng ml-1, in one of two CSF samples found to contain atracurium. After operation, two patients had fits, but these were not thought to be related to laudanosine. It is concluded that during infusion of atracurium, laudanosine accumulates in both plasma and CSF.

Adult↗

Obstructive sleep apnoea.

A patient with obstructive sleep apnoea is described, who required admission to an intensive care unit on two separate occasions within 2 months. The first admission was after anaesthesia for operation on the upper airway. The second occurred after a relative overdose of an opioid analgesic was administered. The diagnosis, treatment and anaesthetic management of patients with this syndrome are discussed.

Airway Obstruction↗

The effect of acutely administered phenytoin on vecuronium-induced neuromuscular blockade.

Phenytoin was administered intravenously in a dose of 10 mg kg to a group of patients in whom steady state neuromuscular blockade had been established with an infusion of vecuronium. A control group of patients were given 0.9% saline instead of phenytoin. Administration of phenytoin produced significant augmentation of neuromuscular blockade (p less than 0.001). The possible mechanism of this effect is discussed.

Adult↗

Differing interactions between hexamethonium and tubocurarine, pancuronium or alcuronium at the neuromuscular junction.

The action of hexamethonium has been investigated in the rat phrenic nerve-hemidiaphragm preparation, alone and in combination with the neuromuscular blocking agents tubocurarine, pancuronium and alcuronium. Hexamethonium alone in concentrations between 3.55 x 10(-3) and 7.1 x 10(-3) mol litre-1 produced neuromuscular blockade in a dose-dependent manner. Low concentrations of hexamethonium antagonized the neuromuscular blocking effect of all three neuromuscular blocking drugs, less with tubocurarine than with the other two. Increasing the concentration of hexamethonium produced potentiation of the neuromuscular blocking effect, this being greater with tubocurarine than with either pancuronium or alcuronium. The cholinesterase activity in rat diaphragm homogenates was inhibited by hexamethonium. This inhibition was only significant at concentrations greater than those which resulted in antagonism and cannot, therefore, explain the observed antagonism. The mechanism of these observations is discussed with respect to the known behaviour of a combination of antagonists acting within a receptor system.

Alcuronium↗

A method of detecting oesophageal intubation or confirming tracheal intubation.

A method of testing the location of an endotracheal tube, in the trachea or oesophagus, was subjected to trial. The test involves drawing back on the plunger of a 50 ml syringe connected with airtight fittings to the endotracheal tube connector, with the endotracheal tube cuff deflated. The ability to withdraw 30 ml of air confirms tracheal intubation. When marked resistance to withdrawal of the plunger occurs and on release the plunger rebounds to its original position the oesophagus has been intubated. The method was 100% accurate in fifty intubations, 25 tracheal and 25 oesophageal. The technique has been in routine use by one author for several years without giving an incorrect answer and enthusiastic use by other authors is producing the same result.

Adult↗

Interactions of vecuronium and atracurium in an in vitro nerve-muscle preparation.

Atracurium and vecuronium were compared when given alone and in combination in the in vitro rat phrenic nerve-hemidiaphragm preparation stimulated via the phrenic nerve. The slopes of the log dose response curves of atracurium and vecuronium were parallel; their ED50s were 1.12 +/- 0.0035.10(-5)M and 5.89 +/- 0.16.10(-6)M, respectively. The combination's log dose response curves were significantly shifted to the left when compared with those of either relaxant alone; an increased potency is displayed by the combination. These observations indicate nondepolarizing muscle relaxant synergy for the combination of equal proportions of vecuronium and atracurium. The synergistic interaction of vecuronium and atracurium in this in vitro-model is not dependent on pharmacokinetic factors such as uptake, distribution, and biodegradation as are present in the in vivo animal models and in humans. Synergy of vecuronium and atracurium in vitro is a new finding and is consistent with hypotheses of multiple receptor sites and different modes of action of the "competitive" neuromuscular blocking agents. This degree of synergy, seen in the in vitro animal data, if extrapolatable to humans, is probably of little clinical significance.

Animals↗

Euthanasia.

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Ethics, Medical↗

The neuromuscular blocking effect of trimetaphan alone and in combination with different non-depolarizing muscle relaxants in the rat.

The effect of trimetaphan alone and in combination with pancuronium, tubocurarine or metocurine (dimethyl tubocurarine) has been examined on the rat phrenic nerve diaphragm preparation. Trimetaphan alone produced neuromuscular blockade in an all-or-none fashion once a concentration of between 2.39 X 10(-4) and 3.00 X 10(-4) M had been exceeded. Concentrations of trimetaphan below this threshold produced a dose-dependent potentiation of all three non-depolarizing relaxants studied. This potentiation was equal for tubocurarine and metocurine, but less for pancuronium.

Animals↗