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Biomedical subjects

S A Feldman

Publications and source records attributed to S A Feldman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Sensitivity to second dose of mivacurium.

The sensitivity of patients to a second dose of mivacurium has been studied following complete recovery of the twitch response after > 95% neuromuscular block produced by a systemic bolus of the drug. In further experiments we have excluded one arm from the effect of a systemic bolus ED95 dose of mivacurium for 100 s so as to obtain two different levels of neuromuscular block in the two arms of the same patient. Upon recovery from the block in the paralysed arm the dose response of both arms to a second dose of mivacurium was studied in order to investigate the effect of the amount and duration of block upon second dose sensitivity. An approximately 50% diminution in the ED95 dose requirement of mivacurium was found following complete recovery from an ED95 dose in spite of the rapid plasma clearance of this drug. A similar increase in sensitivity was observed in the arm that had been excluded for 100 s from the peak effect of the drug. It was concluded that the second dose sensitivity was not due to a receptor effect or to residual drug in plasma.

Adult↗
PubMed1994

Curare modification of suxamethonium blockade.

Tubocurare (0.125 mg.kg-1 or 0.25 mg.kg-1) was injected 10 s before 1 mg.kg-1 suxamethonium in patients anaesthetised with enflurane 1-1.5%. Measurement of electromyographic response was recorded using a 0.2 Hz train-of-four every 20 s. The modified blocks were slower in onset, of lesser intensity, and of shorter duration than that of suxamethonium alone, but were much closer to those of suxamethonium than of tubocurare. However, the train-of-four fade observed during onset of the modified blocks were similar to that of their tubocurare controls and significantly different from the suxamethonium group. We conclude that effective amounts of tubocurare are present in the neuromuscular junction within the 30 s following intravenous injection of the drugs, and this affects the onset of action of the suxamethonium block. The presence of train-of-four fade during a predominantly agonist block is difficult to explain on the basis of diminished acetylcholine release and a postsynaptic site of action of suxamethonium.

Adult↗
PubMed1994

Rocuronium--onset times and intubating conditions.

Many factors influence the minimum time required to achieve an easy and successful tracheal intubation after a non-depolarizing relaxant. The ideal study design has never been achieved in practice: an overall picture of the efficacy of rocuronium depends on careful interpretation of studies with different methodologies, which have usually compared the new drug with vecuronium or suxamethonium, currently the best alternatives. Despite lack of supporting animal data, the rapidity of onset of rocuronium in man appears to be due to an early presynaptic effect. Observations which are difficult to explain are that increasing the dose above about 2 x ED90 does not shorten the time to onset and 'priming' also has no beneficial effect. Although some studies have produced evidence that rocuronium can produce smooth easy intubation conditions in 60 s, 90 s would appear to be closer to the time when excellent conditions can be guaranteed. Whether this is an acceptable alternative to the 45 s or so needed after suxamethonium is a matter of clinical judgement which only testing in practice will answer.

Androstanols↗
PubMed1993

Tetanic fade during recovery from vecuronium block: comparison of systemic and isolated forearm administration.

We have compared the degree of tetanic fade relative to twitch depression occurring after isolated forearm block with vecuronium and that after systemic i.v. injection. Fifteen patients received either vecuronium 0.3 mg into an isolated forearm or vecuronium 0.05 mg kg-1 systemically. Adductor pollicis mechanomyography was used to monitor recovery of twitch height at 0.2 Hz. At 25, 50, 75 and 100% recovery of twitch height, a 5-s, 50-Hz tetanus was administered and tetanic fade ratio measured. There was significantly less tetanic fade in the isolated forearm group (P < 0.01; unpaired ttest) at 25, 50 and 75% twitch height. This suggests that twitch depression and tetanic fade are independently mediated effects of vecuronium.

Adult↗
PubMed1993

Comparison of recovery index of rocuronium or vecuronium with simultaneously administered pancuronium in the isolated forearm.

A series of isolated forearm experiments is described in which rocuronium or vecuronium were injected into one arm, and pancuronium injected simultaneously into the contralateral arm. The time for 25%-75% twitch recovery (recovery index) was recorded in both arms. The recovery indices of rocuronium and vecuronium were similar, but that of pancuronium significantly longer. Because the recovery indices compared in any one experiment occurred in the presence of identical background plasma concentration, the differences observed in recovery index between pancuronium and either rocuronium or vecuronium are due to different rates of dissociation from the effect compartment at the neuromuscular junction.

Androstanols↗
PubMed1993

The effect of residual receptor occupancy on sensitivity to repeated vecuronium.

Cumulative dose-response curves were obtained for vecuronium in 10 patients anaesthetised with thiopentone, enflurane and nitrous oxide using adductor pollicis mechanomyography. Five patients received vecuronium systemically, which was repeated at 100% twitch recovery to obtain initial and repeat curves. Another five patients received 0.3 mg vecuronium into an isolated forearm and at 100% recovery of this arm received vecuronium systemically to obtain simultaneous dose-response curves in both the previously isolated and nonisolated arms. There was no significant difference between the calculated ED50 obtained after initial systemic administration [16.2 (1.7) micrograms.kg-1], after recovery in the previously isolated arm [14.8 (2.0) micrograms.kg-1] and simultaneously in the nonisolated arm [16.1 (2.9) micrograms.kg-1]. The ED50 obtained after repeated systemic administration was significantly reduced [8.2 (2.9) micrograms.kg-1]. These results suggest that the reduction in ED50 at 100% twitch recovery from systemic vecuronium is not due to residual drug at the biophase/receptor but to drug persisting in the plasma.

Anesthesia, General↗
PubMed1993

Effect of voluntary tetanus on recovery of vecuronium block in the isolated forearm.

This study was conducted to investigate the effect of voluntary tetanus on the recovery from neuromuscular block produced by a nondepolarising drug, vecuronium, in the isolated forearm. We have studied the recovery indices and train of four fade at different levels of recovery following vecuronium in both isolated forearms simultaneously, in six sets of experiments. In one hand the volunteer performed a maximum contraction of his thumb repeatedly at fixed intervals. We found that following voluntary tetanus there is an increased rate of recovery from nondepolarising neuromuscular block; mean Recovery Index (7.4, SD 0.97) compared to control Recovery Index (10.55, SD 2.58), p < 0.05. The train-of-four fade also showed a sustained reduction in the isolated forearm which underwent voluntary tetanus. During the later phase of recovery the train-of-four fade showed significant difference statistically (p < 0.01). The findings of this study supports the hypothesis that more rapid recovery associated with voluntary tetanus is due to a reduction in the presynaptic block thus resulting in an increased rate of transmitter release.

Forearm↗
PubMed1993

Recovery from pancuronium and vecuronium administered simultaneously in the isolated forearm and the effect on recovery following administration after cross-over of drugs.

If recovery of neuromuscular block in the isolated arm is determined by biophase binding, then a significant amount of drug will still be present in the biophase at 50% recovery of twitch response. To test this hypothesis we administered pancuronium at 50% recovery from vecuronium block and vecuronium at 50% recovery from pancuronium block in the isolated forearms of volunteers. To ensure that any effect of drug released into the plasma did not affect the results, both experiments were performed simultaneously, one in each forearm of each volunteer. Control experiments were performed to determine the effect of subsequent injections of the same drug at 50% recovery and of subsequent injections of the alternative drug (i.e., vecuronium following pancuronium and pancuronium following vecuronium) at 100% recovery of the twitch response. Prior administration of vecuronium significantly shortened the recovery from subsequent pancuronium when administered at 50% recovery, but not 100% recovery, and pancuronium significantly increased the recovery rate of vecuronium when given at 50% recovery but not 100% recovery. These findings support the concept of biophase binding of nondepolarizing neuromuscular blocking drugs.

Anesthesia Recovery Period↗
PubMed1993

Resistance to decamethonium neuromuscular block after prior administration of vecuronium.

Prior administration of nondepolarizing neuromuscular blocking drugs reduces the potency of subsequently administered succinylcholine. To assess whether this interaction is also observed with the depolarizing drug, decamethonium, the potency of decamethonium alone and decamethonium after vecuronium (10 micrograms/kg) were assessed using a cumulative dose-response technique in two groups of six healthy patients each. Patients were premedicated with meperidine and promethazine and anesthetized with thiopental, isoflurane, and nitrous oxide in oxygen. Twitch tension was monitored using adductor pollicis mechanomyography in response to ulnar nerve stimulation at 0.1 Hz. The mean (SEM) dose of decamethonium producing 80% twitch tension depression (ED80) when administered alone was 37 (4.0) micrograms/kg. After recovery of twitch tension (but persistence of train-of-four fade) from vecuronium, the mean (SEM) ED80 for decamethonium was increased to 89 (4.4) micrograms/kg (P < 0.01). The shift to the right of the dose-response curve for decamethonium was nonparallel. Antagonism is observed when decamethonium is administered after a small dose of vercuronium; this interaction, which is also seen with succinylcholine, is likely to be a feature of depolarizing block. Nonparallel shift of the dose-response curve to decamethonium indicates that this is not likely to be a simple agonist-antagonist effect at a single site.

Adult↗
PubMed1991

The effects of intravenous clonidine on ventilation.

The effects of clonidine, an alpha 2 adrenergic agonist, on ventilation were studied in a group of adult volunteers. The ventilatory variables measured were minute ventilation, respiratory rate, end-tidal carbon dioxide tension and the response to carbon dioxide challenge. We found no differences in minute ventilation, respiratory rate and end-tidal carbon dioxide tension, before and after clonidine administration. However, the ventilatory response to carbon dioxide was significantly attenuated following clonidine, suggesting that clonidine has respiratory depressant effects.

Adult↗
PubMed1991

The cuffed pharyngeal airway.

A new self-retaining nasopharyngeal airway is described. The clinical performance of this airway was assessed in 100 patients during anaesthesia with spontaneous respiration. The physical behaviour of the airway was investigated in four patients. In an additional 25 patients the tube was used via the oral route. Although designed for use by the nasal route, the airway can be used as a self-retaining oropharyngeal airway.

Adult↗