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Biomedical subjects

N T Campkin

Publications and source records attributed to N T Campkin.

13 recordsLinked to original sources
PubMed1995

No effect of circulating drug upon isolated forearm block.

Controversy exists as to whether the recovery of isolated arm blockade is primarily determined by resultant plasma drug concentrations, or by the affinity of the drug for the biophase. We have investigated the effect of the circulating drug produced by the isolated forearm experiment upon its recovery profile. Paralysis from retrograde spread of drug after the intravenous injection of 20 ml saline containing vecuronium 0.3 mg into a forearm isolated from the circulation was achieved in three groups of five experiments. Group 1 were used as controls, the tourniquet being released after 3-4 min and the recovery of block observed. In group 2 the tourniquet was similarly released but a repeat dose of vecuronium 0.3 mg was administered into the systemic circulation at 10% recovery. In group 3 the tourniquet was released at 50% twitch depression and the repeat dose of vecuronium 0.3 mg given when the twitch height had recovered to that level. The mean (SD) 25% to 75% recovery indices of groups 1, 2 and 3 were: 9.2 (2.4), 8.7 (1.2) and 9.9 (1.9) min. There was no noticeable effect on the recovery slope of any of the traces when the second dose of myoneural blocker was given systemically in groups 2 and 3. The findings indicate that the main determinant of recovery of the isolated forearm experiment is not its plasma drug concentration but a mechanism which maintains the drug in the effect compartment.

Forearm↗
PubMed1994

Recovery of mivacurium and doxacurium versus vecuronium in the isolated forearm.

To assess rate of biophase recovery, the recovery from neuromuscular block with mivacurium in the isolated forearm was compared with that from vecuronium simultaneously administered into the other isolated forearm of six volunteers. In a second series of similar experiments, recovery from doxacurium was compared with that from vecuronium. Neuromuscular block was monitored using the adductor pollicis mechanomyographic response to ulnar nerve stimulation at 0.2 Hz. Comparable degrees of maximum twitch tension depression were obtained in each series. In the first series, mean (SD) 25-75% recovery index for mivacurium was 8.4 (1.5) min and 10.5 (1.9) min for vecuronium. In the second series, mean (SD) recovery index for doxacurium was 18.3 (4.2) min and 12.2 (5.0) min for vecuronium. The recovery index of doxacurium in the isolated forearm was significantly greater, and the recovery index of mivacurium significantly less, than the recovery index of simultaneously administered vecuronium. Mivacurium block in the isolated forearm recovers rapidly, although not faster than after systemic injection; this is consistent with a drug that is retained in the biophase despite rapid plasma metabolism. Doxacurium block in the isolated forearm is slow to recover, compared with vecuronium; this suggests that high affinity for the biophase may contribute to its long duration of action.

Forearm↗
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↗
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

The rebreathing characteristics of the Hudson oxygen mask.

A lung model was used to study the effect of varying minute ventilation, oxygen flow and inspiratory : expiratory ratio on the rebreathing characteristics of the Hudson oxygen mask. The onset of rebreathing was detected using two different sets of criteria; those defined by Kain et al. and Humphrey. The onset of rebreathing was also quantified in terms of the inspired volume of carbon dioxide and increases in deadspace. The magnitude of rebreathing was increased by reducing oxygen inflow and increasing minute ventilation. Variation in I : E ratio between 1 : 1 and 1 : 4 had little effect on rebreathing. Using the clinical criteria of Kain et al, the onset of rebreathing was detected when oxygen inflow/minute ventilation ratio was reduced below 0.78 on average. With the other criterion, rebreathing occurred when the ratio was 0.46.

Carbon Dioxide↗
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

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↗