Biomedical subjects
D R Bevan
Publications and source records attributed to D R Bevan.
Anticholinesterase antagonism of succinylcholine phase II block.
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Neostigmine antagonism of succinylcholine phase II block: a comparison with pancuronium.
To assess the efficacy of neostigmine antagonism of succinylcholine phase II block, succinylcholine infusions were given to 17 patients for durations varying from 44 to 192 minutes. A control group (17 patients) received a pancuronium infusion for similar times. Ninety per cent neuromuscular block was maintained in these two groups by adjustment of the infusion rates and, in a third group, with intermittent doses of pancuronium. Neuromuscular transmission was monitored with train-of-four stimulation every 12 seconds and anaesthesia was maintained with N2O-O2-enflurane. Ten minutes after the infusion was stopped, atropine and neostigmine were given to all patients who received pancuronium and to 11 patients in the succinylcholine group whose train-of-four ratio (T4/T1) was less than 0.7. During the subsequent 15 minutes, recovery was more rapid in the succinylcholine group than in either the pancuronium-infusion or pancuronium-bolus groups. It is concluded that succinylcholine-induced phase II block can be safely and rapidly antagonized with neostigmine.
Prolonged suxamethonium infusion during nitrous oxide anaesthesia supplemented with halothane or fentanyl.
The neuromuscular blockade produced by a prolonged infusion of suxamethonium was studied using train-of-four stimulation in 40 patients receiving either halothane-nitrous oxide or fentanyl-nitrous oxide anaesthesia. Initially, a depolarizing (phase I) block was observed in all patients followed by phase II block which was associated with tachyphylaxis to suxamethonium; the latter changes occurring more rapidly in the halothane group. Infusions were continued for more than 150 min in 17 patients and there was a late decrease in suxamethonium requirement in those who received halothane, but not fentanyl. Ten minutes after the suxamethonium infusion was stopped, most patients received neostigmine which was followed by rapid recovery of neuromuscular transmission.
Long-term succinylcholine infusion during isoflurane anesthesia.
The characteristics of the neuromuscular blockade produced by prolonged succinylcholine infusion were compared in 40 patients anesthetized with either nitrous-oxide-isoflurane (0.75-1.50% inspired) or nitrous-oxide-fentanyl. Neuromuscular transmission was monitored using train-of-four stimulation and the infusion rate was adjusted to keep the first twitch at 10-15% of its control value. Initially, all patients exhibited a depolarizing-type block, and the infusion rates were similar in the isoflurane (61 micrograms . kg-1 . min-1) and fentanyl (57 micrograms . kg-1 . min-1) groups. Tachyphylaxis developed in both groups and correlated well with the onset of non-depolarizing (phase II) block. Both occurred sooner and at a lower cumulative dose in the isoflurane groups. After 90 min, infusion rates were similar in both groups (isoflurane: 107 micrograms . kg-1 . min-1, fentanyl;: 93 micrograms. kg-1 . min-1). After the infusion was stopped, the recovery of the train-of-four ratio was inversely related to the dose and duration of exposure to succinylcholine, and was slower with nitrous-oxide-isoflurane anesthesia. After 10 min of recovery, patients receiving isoflurane exhibited train-of-four ratios of 0.5 or less after 8.5 mg/kg succinylcholine and 103 min. Corresponding figures for fentanyl patients were 13 mg/kg and 171 min. The block in all 13 patients (eight with isoflurane, five with fentanyl) who did not recover spontaneously was antagonized successfully with atropine and neostigmine. It was concluded that with succinylcholine infusion of 90 min or less, isoflurane accelerates the onset of tachyphylaxis and phase II neuromuscular block without affecting succinylcholine requirements. These results, with isoflurane, were similar to those reported previously with enflurane or halothane.
Potentiation of succinylcholine phase II block with isoflurane.
To determine the effect of isoflurane upon phase II block 20 patients were given succinylcholine by infusion at a rate which maintained the twitch tension of the adductor pollicis muscle at 10% of control for 2 to 4 h. The patients were assigned randomly to either nitrous-oxide-isoflurane (0.75-1.5% inspired) or nitrous-oxide-fentanyl for maintenance of anesthesia, and neuromuscular activity was monitored using train-of-four stimulation. Tachyphylaxis to succinylcholine was observed in both groups but this was followed, in the isoflurane group but not in the fentanyl group, by a decrease in succinylcholine requirement. This decrease was related to the extent of phase II block present. It is concluded that isoflurane potentiates succinylcholine phase II block although the mechanisms involved are not necessarily the same as in the potentiation of nondepolarizing neuromuscular blocking drugs.
Neostigmine and edrophonium as antagonists of pancuronium in infants and children.
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Measurement of pleural pressure with esophageal balloon in anesthetized humans.
Simultaneous measurement of tracheal and esophageal pressures during occluded inspiratory efforts (occlusion test) was used to assess the validity of the esophageal balloon technique in anesthetized supine subjects. Ten ASA 1 patients undergoing general anesthesia (halothane 1 MAC, nitrous oxide 70%, and oxygen) for minor surgery were studied. Esophageal pressure (Pes) was measured using a 5-cm-long balloon and was plotted against tracheal pressure (Pt). Occlusion tests were performed at end expiration with the balloon top positioned 5, 10, 15, and 20 cm above the cardia. The results show that with the balloon positioned at the classical level of 10 cm above the cardia, the difference between delta Pes and delta Pt did not exceed 8% in seven of 10 subjects. In the remaining three, however, the difference between delta Pes and delta Pt ranged between +20% and -40%. By repositioning the balloon to 5 or 15 cm above the cardia, a locus was found in all subjects where the difference is less than 10%. We conclude that the esophageal balloon technique can be used in anesthetized supine subjects to give reliable measurements of changes in pleural pressure, provided that it is validated with the occlusion test.
Pancuronium requirements during hypothermic cardiopulmonary bypass in man.
Eight patients were studied to determine the changes in pancuronium requirements during hypothermic cardiopulmonary bypass. They were anaesthetised with fentanyl as the principal agent, ventilated with oxygen and the neuromuscular junction was monitored using train-of-four stimulation. After a bolus dose of pancuronium an infusion was used to maintain the first twitch of the train-of-four at 5-15 per cent of control. Before bypass the mean pancuronium infusion rate was 0.52 (SD 0.16) micrograms/kg/min. There was a small, brief increase in requirement with the initiation of bypass to 0.62 (SD 0.38) micrograms/kg/min, which was followed by a decrease of more than 80 per cent during hypothermia to 0.08 (SD 0.03) micrograms/kg/min. Rewarming was associated with a rapid increase in requirement to 0.64 (SD 0.17) micrograms/kg/min, which decreased to 0.33 (SD 0.23) micrograms/kg/min when normothermia was re-established.
Succinylcholine in obstetrics.
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Twitch depression and train-of-four ratio after antagonism of pancuronium with edrophonium, neostigmine, or pyridostigmine.
During N2O-O2-halothane anesthesia pancuronium (3 mg/70 kg) was antagonized with neostigmine (2.5 or 5 mg/70 kg), pyridostigmine (10 or 20 mg/70 kg), or edrophonium (50 or 100 mg/70 kg) in 36 human subjects (6 in each group). Reversal was attempted at 10% spontaneous recovery of muscle twitch, which was measured using train-of-four stimulation. When first twitch tension was less than 70% of the control it was found that for the same tension, the train-of-four ratio was greater with edrophonium than with neostigmine, and greater with neostigmine than with pyridostigmine. It was concluded that the three antagonists have different mechanisms of action. In comparison with neostigmine, edrophonium is more and pyridostigmine is less effective at presynaptic (or fade) receptors.
Clinical experience with ORG NC45 (norcuron) as the sole muscle relaxant.
The neuromuscular effects of ORG NC45, used as the sole muscle relaxant, were compared with a succinylcholine-pancuronium sequence in patients during nitrous oxide-fentanyl anaesthesia. The subjects were divided into four groups with ten in each group. After induction of anaesthesia they received either succinylcholine, 1 mg . kg-1 or ORG NC45 in doses of 50, 70 or 90 micrograms . kg-1 and tracheal intubation was done 90 seconds later. Neuromuscular transmission was monitored using train-of-four stimulation. Succinylcholine produced 100 per cent block with uniformly excellent intubating conditions whereas the three doses of ORG NC45 were associated with blocks of 7.5, 18.7 and 30.7 per cent and acceptable conditions in only 30 per cent of subjects. Muscle relaxation was maintained in the NC45 groups with increments of 10 micrograms . kg-1 and in the succinylcholine group with pancuronium, initially as a bolus of 40 micrograms . kg-1, followed by increments of 5 mg . kg-1. All increments were given at 10 per cent recovery of twitch height. The overall requirement to maintain 90 per cent block with pancuronium was 1.1 microgram/kg-1 . min-1 compared with 1.28 microgram . kg-1 . min-1 with ORG NC45. No cumulative effects were seen with either drug during the first hour of neuromuscular blockade. At the end of the operation the neuromuscular block was antagonized with atropine 18 micrograms . kg-1, and neostigmine 36 micrograms . kg-1 and recovery was significantly more rapid with NC45 than pancuronium. We conclude that the lack of cumulation, easy reversibility and lack of cardiovascular effects suggest that NC45 has advantages over currently available non-depolarizing muscle relaxants but that its onset of action is too slow for rapid intubation.
Effect of enflurane and fentanyl on the clinical characteristics of long-term succinylcholine infusion.
The characteristics of the neuromuscular block produced by prolonged succinylcholine infusion were compared in 40 patients anaesthetized with either nitrous oxide with enflurane (1-2 per cent inspired) or nitrous oxide and fentanyl. Neuromuscular transmission was monitored using train-of-four stimulation and the infusion rate was adjusted to keep the first twitch at 10-15 per cent of its control value. Initially, all patients, exhibited a depolarizing-type block all twitches of the train-of-four being roughly the same size, and the infusion rates were similar in the enflurane (54 microgram X kg-1/min) and the fentanyl (58 microgram X kg-1/min) groups. Tachyphylaxis developed later in both groups and correlated well with the onset of phase II block (dual block). This occurred sooner and at a lower cumulative dose in the enflurane group. Fourth to first twitch ratios decreased to 50, 25 and 0 per cent in 31, 46 and 59 minutes in the enflurane group, at cumulative succinylcholine doses of 2.2, 3.2 and 4.2 mg X kg-1 respectively. Corresponding figures for the fentanyl group were 52, 73 and 86 minutes, with dose of 3.4, 5.0 and 5.9 mg X kg-1. Infusion rates increased markedly after establishment of dual block, but were similar with enflurane (0.99 mg X kg-1/min) and fentanyl (1.12 mg X kg-1/min). Ten minutes after stopping the infusion fourth to first twitch ratios failed to reach 50 per cent in most patients given enflurane who had received more than 6 mg X kg-1 succinylcholine over more than 90 minutes. Corresponding figures for fentanyl patients were 13 mg x kg-1 and 150 minutes. The block in all 15 patients (9 enflurane, 6 fentanyl) who did not recover spontaneously was successfully antagonized with atropine and neostigmine.
Meperidine infusion for postoperative analgesia in grossly obese patients.
Postoperative analgesia was provided to nine grossly obese patients with a continuous intravenous meperidine infusion. The narcotic was infused at an initial rate of 1.3 mg . min-1 for 45 minutes, then 0.7 mg . min-1 for 30 minutes followed by 0.5 mg . min-1 for the next 24 hours. Pain was assessed at hourly intervals, serial blood samples were taken for measurement of plasma meperidine concentrations, and respiratory function was assessed by serial measurement of vital capacity and arterial blood gas analysis. Analgesia was gradual in onset and from six hours after commencement of the infusion, seven of the patients suffered little or no pain. Plasma meperidine concentrations reached a peak of 0.33 +/- 0.05 microgram . ml-1 at one hour decreased gradually after three hours. Surprisingly, there was poor correlation between analgesia and plasma meperidine concentration. All patients breathed spontaneously and maintained satisfactory blood gas tensions. However, there was a marked reduction in postoperative vital capacity. Thus meperidine administered by continuous intravenous infusion can provide good postoperative analgesia in the obese patient without producing respiratory depression. However, the lack of correlation between analgesia and plasma narcotic concentration suggests that further study is required before intravenous regimes can be prescribed by application of pharmacokinetic principles.
Antagonism of pancuronium in renal failure: no recurarization.
Neuromuscular transmission was measured using train-of-four stimulation, during and after anaesthesia, in 20 patients with end-stage renal failure. Neuromuscular blockade was provided with pancuronium in single doses of either 3 or 6 mg per 70 kg, and antagonized at 10% recovery with atropine and neostigmine 2.5 mg per 70 kg. Reversal was followed by progressive recovery of muscle twitch in every patient during the 3 h of the study. Recovery was more rapid after the smaller dose of pancuronium and was inversely correlated with the duration of blockade. It is concluded that, when pancuronium is antagonized with neostigmine in patients with renal failure, neuromuscular transmission recovers without evidence of recurarization. However, when large doses of pancuronium are antagonized with neostigmine 2.5 mg, recovery may be insufficient to ensure normal ventilatory function.
Impaired neostigmine antagonism of pancuronium during enflurane anaesthesia in man.
We have compared the rates of recovery of pancuronium-induced neuromuscular blockade after administration of neostigmine during anaesthesia maintained with nitrous oxide and intermittent narcotics, halothane or enflurane. Thirty patients were studied in whom anaesthesia was maintained with 70% nitrous oxide in oxygen with: fentanyl or thiopentone, halothane (0.55-0.65% end-tidal), or enflurane (1.3-1.4% end-tidal). Muscle twitch response was measured using train-of-four stimulation. Pancuronium 3 mg/70 kg was antagonized with neostigmine 2.5 mg/70 kg at 10% spontaneous recovery of the first twitch of the train compared with control. There were no significant differences between the times to 10% spontaneous recovery of the first twitch or the rates of train-of-four recovery after neostigmine when the narcotic and halothane groups were compared. However, enflurane anaesthesia, in comparison with fentanyl, was associated with a significant increase in the time to 10% recovery (57.9 +/- 6.0 min v. 35.4 +/- 7.0 min) and with decreases in the train-of-four recoveries at 4, 5, 10, 20 and 30 min after neostigmine. We conclude that, under the conditions of this study, the antagonism of pancuronium-induced neuromuscular blockade with neostigmine was impaired during enflurane but not halothane anaesthesia.
Fentanyl infusion anesthesia for aortocoronary bypass surgery: plasma levels and hemodynamic response.
Plasma fentanyl concentrations were measured by radioimmunoassay in patients during aortocoronary bypass surgery and correlated with hemodynamic responses to surgical stimulation. Thirty patients scheduled for aortocoronary bypass surgery were divided into three groups of 10. Patients in group 1 received fentanyl, 30 micrograms/kg, as a loading dose followed by an infusion of 0.3 microgram/kg/min; those in group 2 received 40 micrograms/kg as a loading dose followed by an infusion of 0.4 microgram/kg/min; and those in group 3 received 50 micrograms/kg as the loading dose followed by an infusion of 0.5 microgram/kg/min. The total dose of fentanyl administered to each group up to the time of rewarming on cardiopulmonary bypass was 60 micrograms/kg, 90 micrograms/kg, respectively. Each of the dose regimens produced stable plasma concentrations starting approximately 20 minutes after induction and continuing until the infusion was discontinued. Patients in group 1 had a mean plasma concentration of 10 to 12 ng/ml in the stable period compared with 12 to 14 ng/ml in group 2 and 15 to 18 ng/ml in group 3. Fewer patients in group 3 responded to intubation and surgical stimulation than in the other groups, although the differences between groups were not statistically significant. Response to stimulation was treated by the administration of droperidol or volatile anesthetic agents. At a plasma concentration of 15 ng/ml, 50% of patients had an increase in systolic blood pressure which required treatment. This minimal intra-arterial concentration, analogous to MAC, can be achieved by the administration of fentanyl as a loading dose of 50 micrograms/kg followed by an infusion of 0.5 microgram/kg/min.
Plasma cholinesterase activity and tachyphylaxis during prolonged succinylcholine infusion.
Fifteen patients were studied during general anesthesia (nitrous oxide-fentanyl, N = 7 or nitrous oxide-isoflurane, N = 8) to determine the relationship between plasma cholinesterase activity and succinylcholine requirements during prolonged infusion. Using train-of-four stimulation, neuromuscular block was maintained at 90% for at least 1 hour, and plasma cholinesterase was measured at 30-minute intervals. During the infusion, succinylcholine requirements increased in every patient (tachyphylaxis), but there was no significant change in plasma cholinesterase activity. Succinylcholine requirements during the 1st hour of infusion in patients given fentanyl were correlated with preinfusion cholinesterase activity. It is concluded that tachyphylaxis to succinylcholine is not the result of increased metabolism from enzyme induction and that succinylcholine requirement is related to plasma cholinesterase activity.