Prolonged neuromuscular blockade with atracurium.
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Anesthesia↗
Biomedical subjects
F Donati
Publications and source records attributed to F Donati.
Prolonged infusion of suxamethonium in infants and children.
The neuromuscular blockade produced by a prolonged (greater than 90 min) continuous infusion of suxamethonium and measured with train-of-four stimulation was studied in 20 infants and 20 children during nitrous oxide and halothane in oxygen anaesthesia. The results were compared with a previous study in adults. Suxamethonium requirement was increased in infants and children. Mean peak infusion rates were 297 and 284 micrograms kg-1 min-1 in infants and children, compared with 134 micrograms kg-1 min-1 in adults. An initial tachyphylaxis was followed by bradyphylaxis, and the peak requirement occurred earlier in infants than in children and adults (40 v. 80-100 min). Phase II block developed during the tachyphylaxis. Recovery of neuromuscular activity commenced after stopping the infusion and was accelerated with neostigmine.
Child↗
Potency of pancuronium at the diaphragm and the adductor pollicis muscle in humans.
The measurement of force of contraction of the adductor pollicis muscle following supramaximal stimulation of the ulnar nerve has become a standard method to assess the effect of neuromuscular blocking drugs. However, the diaphragm is regarded as resistant to these drugs, and considerable residual respiratory power might still be present after total block of adductor pollicis function. To quantify this differential effect, train-of-four stimulation was applied to the ulnar and the phrenic nerves in patients under N2O-halothane anesthesia. The force of contraction of the adductor pollicis muscle was measured with a force-displacement transducer and compared with the diaphragmatic electromyogram (EMG). Pancuronium cumulative dose-response curves for both muscles were determined in 10 ASA Class I adults. The mean dose (+/- SEM) required to depress adductor pollicis and diaphragm responses to first twitch stimulation (ED50) was 29.5 +/- 3.5 micrograms/kg and 59.5 +/- 7.0 micrograms/kg, respectively. Corresponding values for ED90 were 45 +/- 5 micrograms/kg and 95 +/- 11 micrograms/kg, respectively, indicating that the diaphragm required approximately twice as much pancuronium as the adductor pollicis block, the diaphragm was only 24 +/- 4% blocked. It is concluded that the adductor pollicis response might underestimate the degree of diaphragmatic relaxation. On the other hand, the administration of pancuronium in a dose sufficient to produce total paralysis might result in the inability to antagonize neuromuscular block in all muscles.
Adult↗
Pharyngoesophageal transmucosal potential difference in normal subjects and in patients with peptic esophagitis.
Results of a study carried out on pharyngoesophageal transmucosal potential difference (PD) in normal subjects and in patients with peptic esophagitis are reported. Ten healthy individuals used as control group and 12 patients with peptic esophagitis were examined. In all the cases an electric junctional pharyngoesophageal zone was evidenced, characterized by increased negativity at the level of the upper esophageal sphincter between the pharyngeal and esophageal potential difference. No statistically significant differences were observed between the two groups as for the length of PD and its location, which was always shown to be included in the high pressure zone. In healthy subjects the pharyngoesophageal PD was -16.2 +/- 4.23 mV; in patients with peptic esophagitis PD was -25.4 +/- 8.51 mV. However, in the latter PD was shown to be higher than normal in 66% of cases (p less than 0.01). No correlation was evidenced between PD values and manometric alterations of the upper esophageal sphincter. On this basis, such alterations should not be related to possible mucosal injuries, as suggested by several authors, but most likely to a reflected or primary phenomenon, common to that causing the gastroesophageal reflux.
Esophagitis, Peptic↗
Accelerated onset of pancuronium with divided doses.
To determine the consequences of administering neuromuscular relaxants in divided doses, pancuronium was given either in a single dose, 0.07 mg X kg-1, or in an initial dose of 0.007 mg X kg-1 followed three minutes later with 0.063 mg X kg-1. When the drug was administered in divided dosage the onset time was reduced, the block was more intense and its duration of action was prolonged. It is suggested that such changes may be advantageous in the provision of rapid intense paralysis.
Anesthesia, General↗
End-tidal carbon dioxide tension and temperature changes after coronary artery bypass surgery.
Variations in end-tidal carbon dioxide partial pressure (PETCO2) and temperature were measured for six hours following coronary artery bypass surgery in twenty patients. In the recovery room, the patients were mechanically ventilated with a tidal volume of 12 ml X kg-1. Arterial blood gases were drawn every two hours, and the respiratory frequency was adjusted to maintain arterial carbon dioxide pressure (PaCO2) in the range of 30-45 mmHg. Naso-pharyngeal temperature was recorded every 30 minutes, and PETCO2 was measured continuously. The mean difference between temperature-corrected arterial and end-tidal CO2 pressure measurements was 3.2 mmHg (SD = 2.8; r = 0.963). This difference did not vary with time, temperature or PCO2. The largest temperature increases (mean 1.7 degree C/hour) occurred at a mean of 253 minutes after the end of surgery. End-tidal PCO2 increased markedly as temperature rose, in spite of a coincident increase in ventilation and then decreased as temperature stabilized. Large increases in CO2 production, caused by the metabolic demands during rewarming, most likely account for these changes. It is concluded that end-tidal CO2 recordings are reliable, and can help in maintaining normocarbia during the short but unstable period associated with rewarming following cardiac surgery.
Aged↗
Attempted acceleration of the onset of action of pancuronium. Effects of divided doses in infants and children.
The study was designed to determine whether the onset of action of pancuronium in infants and children could be accelerated by its administration in divided doses. Sixty paediatric patients (0-1 yr (n = 20); 1-3 yr (n = 20); 3-10 yr (n = 20)) were studied during nitrous oxide-oxygen-halothane anaesthesia using train-of-four stimulation, and the results were compared with data obtained previously in adults. The time to onset correlated with the patient's age, and an additional, small acceleration was produced following divided doses which did not alter the duration or pattern of neuromuscular blockade. It was concluded that, in children, divided doses of pancuronium are unlikely to offer important clinical advantages.
Anesthesia, Inhalation↗
The potencies of edrophonium and neostigmine as antagonists of pancuronium.
Dose response curves were constructed for edrophonium and neostigmine when used to antagonise pancuronium, 0.07 mg/kg during thiopentone-nitrous oxide-halothane anaesthesia. The antagonist was given when 10% twitch height had been restored and the effect was measured 10 minutes later. Recoveries to 50% and 90% twitch height were achieved with 167 and 828 micrograms/kg of edrophonium, and 10.5 and 51 micrograms/kg of neostigmine. The dose response curves were parallel and neostigmine was 16 times more potent than edrophonium. Combinations of equipotent doses of edrophonium and neostigmine were also administered and produced additive but not synergistic effects. It is concluded that either edrophonium or neostigmine may be used for the reversal of pancuronium neuromuscular blockade, but the combination of the two offers no advantage.
Adolescent↗
Antagonism of phase II succinylcholine block by neostigmine.
The neuromuscular effect of neostigmine, 1.25 mg/70 kg, was assessed in 40 adult patients 10 min after cessation of a succinylcholine infusion. The patients had received a thiopental-nitrous oxide anesthetic supplemented by halothane or fentanyl during which they were given at least 5 mg/kg succinylcholine over more than 90 min. Train-of-four monitoring was used. Neostigmine accelerated recovery of neuromuscular function in all patients. The degree of recovery was directly related to the train-of-four ratio, and the results in patients who had received halothane were no different from those who had received fentanyl. The findings are compatible with the hypothesis that phase I block depends upon the presence of circulating succinylcholine and decreases as the latter is cleared, whereas phase II block decreases more slowly. Thus succinylcholine block can be antagonized by neostigmine if enough time is allowed for phase I block to disappear and for a pure phase II block to be present.
Adult↗
Neuromuscular blocking drugs in anaesthesia.
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4-Aminopyridine↗
Vecuronium in renal failure.
Neuromuscular blockade during surgery was provided with vecuronium in 24 adult patients in end-stage renal failure and in 21 normal patients who served as controls. Dose response curves were constructed which showed that the effective doses required to produce 50, 90 and 95 per cent neuromuscular blockade in patients with renal failure were 27.5, 43 and 49 micrograms X kg-1 respectively. These were not significantly different from the doses of 31, 49 and 57 micrograms X kg-1 in the normal patients. Repeated small doses of 0.01 mg X kg-1 had a significantly longer duration of action and were associated with some cumulation in the renal failure group. Recovery from the block occurred rapidly after neostigmine, was no different in renal failure and was not associated with recurarization. It is concluded that, when given to subjects in renal failure, vecuronium offers advantages over established agents such as shorter duration of action and easy reversibility.
Adult↗
Differential effects of myoneural blocking drugs on neuromuscular transmission in infants.
Equipotent, paralysing doses of pancuronium and tubocurarine were administered to 40 patients, aged from 1 day to 12 months, during nitrous oxide, oxygen and fentanyl anaesthesia. Neuromuscular activity was measured during onset and recovery from paralysis using train-of-four stimulation. At the same depression of the first stimulus of the train, the train-of-four ratio was decreased more during recovery than during onset with each drug and more with tubocurarine than with pancuronium. These results are qualitatively similar to those found in adults, but the decrease in train-of-four ratio was less in infants. Thus, it is concluded that prejunctional neuromuscular activity, recognized as fade in response to train-of-four stimulation, can be detected after administration of pancuronium or tubocurarine to infants, but that it is less marked than in adults.
Anesthesia, General↗
Muscle electromechanical correlations during succinylcholine infusion.
The study was designed to compare the electromyographic (EMG) and evoked twitch tension (TT) responses in humans to train-of-four stimulation during neuromuscular blockade induced with a continuous succinylcholine infusion. Mean values of TT correlated well with EMG (r greater than 0.97), but several consistent discrepancies were noted. After the infusion was started but before the block was established, TT increased by up to 38%, which was accompanied by changes in the EMG signal indicative of repetitive activity. After stopping the infusion, TT but not EMG recovered to values greater than control, without changes in the shape of the EMG signal during the period of observation. This TT augmentation during recovery is consistent with a change in the contractile properties of muscle. Detection of phase II block was similar with EMG and TT (38.2 vs 41.3 min). Clinically, EMG and TT may be used interchangeably to evaluate neuromuscular blockade. In the research setting, the synchronous recording of both may help in understanding the mechanism of action of muscle relaxant drugs.
Adult↗
Succinylcholine apnoea: attempted reversal with anticholinesterases.
Anticholinesterases were administered in an attempt to antagonize prolonged neuromuscular blockade following the administration of succinylcholine in a patient later found to be homozygous for atypical plasma cholinesterase. Edrophonium 10 mg, given 74 min after succinylcholine, when train-of-four stimulation was characteristic of phase II block, produced partial antagonism which was not sustained. Repeated doses of edrophonium to 70 mg and neostigmine to 2.5 mg did not antagonize or augment the block. Spontaneous respiration recommenced 200 min after succinylcholine administration. It is concluded that anticholinesterases are only partially effective in restoring neuromuscular function in succinylcholine apnoea despite muscle twitch activity typical of phase II block.
Adult↗
Anticholinesterase antagonism of succinylcholine phase II block.
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Cholinesterase Inhibitors↗
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.
Adult↗
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.
Adult↗