Biomedical subjects
Publications and source records attributed to N J Harper.
The anaesthetic management of a patient whose giant cerebral aneurysm was clipped is described. Profound hypothermia and thiopentone were used to provide cerebral protection during circulatory arrest. Atracurium was used to provide muscle relaxation; the level of neuromuscular block and plasma concentrations of atracurium and laudanosine were measured.
In Britain it is traditional that each operating theatre has an adjacent anaesthetic room (1). The implications for equipping current theatre suites and the design of new theatres are wide-ranging. There are no data available on the attitudes of anaesthetists in this country towards the necessity for anaesthetic rooms and the extent of the anaesthetic equipment found in them. This survey in the North West region suggests that all consultant anaesthetists regard the availability of an anaesthetic room as a necessity, and most consider that the current level of vital-signs monitoring equipment in the anaesthetic room is inadequate.
The case is described of a patient with myasthenia gravis who required prolonged controlled ventilation for respiratory failure. Muscular relaxation was obtained with a continuous infusion of atracurium 5 mg h-1 for 45 h. Following cessation of the infusion, paralysis disappeared rapidly.
We have studied the influence of a reduced dose of neostigmine on recovery from vecuronium-induced neuromuscular block in 26 adult patients, using electromyographic responses to train-of-four (TOF) stimulation. Neostigmine 10, 20 or 40 micrograms kg-1 was administered when the first response had recovered spontaneously to 5-10% or 40-50% of control. Antagonism was accepted as adequate when the first response reached 90% of control and the TOF ratio reached 0.7. At both degrees of spontaneous recovery, neostigmine 40 micrograms kg-1 evoked the most rapid antagonism. Clinical recovery was satisfactory with no differences between groups. Block produced by neostigmine was not observed. The pattern of recovery of the single response and the TOF ratio was not altered by neostigmine in the range of doses studied. We suggest that the dose of neostigmine should not be reduced below 40 micrograms kg-1 even when all responses of the TOF are present.
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.
In a study which involved 120 adult patients, the ED95 of suxamethonium was shown to be 0.51 mg/kg, using an electromyographic technique. Marked individual variation in response was noted, for example a dose of 0.3 mg/kg produced a range of blockade from 4%-90%. Body surface area was shown to be more significantly related to blockade than lean body mass or total body weight.
An error in setting a syringe driver caused a 2.75 kg infant to receive 37 mg atracurium over 75 minutes. Clinically full recovery of muscle power had returned spontaneously 135 minutes after the infusion was stopped. The child suffered no ill effects. Assay of blood and urine for atracurium and laudanosine confirmed rapid clearance of the drug.
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A new test method is described for assessing the loss of prime in metered-dose aerosols. Two representative metered-dose valve designs and two storage positions were used to assess the utility of this test method at three different sites. Loss of prime, defined as a valve delivery 15% below the mean, was detected in three of the four test configurations. The first significant loss of prime in this study was observed at the two-week time point for valves without drain tanks stored in the upright position. Onset of loss of prime was shown to be dependent on valve design as well as storage position, thus alternate valves or storage conditions should yield different results. This test method appeared to be reproducible over the three test sites, with a slight variation in results attributed to differences in storage conditions and agitation during sample handling. This test method intentionally excluded agitation which is in sharp contrast to the normal "shake well before use" instruction to the patient. Following one priming actuation, all of the valves returned to their mean valve delivery.
The pattern of neuromuscular blockade in the first dorsal interosseous muscle (1st DI) and the adductor pollicis muscle was compared electromyographically following atracurium or vecuronium. There were no clinically significant differences between the muscles in respect of onset time, maximum blockade, train-of-four ratio, or recovery index. There were no problems in recording a consistent electromyogram from the 1st DI, which appears to be well suited to clinical monitoring.
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The effect of atracurium or vecuronium on the depolarization phase of the evoked compound action potential of the adductor pollicis has been investigated in 30 adult patients. Patients were studied using single supramaximal stimulation of the ulnar nerve at the wrist. The evoked compound action potential was measured over the adductor pollicis muscle. When blockade by atracurium exceeded 80%, a significant decrease in latency was recorded (P less than 0.05). There was no significant change in latency after vecuronium. During the onset of blockade, depression of the amplitude of the evoked compound action potential was associated with a prolongation of its duration (P less than 0.05). The mean maximum increase in the negative deflection time was found to be similar after atracurium and after vecuronium. However, this phase was prolonged to a greater extent for a given degree of amplitude depression during the onset of blockade by atracurium (P less than 0.05).
The effects of neuromuscular blockade by atracurium and vecuronium on the power spectrum of the evoked compound action potential (ECAP) of the adductor pollicis were investigated in 30 adult patients undergoing elective surgery. The changes in amplitude and mean power frequency (MPF) of the ECAP were measured. Ten patients received an ED95 (0.23 mg kg-1) of atracurium and 10 received an ED95 (0.055 mg kg-1) of vecuronium. The remaining 10 patients did not receive any neuromuscular blocking drug, and were monitored for 6 min to exclude any time-related changes in the ECAP. Neuromuscular blockade produced a decrease in total power and a shift towards lower frequencies. This was reflected in a decrease in the MPF in those patients receiving atracurium or vecuronium. There was no significant difference (P less than 0.05) between the atracurium and vecuronium groups in the magnitude of the change in MPF. These findings suggest that the previously reported increase in the duration of the negative deflection of the ECAP is predominantly the result of a change in its frequency components.
The effects of atracurium and alcuronium on the evoked mechanical and electromyographic responses of the adductor pollicis were investigated in 30 adult patients. The ulnar nerve was stimulated with trains of four supramaximal pulses of 0.2 ms duration and a frequency of 2 Hz at intervals of 20 s. The mechanical response was measured using a strain gauge force transducer and the evoked compound action potential (ECAP) was recorded simultaneously using a Medelec MS91 electromyography system. Depression of the electromyographic and mechanical responses, caused by atracurium, was similar during onset and antagonism of blockade. During onset of blockade by alcuronium, the mechanical response was depressed to a significantly greater extent compared with the ECAP. This difference was not observed during antagonism with neostigmine. The rates of onset of atracurium and alcuronium were generally similar, but the rate of onset of mechanical fade was greater in the alcuronium group. There was no significant quantitative difference between the rates of antagonism of alcuronium and atracurium when assessed by the mechanical first response ratio. Electromyographic first response and electromyographic and mechanical train-of-four ratios recovered more rapidly in the atracurium group. These findings suggest that the differences between mechanical and electromyographic measurements of neuromuscular blockade are drug-specific and are more pronounced during the onset of blockade than during its antagonism by neostigmine.
Eighty-seven patients undergoing routine laparoscopy were divided randomly into two groups to study the effect of nitrous oxide anaesthesia on the incidence of postoperative vomiting. Patients in group A received nitrous oxide as part of their anaesthetic, while in group B nitrous oxide was omitted. Significantly fewer patients in group B vomited when compared with group A (17 percent and 49 percent respectively; p less than 0.005). We suggest that an anaesthetic technique which avoids nitrous oxide may be especially indicated in patients undergoing laparoscopy.
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The sensitivities of two in-vitro preparations to neuromuscular blocking agents have been compared. The guinea-pig phrenic nerve diaphragm preparation proved to be more sensitive to vecuronium, atracurium and pancuronium than the equivalent preparation from the rat. Only tubocurarine had a similar potency on the preparations from both species. This would suggest that the guinea-pig diaphragm would be the most appropriate bioassay preparation if only small quantities of drug were available. Small differences in the cholinesterase content of the preparations was not thought to be a likely reason for the differences between the two preparations.
The neuromuscular blocking action of atracurium and vecuronium acting separately and in combination have been compared using the evoked EMG of the adductor pollicis muscle. Dose response curves have been drawn for the drugs given separately and found to be nonparallel (P less than 0.05). Atracurium was calculated to be 5.25 and 4.1 times less potent than vecuronium, ED50 and ED95 respectively. The effect on neuromuscular transmission of a combined medication using equipotent doses of atracurium and vecuronium, determined from the dose response plots, was found to be greater than would be expected by addition of their separate actions. The combination of small doses resulted in significant neuromuscular blockade.