- Email: [email protected]
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY LIVERPOOL MEETING
Br. J. Anaesth. (1981), 53, 663P
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY LIVERPOOL MEETING MARCH 28, 1981 ANXIETY IN DAY SURGERY PATIENTS Department ofPostgraduate Mtdicnu, University of Kult G. CLARK, D. ERWIN, P. YATE, D. BURT A N D E . MAJOR
A questionnaire survey of anxiety in day-surgery patients was conducted to determine their suitability for a trial of new shortacting benzodiazepines for premedication. Patients were invited to mark a 100-mm horizontal line between the limits of "calm" and "terrified" to describe best how they felt about the operation at that moment. Coindden tally and independently, a nurse rated the patient's anxiety as absent, slight, moderate or marked. Anxiety was assessed on admission, in the anaesthetic room and on discharge. When leaving the unit the patients were asked if they would have liked a tflblet before the operation to "ease their nerves". One hundred and eighteen patients (age 17-80 yr) admitted consecutively to the day surgery unit were studied. There were 65 female and S3 male patients. Sixty-five operations were performed under local, and S3 under general anaesthesia. Ninetyone patients had experienced anaesthesia and surgery previously. For premedication, 23 patients were given atropine 0.6 mg i.m. and another 13 patients received atropine with penicillin i.m. Six patients were prescribed oral antacid and three oral diazepam 20 mg. Although five anaesthetists participated in the study, one person administered the majority (3S/S3) of the general anaesthetics. Operations included general (58), oral (22), gynaecological (19), orthopaedic (12) and urological (7) surgery. The frequency of patient self-rating anxiety scores described a multimodal distribution with a marked skew towards the lower limit labelled "calm". Median values on the 100-mm scale were 22.0 on admen km, 24.5 in the anaesthetic room and 4.7 on discharge. These reflected mild to moderate levels of anxiety in the period before operation, which receded in most patients after operation. Analysis of variance produced «igntfinint differences between group means for sex, type of anaesthesia and previous fi|ifii>mf Male patients described significantly less anxiety in the anaesthetic room than female patients (P<0.001). Those patients who had surgery under local anaesthesia recorded significantly higher scores than those after general anaesthesia (P=0.015). The nurse's rating of patient anxiety gave a poor correlation with the patient's self-rating score, but was better when anxiety was absent. The frequency of changes in the anxiety score between the anaesthetic room and on admission showed a normal distribution, but that between discharge and the anaesthetic room was again multimodal. Only 17 of the 115 patients would have liked a tablet before operation to "ease their nerves". The anxiety scores of these patients did not differ significantly from those who did not eipiess this wish. We conclude that the variable characteristics of this population of day surgery patients, the ambivalance to anxtolytk oral premedication and the generally low levels of anxiety documented, do not offer favourable conditions for a trial of oral benzodiazepines for premedication.
A naesthttics Unit, Thi London Hospital In elderly patients undergoing minor surgery the postoperative drowsiness produced by many premedicant drtigs is disadvantageous. The relatively short half-life of temazepam (a benzodiazepine used commonly as a hypnotic) may render it suitable for premedication (Beechey, Eltringham and Studd, 1981). A double-blind double-dummy technique was uJjed to compare temazepam 20 mg (A), diazepam 10 mg (B) and placebo (C)in98 men aged 50-80yr who were allocated randomly to the three groups. Premedication was administered orally 60 min before the planned surgery. Assessments of efficacy of premedication were made (a) by an observer who scored the degree of sedation, (b) by the patient who scored a multiple affect adjective check list (MAACL) (Zuckerman, 1960), (c) by the anaesthetist (not a member of the study team) who marked a visual analogue scale. Anaesthesia comprised Althesin, fentanyl and nitrous oxide 66% in oxygen. Recovery was attested using a visuo-motor co-ordination test (Hendry et al., 1963) and any complication after operation was noted. The patients were asked for thenopinions of the premedication. Groups A, B and C were of comparable age and weight, and the duration of anaesthesia was 18.3, 18.7, 17.2 min respectively. The MAACL scores showed no difference either between groups or before and after premedication. The baseline observer scores were comparable in each group, but 1 h after premedication group A patients were significantly more sedated than group B (P<0.05). At 30 min significantly more patients were asleep after temazepam than after diazepam ( f <0.05), but there was no significant difference in observer scores. Both groups A and B were significantly more sedated than placebo at 30 min and 1 h CP<0.001 and i»<0.05). However, no differences between the groups were detected, immediately before induction of anaesthesia. The anaesthetist's visual analogue scores confirmed this finHing Mean time from end of surgery to obeying commands was significantly shorter in the placebo group (5.24± 1.32 min) than in the temazepam group (11.25±1.12 min; J><0.005) or diazepam group (8.71 ±1.16 min; J»<0.05), although the mean doses of Althesin and fentanyl were «i™i1«r in each group. Where the premedication—induction interval was 50-100 min, reaction times 1 h after waking were significantly prolonged compared with those before premedication. At 2 h the performance of the diazepam group was still significantly impaired (P<0.05) while both temazepam and placebo groups showed no significant difference from control values. More patients considered their premedication to have been good in the temazepam than in the diazepam group (P<0.05) or in the placebo group (P= 0.001).
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C.G.MALE
COMPARISON OF TEMAZEPAM, DIAZEPAM AND PLACEBO FOR PREMEDICATION IN MINOR UROLOGICAL SURGERY
BRITISH JOURNAL OF ANAESTHESIA
664P After operation 10% of patients in groups A and B complained of nausea, compared with 3% of group C. The combination of marked sedation before operation, minimal drowsiness after operation and good patient acceptability suggests that temazepam may be a useful premedicant, especially in the elderly.
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REFERENCES
Beechey, A. P. G., Eltringham, R. J., and Studd, C. (1981). Anaesthesia, 36,10. Hendry, J. G. B. et al. (1963). Br. J. Anaeslk., 35, 716. Zuckennan, M. (1960). / . Consult. Clm. Psych., 24,457.
I
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Q. i> if)
J.A.Ross Division of A natsthesia, Clinical Research Centre, Harrow A. J. SHEARER
Department of A naesthesia, Ninewells Hospital, Dundee H. J.MANSON
5-
1 ATA
35 ATA
1 ATA
35 ATA
1 ATA
35 ATA
Department of Anaesthesia, Memorial University, St Johns, Newfoundland Pressure reversal of anaesthesia is now a well documented phenomenon. The clinical manifestation of the effect of a drug, however, is dependent not only on the mechanism of action, but also on the pharmacokinetics. Although metabolism of the drugs tested seems not to be altered at pressure (Halsey, Wardley-Smith and Green, 1978) there is evidence that haemodynamics (Matsuda et al., 1978) and protein binding (Miller and Wilson, 1978) may be changed. The plasma half-life may be altered such that, although potency is reduced, duration of action after a single dose is increased. To examine this possibility we have studied the duration of action of a single i. v. dose of Althesin, methoheiitone and ketamine. Each agent was examined using groups of 20 mice of similar weight and strain, 10 of which were used as controls at atmospheric pressure (1 ATA). Each mouse was placed in turn in a Perspex drum and a vein cannulated in its tail, by which it was lightly restrained. Test animals were compressed with helium to 35 ATA at a rate of 9ATAmin~'. A premeasured dose of anaesthetic was administered, the cnnniila disconnected and the time to recovery measured. Recovery time was taken as the start of the first 10-s period over which the mouse remained upright, all four paws co-ordinating, with the drum rotating at 32revmin~'. In comparison with the control groups the duration of action at 35 ATA was reduced significantly (fig. 1) for Althesin (P<0.05) for ketamine and methohexitone (P<0.01). In the methohexitone group at pressure there was an increased frequency of convulsions, suggesting an interaction with the high pressure neurological syndrome at this depth.
Althesin
Ketamine
1.5 (jlrtre g" 1
50pgg- 1
7. diff 9.75
%drff 16.77
Methohex. 30pgg' 1 Xdiff 34.94
FIG. 1. Mean (±1 SD) of sleep times after a single i.v. injection of each agent.
INCREASE IN INTRAGASTRIC pH AFTER CIMETIDINE AND RANITIDINE J. R. JOHNSTON, W. MCCAUGHEY.P. J. WRIGHT, J. A. S. GAMBLE AND J. W. DUNDEE
Department of Anaesthetics, TheQueen's University of Belfast
In order to reduce the morbidity and mortality associated with aspiration of gastric contents, it is generally regarded as desirable to increase the pH of gastric contents before induction of anaesthesia. Although alkalis are most widely used for this purpose they mix poorly with gastric contents and have a short duration of effect. Cimetidine is very effective in increasing intragastric pH Qohnston et al., 1981), but it is also relatively short-acting. A newer antagonist, ranitidine, is four to nine times more potent than cimetidine (Daly, Humphrey and Stables, 1980) and this study was undertaken to compare their effectiveness at inhibiting acid secretion after i.v. and oral administration in patients underREFERENCES Halsey, M. J., Wardley-Smith, B., and Green, C. J. (1978). Br. J. going elective surgery. Patients were allocated randomly to one of six treatment groups Anaesth., SO, 1091. Matsuda, M., Nakayama, H., Itch, A., Kurata, F. K., Strauss, comprising placebo, ranitidine 80 mg i.v., cimetidine 400 mg i.v., or placebo, ranititiinr 150 mg orally or cimetidine 400mg R.H.,andHong,S.K. (1975). UnderseaBiomed. Res.,2,101. Miller, K. W., and Wilson, M. W. (1978). Anesthesiology, 48, orally. These were given at a specified time and the gastric contents withdrawn using a double-lumen (Salem) tube, after the 104.
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DURATION OF ACTION OF A SINGLE DOSE OF ALTHESIN, KETAMINE AND METHOHEXTTONE AT PRESSURE
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PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY
REFERENCES
Daly, M. J., Humphrey, J. M., and Stables, R. (1980). Gut, 21, 408. Johnston, J. R., McCaughey, W., Moore, J., and Dundee, J. W. (1981). Anaesthesia, (in press).
Pulmonary function was assessed again 24 and 48 h after operation in all patients and also on the 5th day in patients who had undergone chokcystectomy. Subjective assessment of pain, sedation, nausea and dizzincts was obtained at the same intervals using linear analogue scoring. There was no significant difference in any group between the mean age, height or weight, or the sex or smoking habits of patients receiving the different analgesics. In each group, changes in pulmonary function and linear analogue pain scores during the postoperative period were of the same magnitude irrespective of the analgesic used. Patients undergoing cholecystectomy who received buprenorphine had significantly greater sedation and nausea scores on the 1st day after operation than those receiving pethidine and greater sedation scores on the 2nd day than those receiving morphine. This study suggests that self-administration of i.v. pethidine is no more effective in relief of postoperative pain than morphine administered in the conventional manner Buprenorphine was found to have no major disadvantages when compared with morphine, but as it is not a Controlled Drug, has a long duration of action and may be administered sublingually, it offers significant advantages in terms of ease of administration. REFERENCES
Chakravarry, K., Tucker, W., Rosen, M., and Vickers, M. D.
(1979). Br. Med.J.,2,895.
COMPARISON OF I.M. MORPHINE, SUBLINGUAL BUPRENORPHINE, AND SELF-ADMINISTERED I.V. PETHIDINE FOR PAIN RELIEF AFTER OPERATION
Fry, E. N. S. (1979). Anaesthesia, 34, 549.
R. ELLIS, D. HA IN ES, R. SHAH, B. COTTON, A. R. AITICENHEAD AND G. SMITH
ISOLATED FOREARM TECHNIQUE FOR DETECTION OF WAKEFULNESS DURING GENERAL ANAESTHESIA
University Department of A naesthesia, Leicester The disadvantages of conventional treatment of postoperative pain are well recognized. Chakravarty and colleagues (1979) demonstrated that selfadministration of pethidine i.v. produced safe and effective pain relief following abdominal surgery, but did not compare its efficacy with an i.m. analgesic. Buprenorphine, a long acting analgesic which may be °Hmin«tered by the sublingual route, and is not a Controlled Drug, has been shown to be as effective as i.m. papaveretum in relieving postoperative pain as assessed by nurse observers using a fourpoint pain scoring system (Fry, 1979). The purpose of the present study was to compare by subjective and objective assessment the effects of sublingual buprenorphine 6-hourly, pethidine self-administered i.v. by a Cardiff paUiator, or i.m. morphine administered on demand following upper or lower abdominal surgery. Three groups of patients were studied. Forty-four patients undergoing chokcystectomy (group A) were allocated randomly to receive, in the period after operation, morphine i.m. on ArnnnH, pethidine via the Cardiff palliator, or sublingual buprenorphine, and to receive the same drug i.v. during operation. Morphine or buprenorphine was given to 36 patients undergoing inguinal hcrniorrhaphy (group B). Forty-seven patients undergoing abdominal hysterectomy (group C) received either morphine or pethidine. Assessment of static and dynamic pulmonary function was performed before operation in all patients. Oral diazepam 10-20 mg was administered 1 h before operation and a nitrous oxide in oiygeu anaesthetic technique with neuromuscular blockade was used.
J. BRECKENRIDGEANDA.R. AmCENHEAD
University Department of Anaesthesia, Leicester The risk of awaieuess during general anaesthesia has received considerable attention, particularly since the advent of techniques using neuromuscular blocking drugs. The use of the isolated forearm technique to detect a response to verbal commands was reported by Tunstall (1977), who suggested that a positive response in patients undergoing Caesarean section indicates a very light plane of general anaesthesia, and is a more accurate predictor of impending awareness than standard clinical signs. More widespread use of this technique as "an objective confirmation of wakefulness" has been suggested (Editorial, 1981). The purpose of the present study was to investigate the validity of the isolated forearm technique in the detection of light planes of anaesthesia in premedkated patients undergoing general surgical procedures. Twenty-four patients presenting for elective abdominal surgery gave informed consent to this study. Premedication comprised papaveretum 0.3 mgkg"1 i.m. 1 h before anaesthesia. Immediately before induction of anaesthesia, a pneumatic tourniquet on the upper right arm was inflated to 300 mm Hg, and a rubber bulb connected to a pressure transducer was placed in the palm of the right hand. A verbal message was relayed from a tape recorder through headphones placed over the ears, instructing the patient to squeeze the bulb when an electronic signal was heard. The signal and the pressure produced by compression of the bulb were displayed on a chart recorder. Anaesthesia was induced with thiopentone 4 mg kg"1 and fentanyl 1.5|igkg~' i.v. and muscle relaxation produced using
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establishment of endotracheal anaesthesia. The time was varied so that the drug administration to gastric aspiration interval decreased within one of seven hourly time intervals. The volume of contents was noted and pH measured using a Corning 113 pH meter. The mean pH and number of aspirates with pH less than 2.5 were noted for each of the seven time intervals. Compared with placebo, both drugs produced significant increases in intragastricpH when given i.v. 1-6 h before operation. However, the number of aspirates with a pH less than 2.5 was zero with both drugs given 1-3 h before operation. When administered orally, cimetidine 400 mg consistently increased gastric content pH to greater than 2.S only when given 2 - 3 h before operation. In the doses used, ranitidine produced this effect when given 2—7 h before operation. This difference between the two drugs may be a consequence of the doses used. Volumes of gastric contents were reduced consistently by both drugs compared with placebo.
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REFERENCES
Tunstall, M. E. (1977). BT. Med. / . , 1,1321. Editorial (1981). BT. J. Anaesth., 53,1.
IDENTIFICATION OF THE MODEL IN THE CONTROL OF NEUROMUSCULAR BLOCKADE USING PRBS TESTING
under open-loop conditions with the PRBS signal superimposed on the steady drug infusion. A PRBS sequence length of 128 changes with an interval of 33.3 s was used initially, while later tests used an interval of. 100.0 s. The resulting perturbations in the level of blockade as measured by the evoked e.m.g. were recorded on magnetic tape for analysis by a system identification package (SPAID). The identification of the underlying model has given results which were not predictable from estimates based on the large step responses. First, the estimated delay between infusion of drug and its effect on the neuromuscular junction is smaller than had been expected, being 1-2 min. Second, the dynamic response after the delay period cannot be approximated to a single exponential function, since the identification package could not produce a good fit to the experimental data using such a model. Third, the estimated time constants in the dynamics are 7"1 —1-4 min and 7"2= 12-40 min, in contrast to step response expectation of a single time constant of the order of 10 min. It is concluded that PRBS testing is a suitable means of identifying the dynamics involved in neuromuscular blockade, giving better results than step tests and providing information which is directly relevant to the design of good feedback controllers. REFERENCES
Asbury, A. J., Brown, B. H., and Linkens, D. A. (1980). Br. J. Anaesth.,S
D . A. LlNKENS AND S. J. RlMMEK
Department of Control Engineering, University ofShtffteld A. J. ASBURY
Department of Anaesthesia, University of Sheffield B.H. BROWN
Department of Medical Physics and Clinical Engineering, Hallamshire Hospital, Sheffield
COMPARISON OF THE EFFECTS ON HEART RATE AND ARTERIAL PRESSURE OF PANCURONIUM AND ORG NC45 IN ANAESTHETIZED MAN P. K. BARNES AND G. BRTNDLE-SMITH
The automatic feedback control of neuromuscular blockade using an infusion of pancuronium bromide has been reported recently (Asbury, Brown and Linkens, 1980). In these studies blockade was measured using the eypked e.m.g. and steady regulation was achieved in patients undergoing routine anaesthesia. The feedback controller was designed originally from information derived from open-loop step tests. To improve the controller further it is necessary to identify the underlying model ("the dynamics") more accurately. The injection of large doses of blocking drugs such as pancuronium 4 mg kg"' is not appropriate as the changes in blockade may move into non-linear response regions, while smaller bolus doses may produce changes which are indistinguishable from noise. Pseudo-Random Binary Sequence (PRBS) Testing, which is used widely in industry, is a more appropriate technique for system identification. The PRBS forces the system through a series of step rhangr*, such that the mean level of response stays well within the best operating region of the system. PRBS testing has been attempted in humans, but it was found that, as the human has a slow response to changes in blockade (particularly recovery), very long PRBS sequences were necessary to identify the system, and the physiological stability of the patient could not be guaranteed. Experiments were performed in the anaesthetized dog (metbohexitone, fentanyl and droperidol) to gain this information and the results are presented. Before the PRBS tests were performed steady neuromuscular blockade was established using the controller set to give 80% blockade. When the system was steady it was allowed to run
Department of Anaesthetics, Westminster Hospital, London Org NC 45, a monoquaternary analogue of pancuronium, is a potent neuromuscular blocking drug that appears to be devoid of antimuscarinic activity in neuromuscular blocking doses (Durant et al., 1979). It has been shown to produce less inhibition of the reuptake of noradrenaline at sympathetic nerve endings in the isolated perfused rat heart (Salt, Barnes and Conway, 1980). We have investigated the effects on bean rate and arterial pressure of equipotent doses of Org NC 45 and pancuronium in anaesthetized man. Healthy adults gave informed consent to the study. Premedication comprised diazepam orally, 1 h before induction of anaesthesia. On arrival in the anaestjjefic room a 22-gauge Teflon rnnrw)a was inserted unflfT local anaesthesia into a radial artery. After induction of anaesthesia with thiopentone 5 mg kg"1 subjects breathed nitrous oxide 70% in oxygen via a face-mask for 5 min. A bolus of either pancuronium 0.1 mg kg' 1 (11 patients) or Org NC45 0.12 mg kg' 1 (12 patients) was administered and the effects on bean rate and arterial pressure noted for 5 min. When spontaneous ventilation ceased, controlled ventilation was instituted via a face-mask. At the end of 5 min, thiopentone 1.5mgkg~' was administered, endotracheal intubation performed and the effect on arterial pressure recorded. Org NC45 had little effect on heart rate or mean arterial pressure after a bolus dose. In contrast, pancuronium produced a modest increase in heart rate, but had little effect on mean arterial pressure. Following endotracheal intubation, an increase in mean
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alcuronium 0.3 ing kg '. The lungs were ventilated with 66% nitrous oxide in oxygen. The response to the taped message was tested every 5 min for 20 min. The tourniquet was then removed. Standard questions to elicit recall of events during anaesthesia were put to the patients 24 h later. No patient responded to the verbal instructions during anaesthesia, and none recalled events or remembered dreaming. Eight patients demonstrated clinical signs of light anamthrftia following endotracheal intubation. Surgery proved impossible while the tourniquet remained inflated because of purposeful movement of the arm. While this communication is intended as a preliminary report, the results in the first 24 patients suggest that the isolated forearm technique is impracticable for use in patients undergoing general surgical procedures, and that it is less sensitive in the detection of light planes of general anaesthesia than standard clinical signs.
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY arterial pressure was observed in all patients, but this was more marked following pancuronium. The results observed indicate that Org NC 45 does not produce the vagolytic effect seen with pancuronium. Neither drug has an effect on arterial pressure if no stimulation is taking place. In the face of a sympathetic stimulus the increase in arterial pressure is greater following pancuronium than after Org NC 45. REFERENCES
the basis of these findings, it is recommended that glycopyrrolate be given in combination with neostigmine for antagonism of neuromuscular block. REFERENCES
Cozanitis, D. A., Dundee, J. W., Merrett, J. D., Jones, C. J., and Mirakhur, R. K. (1980). Br. J. Anaesth., 52,85. Mirakhur, R. K., Dundee, J. W., and Clarke, R. S. J. (1977). Br. J. Anaesth., A9, 825.
EFFECT OF NITROUS OXIDE ON THE ADAPTATION TO INSPIRATORY RESISTIVE LOADING IN MAN D. ROYSTON, C. JORDAN AND J. G. JONES
GLYCOPYRROLATE GIVEN BEFORE OR WITH NEOSTIGMINE FOR REVERSAL OF RESIDUAL NEUROMUSCULAR BLOCK C.J.JONES
A. H. Robots Co. Ltd, Horsham, West Sussex R. K. MmAKHmiAHD J. W. DUNDEE
Department of Anaesthetics, Quern's University of Belfast Gtycopyrrolate in a mixture with neostigmine has been evaluated extensively for the antagonism of residual neuromuscuUr block (Mirakhur, Dundee and Clarke, 1977; Cozanitis et al., 1980). Little information exists on the intrinsic effect of this agent on heart rate in anaesthetized patients or on the optimal dose and sequence for its use with antagonism of neuromuscular block. These were iramJTwH in the present study. Gtycopyrrolate 5, 10 or 15|igkg~' was administered either 6 min before or simultaneously with neostigmine 50 |ig kg' 1 to reverse the residual effects of pancuronium given to patients who had undergone elective operations. The patients were ASA grade 1 and there were 20 patients in each of the six groups. The effect of each regimen on heart rate and oropharyngeal secretions was assessed. Heart rate data were analysed using a linear modelling method. TABLE I. Maximum increase in heart rate (mean± SEM) and number of patients requiring additional gtycopyrrolate Glycopyrrolate
Before neostigmine 5 10 15 With neostigmine 5 10 15
Maximum increase in heart rate (%)
No. requiring additional drug
12±2.7 24±3.1 34 ±4.2
9 2 0
6±2.1 6±1.6 7±2.4
9 1 0
When administered before neostigmine, glycopyrrolate produced a dose-related increase in heart rate, but in combination, the drugs produced minimi! rhangr* in heart rate (table I). The ^rnflP'*«> doses administered by each method did not protect against the muscarinic effects of neostigmine and further doses were required. However, the two largest doses were adequate. On
Division of Anaesthesia, Clinical Research Centre, Harrow Nitrous oxide does not depress the ventilatory response to carbon dioxide (Eckenhoff and Hdrich, 1958), but there are no reports on the effect of nitrous oxide on the response to loaded breathing. We have studied the effect of nitrous oxide on loaded breathing because these two types of test may produce dissociated results (Jordan et al., 1979) and because of the clinical «igmfv-mv-^ of impaired adaptation to loaded breathing. Fight healthy male volunteers gave informed consent for this study, which was approved by the Hospital Ethical Committee. Each subject breathed in a supine position through a heated pneumotachograph which was attached to a non-rebreathing valve. Periodically, a linear inspiratory mtjitranrf (3.63 kPa litre"1 s' 1 ) was applied silently and without the subject's knowledge during an expiration. The times of inspiration (7"i) and expiration (7"B) were derived automatically by electronic analysis of the flow signal and were recorded continuously. Tidal volume was monitored with an inductance plethysmograph and end-tidal carbon dioxide ( P E ' C O 2 ) was measured by a mass spectrometer. The rate of respiration and minute volume were calculated subsequently. Following a period of familiarization, the subject breathed through the experimental apparatus for 15 min without the load and for a further 10 min after the application of the load. This procedure was repeated while the subjects breathed a gas mixture containing 20% nitrous oxide and then 40% nitrous oxide. At TABLE I. Changes produced (mean± SEM) in response to loading for V T , 7] and PE'CO, with the three gas mixtures ( A - load minus non-load). Differences between A values obtained while breathing nitrous oxide were compared with A values breathing airusngthepairedttestCP<0.05,"P<0.01) Inspired gas Air "First breath on load" response ATi(s) 2.4 ±0.95 AVr(litre) 0.3 ±0.2 Steady state response A7Ks) 1.2 ±0.3 A VT (litre) 0.04 ±0.05 'CO! (kPa) 0.00410.08
20% N 2 O
1.2 ±0.5 -0.06±0.13
40% N 2 O
0.9 ±0.5 * -0.08±0.17*
1.4 ±0.4 1.2 ±0.3 0.02 ±0.08 -0.06 ±0.05 0.17±0.06 0.4110.1"
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Durant, N. N., Marshall, I. G., Savege, D., Nelson, D. J., Sleigh, T., and Carlyle, I. C. (1979). / . Pharm. Pharmacol., 31, 831. Salt, P. J., Barnes, P. K., and Conway, C. M. (1980). Br. J. Anaesth., 52,313.
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668P least 20 min were allowed for equilibration with each concentration of nitrous oxide before the load was applied. Care was taken to ensure that the subjects weTe awake throughout the study. Mean values obtained during the last 2 min of the unloaded period were compared with measurements made after application of the load. The "first breath on load" response and the steady state response (mean of last 2 min on load) were determined. The results indicate that 40% nitrous oxide produced a significant change in the first breath on load response for VT and Tj (table I). However, in the steady state there was no significant change in VT or 7*i, but there was a highly significant increase in PE'CO2 w ' t n *W° nitrous oxide.
EFFECT OF GENERAL ANAESTHESIA ON PROPRANOLOL UPTAKE BY DOG LUNGS T. R. WILLIAMS, J. P. BLACKBURN, J. A. PANG AND D. GEDDES
REFERENCES
Dollery, C. T., and Junod, A. F. (1976). Br. J. PharmacoL, 57, 67. Pang, J. A., Blackburn, J. P., Butland, R. J. A.,and Geddes, D. M. (1980a). Br.]. Pharmacol.,70,114P. Corrin, B., Williams, T. R., and Geddes, D. M. (1980b). Clm. Sri., 59,13P.
EFFECTS OF OXPRENOLOL ON MYOCARDIAL FUNCTION DURING ENFLURANE ANAESTHESIA M.
G. R. CUTFIELD, C M . L.A.JONES
FRANCIS, P. FOEX, W. A. RYDER AND
Department ofClinical Measurement, Westminster Hospital and Department of Medicine, Brompton Hospital
Nuffield Department ofAnaesthetics, The Radclifft Infirmary, Oxford
Propraoolol is taken up by the lungs, probably by the vascular endothelium, following i.v. administration (Dollery and Junod, 1976). The uptake in conscious dogs is largely uninfluenced by the dose of drug given, cardiac output or pulmonary artery pressure. Blockade of one pulmonary artery produces a significant decrease in propranolol uptake (Pang et al., 1980 a, b). The effects of general anaesthesia on uptake of propranolol by the lung have been studied by two methods: (1) Uptake was measured by comparing the ratio of I4Cpropranolol 0.2 mg to indocyanine green 1.875 mg injected into the right atrium with the ratio of their concentrations in aortic blood collected over the duration of the first-pass dye outflow curve. Results have been expressed as the percentage of the injected dose of propranolol taken up by the lung during a single passage through the pulmonary circulation. (2) Uptake was measured also by collecting arterial blood samples at 1-s intervals following injection of a mixture of MCpropranolol and indocyanine green into the right atrium. Concentrations of propranolol and green dye were measured in each sample. Uptake of propranolol by the lung was calculated from the ratio of the areas of the washout curves (normalized with respect to the injected doses of dye and propranolol). Measurements based on single samples (method 1) showed that uptake of propranolol increased from 45%±4% (mean±SD) under control conditions to 88%+5% when anaesthesia was maintained with methohexitone and spontaneous ventilation breathing air; 89%±2% with methohexitone and IPPV (air) and 84%±2% when the animal was ventilated with halothane 1% in air. The differences in uptake between each anaesthetic technique and the control were significant (P<0.001). Multiple samples were taken (method 2) under control conditions, when uptake was 6%±6%. This increased to 43%±13% (P<0.01) when the animal was anaesthetized with methohexitone, spontaneous respiration. Single sample measurements over-estimate uptake of propranolol unless washout of drug and dye are synchronous; while
We have shown previously that oiprenolol protects regional myocardial function in the combined presence of myocardial ischaemia and enflurane anaesthesia (Cutfield et al., 1981). The present study was designed to see if oxprenolol exerted this beneficial effect primarily upon myocardium depressed by enflurane anaesthesia or primarily upon the ischaemic myocardium. Six dogs, premedicated with morphine O.Smgkg' 1 , were anaesthetized and the cardiovascular response to steadily deepening levels of enflurane anaesthesia with controlled ventilation was studied, both before and after the administration of oxprenolol. Regional myocardial function was measured in two segments of left ventricular wall with anatomically different coronary arterial supply using miniature ultrasonic length transducers implanted at sub-endocardial level in the myocardium. Concomitantly, measurements of left ventricular performance were made. The first phase of the technique consisted of stepped dose intervals of 0.25 MAC, from enflurane 0.5 to 1.5 MAC. Measurements were made after 10 min at each dose. After 20 min at 0.5 MAC, for recovery, oxprenolol 0.3 mgkg"1 was administered i.v. and similar measurements were recorded continuously for 10 min. The third phase was identical to the first phase and began 10 min after injection of oxprenolol. As in previously reported studies (Horanetal., 1977; Cutfield et al., 1980, 1981), significant dose-related reductions were observed in both global and regional function of the left ventricle in response to enflurane anaesthesia. These changes were of the same magnitude as those observed in earlier studies. Mean arterial pressure and cardiac output were reduced to 60% of control over the stated dose range, whilst left ventricular stroke work and peak power decreased to 40%. There was no net change in heart rate. Left anterior descending coronary blood flow was reduced to 75% and regional function, expressed as total systolic shortening, was depressed equally in both segments. No significant acute changes were recorded in any of the observed variables in response to the i.v. injection of oxprenolol 0.3 mgkg"' at steady state enflurane 0.5 MAC anaesthesia.
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REFERENCES
Eckenhoff, J. E.,and Hdrich, M. (\95i). Anesthesiology, 19,240. Jordan, C.,Lehane,J.R.,Robson,P.J.,and Jones, J.G. (1979). Br.J.Anaesth., 51,497.
multiple sample measurements underestimate uptake because the dye curve is inadequately sampled and its area is consequently underestimated. Although there are differences in lung uptake of propranolol when measured by single and multiple sample methods, there is no doubt that general anaesthesia causes a large increase in uptake which may be related to the high lipid solubility of both propranolol and the anaesthetic agents used in this study.
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY The effects of repeating the same stepwise increase of enflurane dosage following oxpreoolol administration were compared with the first phase. There were no «ignif*-am differences from the pre-ozprenolol dose-response data in any of the variable* measured and derived. These results suggest that, after i.v. injection of ozpTenolol 0.3mgkg~' there is no acute haemodynamic interaction with enflurane anaesthesia at 0.5 MAC in this model. Furthermore, prior administration of oxprenolol in this dose does not modify the depressant action of enflurane on global or regional left ventricular performance.
REFERENCES
Cutfield, G. R., Francis, C M . , Foex, P., Lowenstein, E., Davies, W. L., and Ryder, W. A. (1980). Br. J. Anaesth., 52, 951P. (1981). Br. J. Amuuh., 53, 189P. Horan,B. F., Prys-Roberts.C, Hamilton, W. K., and Roberts, J. G. (1977). Br. J. Amusth., 49,1189.
DEVELOPMENT AND APPLICATION OF MICROPROCESSOR ANALYSIS OF THE E.E.G. IN HUMAN ANAESTHESIA J. S. H. CURNOW, J. H. W. BALLANCE A N D C . PRYS-ROBERTS
Dtpartmtnts ofMtdical Physics and Anatsthtsia, Unwtrsityof Bristol Measurement of the e.e.g. has proved useful in the assessment of varying levels of anaesthesia. The use of processed e.e.g., in the form of Compressed Spectral Arrays (CAS), in operating theatres was pioneered by Bickford's group in the early 1970s. These first systems were based on a main-line computer system, and were very expensive to implement (Bickford, Fleming and Billinger, 1971). A semi-portable device was described which was peripheral to a main-frame computer (Myers et al., 1973), but this required the main-frame computer to be available. A small, cheap, dedicated electronic system also has been described by the same group, but this did not have the flexibility of the computerbased system. The system we have been developing is microprocessor-based, and originally used a Fast Walsh Transform (FWT) technique. The use of Walsh Transforms to analyse e.e.g. had already been validated (Weide, Andres and Ianone, 1978), and they were well suited to a microprocessor system, as no multiplications were required. However, recent advances in microprocessor peripheral chip technology have allowed a return to Fast Fourier Transform (FFT) techniques. The system will analyse 10-s epochs of data from two channels of e.e.g. data, and display in real-time spectral information in the frequency range 1-15 Hz for each channel. The system embodies the cheapness of a dedicated electronic system with the flexibility of a main-frame computer system. In addition to developing a dedicated microprocessor system,
we have also utilized a Digital Equipment Corporation MINC computer system based on the LSI-11 microcomputer, which is tailored specifically to work on analog inputs, and outputs, and to perform signal processing routines. An e.e.g. analysis program was written in BASIC and was thus fairly slow to run. Froma 10-s epoch of e.e.g. data a 256-point power spectrum was calculated, and the spectrum was normalized to the maximum power value. The display used at present shows the value of the maximum power as the length of a line on the left hand side of the display. A Bistable-modulated Spectral Array (BS A) of the range 1 -15 Hz is displayed, showing the positions in the spectrum v.here the power was greater than 10% of the maximum. The display on the right is a standard Compressed Spectral Array (CSA), normalized to ma-rimnm power, over the frequency range 1-15 Hz. The Bistable-modulated Spectral Array has been tried as a method of data reduction to allow easier visualization of any trends in the frequency spectrum of the e.e.g. This e.e.g. analysis system has been used to investigate the responses of eight patients in whom anaesthesia has been induced with ICI 35 868, a new i.v. anaesthetic. The e.e.g. analysts was continued during maintenance anaesthesia with an infusion of ICI 35 868 (51.3 + 3.8 SEM |ig kg"' min' 1 ) used to supplement nitrous oxide 67% in oxygen in these patients, and correlated with the mean whole blood concentrations of ICI 35 868 of 1.54 ±0.22 SEM (ig ml"' during the steady-state infusion. Induction of anaesthesia was associated with a shift of the power/frequency spectrum to a predominant pattern of high amplitude, low frequency (1-3 Hz) waves and a loss of high frequency activity (8-12 Hz). During maintenance infusions the e.e.g. spectrum was restored to high amplitude activity in the 1-3 Hz and 8-12 Hz bands. REFERENCES
Bkkford, R. G., Fleming, N. I., and Billinger, T. W. (1971). EUctrotnceph. Clm. Nturophysiol., 31,632. Myers, R.,R., Stockard, J. S., Fleming,N. I., France,C. J., and Bickford, R. G. (1973). Proc. San Diego Btomtd. Sympos., 12, 17. Weide, B. W., Andres, L. T., and Ianone, A. M. (1978). Real-time analysis of EEG using Walsh Transforms. Compui. Biol. M*d., 8,255.
SOME ANTHROPOMETRIC ASPECTS OF MALIGNANT HYPERPYREXIA SUSCEPTIBILITY I. T. CAMPBELL AND M. ST J. HOGGE
Royal L werpool Hospital, L iverpool F. R. ELLIS AND P. J. HALSALL
Stjamts's Hospital, Le*ds The widespread occurrence of the porcine stress syndrome is thought to be a result of selective breeding to produce carcasses of a high muscle to fat ratio (William*, 1977). Humans susceptible to malignant hyperpyrexia (MHS) tend to have a greater muscle bulk than the general population (Britt, Kwong and Endrenyi, 1977). In particular, localized enlargement of the muscles of the lateral aspect of the thigh has been observed frequently in MHS patients and pro bands. This has been referred to as the Evans myopathy, after the family first described by Denborough. No systematic anthropometric study appears to have been made on human MHS subjects. The present work was undertaken to
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ACKNOWLEDGEMENTS
G. R. CutfieJd is in receipt of an Overseas Research Fellowship from the Medical Research Council of New Zealand. C. M. Francis is in receipt of a Medical Research Council Studentship.
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MH is twice as common in males as in females. This study suggests that MHS males have less fat than a comparable normal population, but their lean body mass is no larger. This difference in percentage fat is not seen in MHS females. Likewise, MHS f^mali*« have larger thigh* than normal fcmwlrt—a difference not seen in the males, although it is not possible from these data to say how much of the thigh is fat and how much is muscle. These results suggest that there may be a relationship, in humans, between MH susceptibility and the relative quantities and distribution in the body of active metabolic tissue (fat-free mass) and its energy store (body fat), but that this relationship varies between the sexes.
REFERENCES
Britt, B. A., Kwong, F. H., and Endrenyi, L. (1977). In Malignant Hyperthtrmia: Current Concepts (ed. Ernest O. Henschel), p. 9. New York: Appleton-Century-Crofts. Durnin, J. V. G. A., and Womersley, J. (1974). Br. J. Nutr., 32, 77. Williams, C. H. (1977). In Malignant Hyptrthtrmia: Current Conctpa (ed. Ernest O. Henschel), p. 117. New York: Apple ton-Century-Crofts.
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determine if there is any quantitative difference between MHS subjects and controls in the relationship between fat and muscle, and if there is any consistent difference in the shape of the thigh. Height, weight and skinfold thicknesses (Durain and Womersley, 1974) were measured in 82 patients who had been referred for muscle biopsy to determine their susceptibility to malignant hyperpyrexia (MH). Forty-three (27 male) were positive on biopsy and 39 negative (21 male). There was no statistically significant difference between the MHS and normal subjects of the same sex with respect to age, height or weight. Percentage body fat was calculated from skinfold thickness (Dumin and Womersley, 1974) and in the MHS males was 16.7%. This was significantly less than 21.3% in the normal subjects (P<0.02). There was no difference in fat-free mass between the two groups. In the female subjects there was no difference in percentage body fat between MHS and normal individuals. In a further study six comparable coronal diameters of the left thigh of 92 patients referred for biopsy were measured from A-P photographs. Forty-three were MHS (24 men) and 49 normal (29 men). There was no significant difference between the male groups, but in the females the coronal diameters of the upper half of the thigh were significantly larger in the MHS group than in the controls (P<0.01).
BRITISH JOURNAL OF ANAESTHESIA
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY LIVERPOOL MEETING MARCH 28, 1981 ANXIETY IN DAY SURGERY PATIENTS Department ofPostgraduate Mtdicnu, University of Kult G. CLARK, D. ERWIN, P. YATE, D. BURT A N D E . MAJOR
A questionnaire survey of anxiety in day-surgery patients was conducted to determine their suitability for a trial of new shortacting benzodiazepines for premedication. Patients were invited to mark a 100-mm horizontal line between the limits of "calm" and "terrified" to describe best how they felt about the operation at that moment. Coindden tally and independently, a nurse rated the patient's anxiety as absent, slight, moderate or marked. Anxiety was assessed on admission, in the anaesthetic room and on discharge. When leaving the unit the patients were asked if they would have liked a tflblet before the operation to "ease their nerves". One hundred and eighteen patients (age 17-80 yr) admitted consecutively to the day surgery unit were studied. There were 65 female and S3 male patients. Sixty-five operations were performed under local, and S3 under general anaesthesia. Ninetyone patients had experienced anaesthesia and surgery previously. For premedication, 23 patients were given atropine 0.6 mg i.m. and another 13 patients received atropine with penicillin i.m. Six patients were prescribed oral antacid and three oral diazepam 20 mg. Although five anaesthetists participated in the study, one person administered the majority (3S/S3) of the general anaesthetics. Operations included general (58), oral (22), gynaecological (19), orthopaedic (12) and urological (7) surgery. The frequency of patient self-rating anxiety scores described a multimodal distribution with a marked skew towards the lower limit labelled "calm". Median values on the 100-mm scale were 22.0 on admen km, 24.5 in the anaesthetic room and 4.7 on discharge. These reflected mild to moderate levels of anxiety in the period before operation, which receded in most patients after operation. Analysis of variance produced «igntfinint differences between group means for sex, type of anaesthesia and previous fi|ifii>mf Male patients described significantly less anxiety in the anaesthetic room than female patients (P<0.001). Those patients who had surgery under local anaesthesia recorded significantly higher scores than those after general anaesthesia (P=0.015). The nurse's rating of patient anxiety gave a poor correlation with the patient's self-rating score, but was better when anxiety was absent. The frequency of changes in the anxiety score between the anaesthetic room and on admission showed a normal distribution, but that between discharge and the anaesthetic room was again multimodal. Only 17 of the 115 patients would have liked a tablet before operation to "ease their nerves". The anxiety scores of these patients did not differ significantly from those who did not eipiess this wish. We conclude that the variable characteristics of this population of day surgery patients, the ambivalance to anxtolytk oral premedication and the generally low levels of anxiety documented, do not offer favourable conditions for a trial of oral benzodiazepines for premedication.
A naesthttics Unit, Thi London Hospital In elderly patients undergoing minor surgery the postoperative drowsiness produced by many premedicant drtigs is disadvantageous. The relatively short half-life of temazepam (a benzodiazepine used commonly as a hypnotic) may render it suitable for premedication (Beechey, Eltringham and Studd, 1981). A double-blind double-dummy technique was uJjed to compare temazepam 20 mg (A), diazepam 10 mg (B) and placebo (C)in98 men aged 50-80yr who were allocated randomly to the three groups. Premedication was administered orally 60 min before the planned surgery. Assessments of efficacy of premedication were made (a) by an observer who scored the degree of sedation, (b) by the patient who scored a multiple affect adjective check list (MAACL) (Zuckerman, 1960), (c) by the anaesthetist (not a member of the study team) who marked a visual analogue scale. Anaesthesia comprised Althesin, fentanyl and nitrous oxide 66% in oxygen. Recovery was attested using a visuo-motor co-ordination test (Hendry et al., 1963) and any complication after operation was noted. The patients were asked for thenopinions of the premedication. Groups A, B and C were of comparable age and weight, and the duration of anaesthesia was 18.3, 18.7, 17.2 min respectively. The MAACL scores showed no difference either between groups or before and after premedication. The baseline observer scores were comparable in each group, but 1 h after premedication group A patients were significantly more sedated than group B (P<0.05). At 30 min significantly more patients were asleep after temazepam than after diazepam ( f <0.05), but there was no significant difference in observer scores. Both groups A and B were significantly more sedated than placebo at 30 min and 1 h CP<0.001 and i»<0.05). However, no differences between the groups were detected, immediately before induction of anaesthesia. The anaesthetist's visual analogue scores confirmed this finHing Mean time from end of surgery to obeying commands was significantly shorter in the placebo group (5.24± 1.32 min) than in the temazepam group (11.25±1.12 min; J><0.005) or diazepam group (8.71 ±1.16 min; J»<0.05), although the mean doses of Althesin and fentanyl were «i™i1«r in each group. Where the premedication—induction interval was 50-100 min, reaction times 1 h after waking were significantly prolonged compared with those before premedication. At 2 h the performance of the diazepam group was still significantly impaired (P<0.05) while both temazepam and placebo groups showed no significant difference from control values. More patients considered their premedication to have been good in the temazepam than in the diazepam group (P<0.05) or in the placebo group (P= 0.001).
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C.G.MALE
COMPARISON OF TEMAZEPAM, DIAZEPAM AND PLACEBO FOR PREMEDICATION IN MINOR UROLOGICAL SURGERY
BRITISH JOURNAL OF ANAESTHESIA
664P After operation 10% of patients in groups A and B complained of nausea, compared with 3% of group C. The combination of marked sedation before operation, minimal drowsiness after operation and good patient acceptability suggests that temazepam may be a useful premedicant, especially in the elderly.
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REFERENCES
Beechey, A. P. G., Eltringham, R. J., and Studd, C. (1981). Anaesthesia, 36,10. Hendry, J. G. B. et al. (1963). Br. J. Anaeslk., 35, 716. Zuckennan, M. (1960). / . Consult. Clm. Psych., 24,457.
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J.A.Ross Division of A natsthesia, Clinical Research Centre, Harrow A. J. SHEARER
Department of A naesthesia, Ninewells Hospital, Dundee H. J.MANSON
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1 ATA
35 ATA
1 ATA
35 ATA
1 ATA
35 ATA
Department of Anaesthesia, Memorial University, St Johns, Newfoundland Pressure reversal of anaesthesia is now a well documented phenomenon. The clinical manifestation of the effect of a drug, however, is dependent not only on the mechanism of action, but also on the pharmacokinetics. Although metabolism of the drugs tested seems not to be altered at pressure (Halsey, Wardley-Smith and Green, 1978) there is evidence that haemodynamics (Matsuda et al., 1978) and protein binding (Miller and Wilson, 1978) may be changed. The plasma half-life may be altered such that, although potency is reduced, duration of action after a single dose is increased. To examine this possibility we have studied the duration of action of a single i. v. dose of Althesin, methoheiitone and ketamine. Each agent was examined using groups of 20 mice of similar weight and strain, 10 of which were used as controls at atmospheric pressure (1 ATA). Each mouse was placed in turn in a Perspex drum and a vein cannulated in its tail, by which it was lightly restrained. Test animals were compressed with helium to 35 ATA at a rate of 9ATAmin~'. A premeasured dose of anaesthetic was administered, the cnnniila disconnected and the time to recovery measured. Recovery time was taken as the start of the first 10-s period over which the mouse remained upright, all four paws co-ordinating, with the drum rotating at 32revmin~'. In comparison with the control groups the duration of action at 35 ATA was reduced significantly (fig. 1) for Althesin (P<0.05) for ketamine and methohexitone (P<0.01). In the methohexitone group at pressure there was an increased frequency of convulsions, suggesting an interaction with the high pressure neurological syndrome at this depth.
Althesin
Ketamine
1.5 (jlrtre g" 1
50pgg- 1
7. diff 9.75
%drff 16.77
Methohex. 30pgg' 1 Xdiff 34.94
FIG. 1. Mean (±1 SD) of sleep times after a single i.v. injection of each agent.
INCREASE IN INTRAGASTRIC pH AFTER CIMETIDINE AND RANITIDINE J. R. JOHNSTON, W. MCCAUGHEY.P. J. WRIGHT, J. A. S. GAMBLE AND J. W. DUNDEE
Department of Anaesthetics, TheQueen's University of Belfast
In order to reduce the morbidity and mortality associated with aspiration of gastric contents, it is generally regarded as desirable to increase the pH of gastric contents before induction of anaesthesia. Although alkalis are most widely used for this purpose they mix poorly with gastric contents and have a short duration of effect. Cimetidine is very effective in increasing intragastric pH Qohnston et al., 1981), but it is also relatively short-acting. A newer antagonist, ranitidine, is four to nine times more potent than cimetidine (Daly, Humphrey and Stables, 1980) and this study was undertaken to compare their effectiveness at inhibiting acid secretion after i.v. and oral administration in patients underREFERENCES Halsey, M. J., Wardley-Smith, B., and Green, C. J. (1978). Br. J. going elective surgery. Patients were allocated randomly to one of six treatment groups Anaesth., SO, 1091. Matsuda, M., Nakayama, H., Itch, A., Kurata, F. K., Strauss, comprising placebo, ranitidine 80 mg i.v., cimetidine 400 mg i.v., or placebo, ranititiinr 150 mg orally or cimetidine 400mg R.H.,andHong,S.K. (1975). UnderseaBiomed. Res.,2,101. Miller, K. W., and Wilson, M. W. (1978). Anesthesiology, 48, orally. These were given at a specified time and the gastric contents withdrawn using a double-lumen (Salem) tube, after the 104.
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DURATION OF ACTION OF A SINGLE DOSE OF ALTHESIN, KETAMINE AND METHOHEXTTONE AT PRESSURE
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PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY
REFERENCES
Daly, M. J., Humphrey, J. M., and Stables, R. (1980). Gut, 21, 408. Johnston, J. R., McCaughey, W., Moore, J., and Dundee, J. W. (1981). Anaesthesia, (in press).
Pulmonary function was assessed again 24 and 48 h after operation in all patients and also on the 5th day in patients who had undergone chokcystectomy. Subjective assessment of pain, sedation, nausea and dizzincts was obtained at the same intervals using linear analogue scoring. There was no significant difference in any group between the mean age, height or weight, or the sex or smoking habits of patients receiving the different analgesics. In each group, changes in pulmonary function and linear analogue pain scores during the postoperative period were of the same magnitude irrespective of the analgesic used. Patients undergoing cholecystectomy who received buprenorphine had significantly greater sedation and nausea scores on the 1st day after operation than those receiving pethidine and greater sedation scores on the 2nd day than those receiving morphine. This study suggests that self-administration of i.v. pethidine is no more effective in relief of postoperative pain than morphine administered in the conventional manner Buprenorphine was found to have no major disadvantages when compared with morphine, but as it is not a Controlled Drug, has a long duration of action and may be administered sublingually, it offers significant advantages in terms of ease of administration. REFERENCES
Chakravarry, K., Tucker, W., Rosen, M., and Vickers, M. D.
(1979). Br. Med.J.,2,895.
COMPARISON OF I.M. MORPHINE, SUBLINGUAL BUPRENORPHINE, AND SELF-ADMINISTERED I.V. PETHIDINE FOR PAIN RELIEF AFTER OPERATION
Fry, E. N. S. (1979). Anaesthesia, 34, 549.
R. ELLIS, D. HA IN ES, R. SHAH, B. COTTON, A. R. AITICENHEAD AND G. SMITH
ISOLATED FOREARM TECHNIQUE FOR DETECTION OF WAKEFULNESS DURING GENERAL ANAESTHESIA
University Department of A naesthesia, Leicester The disadvantages of conventional treatment of postoperative pain are well recognized. Chakravarty and colleagues (1979) demonstrated that selfadministration of pethidine i.v. produced safe and effective pain relief following abdominal surgery, but did not compare its efficacy with an i.m. analgesic. Buprenorphine, a long acting analgesic which may be °Hmin«tered by the sublingual route, and is not a Controlled Drug, has been shown to be as effective as i.m. papaveretum in relieving postoperative pain as assessed by nurse observers using a fourpoint pain scoring system (Fry, 1979). The purpose of the present study was to compare by subjective and objective assessment the effects of sublingual buprenorphine 6-hourly, pethidine self-administered i.v. by a Cardiff paUiator, or i.m. morphine administered on demand following upper or lower abdominal surgery. Three groups of patients were studied. Forty-four patients undergoing chokcystectomy (group A) were allocated randomly to receive, in the period after operation, morphine i.m. on ArnnnH, pethidine via the Cardiff palliator, or sublingual buprenorphine, and to receive the same drug i.v. during operation. Morphine or buprenorphine was given to 36 patients undergoing inguinal hcrniorrhaphy (group B). Forty-seven patients undergoing abdominal hysterectomy (group C) received either morphine or pethidine. Assessment of static and dynamic pulmonary function was performed before operation in all patients. Oral diazepam 10-20 mg was administered 1 h before operation and a nitrous oxide in oiygeu anaesthetic technique with neuromuscular blockade was used.
J. BRECKENRIDGEANDA.R. AmCENHEAD
University Department of Anaesthesia, Leicester The risk of awaieuess during general anaesthesia has received considerable attention, particularly since the advent of techniques using neuromuscular blocking drugs. The use of the isolated forearm technique to detect a response to verbal commands was reported by Tunstall (1977), who suggested that a positive response in patients undergoing Caesarean section indicates a very light plane of general anaesthesia, and is a more accurate predictor of impending awareness than standard clinical signs. More widespread use of this technique as "an objective confirmation of wakefulness" has been suggested (Editorial, 1981). The purpose of the present study was to investigate the validity of the isolated forearm technique in the detection of light planes of anaesthesia in premedkated patients undergoing general surgical procedures. Twenty-four patients presenting for elective abdominal surgery gave informed consent to this study. Premedication comprised papaveretum 0.3 mgkg"1 i.m. 1 h before anaesthesia. Immediately before induction of anaesthesia, a pneumatic tourniquet on the upper right arm was inflated to 300 mm Hg, and a rubber bulb connected to a pressure transducer was placed in the palm of the right hand. A verbal message was relayed from a tape recorder through headphones placed over the ears, instructing the patient to squeeze the bulb when an electronic signal was heard. The signal and the pressure produced by compression of the bulb were displayed on a chart recorder. Anaesthesia was induced with thiopentone 4 mg kg"1 and fentanyl 1.5|igkg~' i.v. and muscle relaxation produced using
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establishment of endotracheal anaesthesia. The time was varied so that the drug administration to gastric aspiration interval decreased within one of seven hourly time intervals. The volume of contents was noted and pH measured using a Corning 113 pH meter. The mean pH and number of aspirates with pH less than 2.5 were noted for each of the seven time intervals. Compared with placebo, both drugs produced significant increases in intragastricpH when given i.v. 1-6 h before operation. However, the number of aspirates with a pH less than 2.5 was zero with both drugs given 1-3 h before operation. When administered orally, cimetidine 400 mg consistently increased gastric content pH to greater than 2.S only when given 2 - 3 h before operation. In the doses used, ranitidine produced this effect when given 2—7 h before operation. This difference between the two drugs may be a consequence of the doses used. Volumes of gastric contents were reduced consistently by both drugs compared with placebo.
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REFERENCES
Tunstall, M. E. (1977). BT. Med. / . , 1,1321. Editorial (1981). BT. J. Anaesth., 53,1.
IDENTIFICATION OF THE MODEL IN THE CONTROL OF NEUROMUSCULAR BLOCKADE USING PRBS TESTING
under open-loop conditions with the PRBS signal superimposed on the steady drug infusion. A PRBS sequence length of 128 changes with an interval of 33.3 s was used initially, while later tests used an interval of. 100.0 s. The resulting perturbations in the level of blockade as measured by the evoked e.m.g. were recorded on magnetic tape for analysis by a system identification package (SPAID). The identification of the underlying model has given results which were not predictable from estimates based on the large step responses. First, the estimated delay between infusion of drug and its effect on the neuromuscular junction is smaller than had been expected, being 1-2 min. Second, the dynamic response after the delay period cannot be approximated to a single exponential function, since the identification package could not produce a good fit to the experimental data using such a model. Third, the estimated time constants in the dynamics are 7"1 —1-4 min and 7"2= 12-40 min, in contrast to step response expectation of a single time constant of the order of 10 min. It is concluded that PRBS testing is a suitable means of identifying the dynamics involved in neuromuscular blockade, giving better results than step tests and providing information which is directly relevant to the design of good feedback controllers. REFERENCES
Asbury, A. J., Brown, B. H., and Linkens, D. A. (1980). Br. J. Anaesth.,S
D . A. LlNKENS AND S. J. RlMMEK
Department of Control Engineering, University ofShtffteld A. J. ASBURY
Department of Anaesthesia, University of Sheffield B.H. BROWN
Department of Medical Physics and Clinical Engineering, Hallamshire Hospital, Sheffield
COMPARISON OF THE EFFECTS ON HEART RATE AND ARTERIAL PRESSURE OF PANCURONIUM AND ORG NC45 IN ANAESTHETIZED MAN P. K. BARNES AND G. BRTNDLE-SMITH
The automatic feedback control of neuromuscular blockade using an infusion of pancuronium bromide has been reported recently (Asbury, Brown and Linkens, 1980). In these studies blockade was measured using the eypked e.m.g. and steady regulation was achieved in patients undergoing routine anaesthesia. The feedback controller was designed originally from information derived from open-loop step tests. To improve the controller further it is necessary to identify the underlying model ("the dynamics") more accurately. The injection of large doses of blocking drugs such as pancuronium 4 mg kg"' is not appropriate as the changes in blockade may move into non-linear response regions, while smaller bolus doses may produce changes which are indistinguishable from noise. Pseudo-Random Binary Sequence (PRBS) Testing, which is used widely in industry, is a more appropriate technique for system identification. The PRBS forces the system through a series of step rhangr*, such that the mean level of response stays well within the best operating region of the system. PRBS testing has been attempted in humans, but it was found that, as the human has a slow response to changes in blockade (particularly recovery), very long PRBS sequences were necessary to identify the system, and the physiological stability of the patient could not be guaranteed. Experiments were performed in the anaesthetized dog (metbohexitone, fentanyl and droperidol) to gain this information and the results are presented. Before the PRBS tests were performed steady neuromuscular blockade was established using the controller set to give 80% blockade. When the system was steady it was allowed to run
Department of Anaesthetics, Westminster Hospital, London Org NC 45, a monoquaternary analogue of pancuronium, is a potent neuromuscular blocking drug that appears to be devoid of antimuscarinic activity in neuromuscular blocking doses (Durant et al., 1979). It has been shown to produce less inhibition of the reuptake of noradrenaline at sympathetic nerve endings in the isolated perfused rat heart (Salt, Barnes and Conway, 1980). We have investigated the effects on bean rate and arterial pressure of equipotent doses of Org NC 45 and pancuronium in anaesthetized man. Healthy adults gave informed consent to the study. Premedication comprised diazepam orally, 1 h before induction of anaesthesia. On arrival in the anaestjjefic room a 22-gauge Teflon rnnrw)a was inserted unflfT local anaesthesia into a radial artery. After induction of anaesthesia with thiopentone 5 mg kg"1 subjects breathed nitrous oxide 70% in oxygen via a face-mask for 5 min. A bolus of either pancuronium 0.1 mg kg' 1 (11 patients) or Org NC45 0.12 mg kg' 1 (12 patients) was administered and the effects on bean rate and arterial pressure noted for 5 min. When spontaneous ventilation ceased, controlled ventilation was instituted via a face-mask. At the end of 5 min, thiopentone 1.5mgkg~' was administered, endotracheal intubation performed and the effect on arterial pressure recorded. Org NC45 had little effect on heart rate or mean arterial pressure after a bolus dose. In contrast, pancuronium produced a modest increase in heart rate, but had little effect on mean arterial pressure. Following endotracheal intubation, an increase in mean
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alcuronium 0.3 ing kg '. The lungs were ventilated with 66% nitrous oxide in oxygen. The response to the taped message was tested every 5 min for 20 min. The tourniquet was then removed. Standard questions to elicit recall of events during anaesthesia were put to the patients 24 h later. No patient responded to the verbal instructions during anaesthesia, and none recalled events or remembered dreaming. Eight patients demonstrated clinical signs of light anamthrftia following endotracheal intubation. Surgery proved impossible while the tourniquet remained inflated because of purposeful movement of the arm. While this communication is intended as a preliminary report, the results in the first 24 patients suggest that the isolated forearm technique is impracticable for use in patients undergoing general surgical procedures, and that it is less sensitive in the detection of light planes of general anaesthesia than standard clinical signs.
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY arterial pressure was observed in all patients, but this was more marked following pancuronium. The results observed indicate that Org NC 45 does not produce the vagolytic effect seen with pancuronium. Neither drug has an effect on arterial pressure if no stimulation is taking place. In the face of a sympathetic stimulus the increase in arterial pressure is greater following pancuronium than after Org NC 45. REFERENCES
the basis of these findings, it is recommended that glycopyrrolate be given in combination with neostigmine for antagonism of neuromuscular block. REFERENCES
Cozanitis, D. A., Dundee, J. W., Merrett, J. D., Jones, C. J., and Mirakhur, R. K. (1980). Br. J. Anaesth., 52,85. Mirakhur, R. K., Dundee, J. W., and Clarke, R. S. J. (1977). Br. J. Anaesth., A9, 825.
EFFECT OF NITROUS OXIDE ON THE ADAPTATION TO INSPIRATORY RESISTIVE LOADING IN MAN D. ROYSTON, C. JORDAN AND J. G. JONES
GLYCOPYRROLATE GIVEN BEFORE OR WITH NEOSTIGMINE FOR REVERSAL OF RESIDUAL NEUROMUSCULAR BLOCK C.J.JONES
A. H. Robots Co. Ltd, Horsham, West Sussex R. K. MmAKHmiAHD J. W. DUNDEE
Department of Anaesthetics, Quern's University of Belfast Gtycopyrrolate in a mixture with neostigmine has been evaluated extensively for the antagonism of residual neuromuscuUr block (Mirakhur, Dundee and Clarke, 1977; Cozanitis et al., 1980). Little information exists on the intrinsic effect of this agent on heart rate in anaesthetized patients or on the optimal dose and sequence for its use with antagonism of neuromuscular block. These were iramJTwH in the present study. Gtycopyrrolate 5, 10 or 15|igkg~' was administered either 6 min before or simultaneously with neostigmine 50 |ig kg' 1 to reverse the residual effects of pancuronium given to patients who had undergone elective operations. The patients were ASA grade 1 and there were 20 patients in each of the six groups. The effect of each regimen on heart rate and oropharyngeal secretions was assessed. Heart rate data were analysed using a linear modelling method. TABLE I. Maximum increase in heart rate (mean± SEM) and number of patients requiring additional gtycopyrrolate Glycopyrrolate
Before neostigmine 5 10 15 With neostigmine 5 10 15
Maximum increase in heart rate (%)
No. requiring additional drug
12±2.7 24±3.1 34 ±4.2
9 2 0
6±2.1 6±1.6 7±2.4
9 1 0
When administered before neostigmine, glycopyrrolate produced a dose-related increase in heart rate, but in combination, the drugs produced minimi! rhangr* in heart rate (table I). The ^rnflP'*«> doses administered by each method did not protect against the muscarinic effects of neostigmine and further doses were required. However, the two largest doses were adequate. On
Division of Anaesthesia, Clinical Research Centre, Harrow Nitrous oxide does not depress the ventilatory response to carbon dioxide (Eckenhoff and Hdrich, 1958), but there are no reports on the effect of nitrous oxide on the response to loaded breathing. We have studied the effect of nitrous oxide on loaded breathing because these two types of test may produce dissociated results (Jordan et al., 1979) and because of the clinical «igmfv-mv-^ of impaired adaptation to loaded breathing. Fight healthy male volunteers gave informed consent for this study, which was approved by the Hospital Ethical Committee. Each subject breathed in a supine position through a heated pneumotachograph which was attached to a non-rebreathing valve. Periodically, a linear inspiratory mtjitranrf (3.63 kPa litre"1 s' 1 ) was applied silently and without the subject's knowledge during an expiration. The times of inspiration (7"i) and expiration (7"B) were derived automatically by electronic analysis of the flow signal and were recorded continuously. Tidal volume was monitored with an inductance plethysmograph and end-tidal carbon dioxide ( P E ' C O 2 ) was measured by a mass spectrometer. The rate of respiration and minute volume were calculated subsequently. Following a period of familiarization, the subject breathed through the experimental apparatus for 15 min without the load and for a further 10 min after the application of the load. This procedure was repeated while the subjects breathed a gas mixture containing 20% nitrous oxide and then 40% nitrous oxide. At TABLE I. Changes produced (mean± SEM) in response to loading for V T , 7] and PE'CO, with the three gas mixtures ( A - load minus non-load). Differences between A values obtained while breathing nitrous oxide were compared with A values breathing airusngthepairedttestCP<0.05,"P<0.01) Inspired gas Air "First breath on load" response ATi(s) 2.4 ±0.95 AVr(litre) 0.3 ±0.2 Steady state response A7Ks) 1.2 ±0.3 A VT (litre) 0.04 ±0.05 'CO! (kPa) 0.00410.08
20% N 2 O
1.2 ±0.5 -0.06±0.13
40% N 2 O
0.9 ±0.5 * -0.08±0.17*
1.4 ±0.4 1.2 ±0.3 0.02 ±0.08 -0.06 ±0.05 0.17±0.06 0.4110.1"
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Durant, N. N., Marshall, I. G., Savege, D., Nelson, D. J., Sleigh, T., and Carlyle, I. C. (1979). / . Pharm. Pharmacol., 31, 831. Salt, P. J., Barnes, P. K., and Conway, C. M. (1980). Br. J. Anaesth., 52,313.
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668P least 20 min were allowed for equilibration with each concentration of nitrous oxide before the load was applied. Care was taken to ensure that the subjects weTe awake throughout the study. Mean values obtained during the last 2 min of the unloaded period were compared with measurements made after application of the load. The "first breath on load" response and the steady state response (mean of last 2 min on load) were determined. The results indicate that 40% nitrous oxide produced a significant change in the first breath on load response for VT and Tj (table I). However, in the steady state there was no significant change in VT or 7*i, but there was a highly significant increase in PE'CO2 w ' t n *W° nitrous oxide.
EFFECT OF GENERAL ANAESTHESIA ON PROPRANOLOL UPTAKE BY DOG LUNGS T. R. WILLIAMS, J. P. BLACKBURN, J. A. PANG AND D. GEDDES
REFERENCES
Dollery, C. T., and Junod, A. F. (1976). Br. J. PharmacoL, 57, 67. Pang, J. A., Blackburn, J. P., Butland, R. J. A.,and Geddes, D. M. (1980a). Br.]. Pharmacol.,70,114P. Corrin, B., Williams, T. R., and Geddes, D. M. (1980b). Clm. Sri., 59,13P.
EFFECTS OF OXPRENOLOL ON MYOCARDIAL FUNCTION DURING ENFLURANE ANAESTHESIA M.
G. R. CUTFIELD, C M . L.A.JONES
FRANCIS, P. FOEX, W. A. RYDER AND
Department ofClinical Measurement, Westminster Hospital and Department of Medicine, Brompton Hospital
Nuffield Department ofAnaesthetics, The Radclifft Infirmary, Oxford
Propraoolol is taken up by the lungs, probably by the vascular endothelium, following i.v. administration (Dollery and Junod, 1976). The uptake in conscious dogs is largely uninfluenced by the dose of drug given, cardiac output or pulmonary artery pressure. Blockade of one pulmonary artery produces a significant decrease in propranolol uptake (Pang et al., 1980 a, b). The effects of general anaesthesia on uptake of propranolol by the lung have been studied by two methods: (1) Uptake was measured by comparing the ratio of I4Cpropranolol 0.2 mg to indocyanine green 1.875 mg injected into the right atrium with the ratio of their concentrations in aortic blood collected over the duration of the first-pass dye outflow curve. Results have been expressed as the percentage of the injected dose of propranolol taken up by the lung during a single passage through the pulmonary circulation. (2) Uptake was measured also by collecting arterial blood samples at 1-s intervals following injection of a mixture of MCpropranolol and indocyanine green into the right atrium. Concentrations of propranolol and green dye were measured in each sample. Uptake of propranolol by the lung was calculated from the ratio of the areas of the washout curves (normalized with respect to the injected doses of dye and propranolol). Measurements based on single samples (method 1) showed that uptake of propranolol increased from 45%±4% (mean±SD) under control conditions to 88%+5% when anaesthesia was maintained with methohexitone and spontaneous ventilation breathing air; 89%±2% with methohexitone and IPPV (air) and 84%±2% when the animal was ventilated with halothane 1% in air. The differences in uptake between each anaesthetic technique and the control were significant (P<0.001). Multiple samples were taken (method 2) under control conditions, when uptake was 6%±6%. This increased to 43%±13% (P<0.01) when the animal was anaesthetized with methohexitone, spontaneous respiration. Single sample measurements over-estimate uptake of propranolol unless washout of drug and dye are synchronous; while
We have shown previously that oiprenolol protects regional myocardial function in the combined presence of myocardial ischaemia and enflurane anaesthesia (Cutfield et al., 1981). The present study was designed to see if oxprenolol exerted this beneficial effect primarily upon myocardium depressed by enflurane anaesthesia or primarily upon the ischaemic myocardium. Six dogs, premedicated with morphine O.Smgkg' 1 , were anaesthetized and the cardiovascular response to steadily deepening levels of enflurane anaesthesia with controlled ventilation was studied, both before and after the administration of oxprenolol. Regional myocardial function was measured in two segments of left ventricular wall with anatomically different coronary arterial supply using miniature ultrasonic length transducers implanted at sub-endocardial level in the myocardium. Concomitantly, measurements of left ventricular performance were made. The first phase of the technique consisted of stepped dose intervals of 0.25 MAC, from enflurane 0.5 to 1.5 MAC. Measurements were made after 10 min at each dose. After 20 min at 0.5 MAC, for recovery, oxprenolol 0.3 mgkg"1 was administered i.v. and similar measurements were recorded continuously for 10 min. The third phase was identical to the first phase and began 10 min after injection of oxprenolol. As in previously reported studies (Horanetal., 1977; Cutfield et al., 1980, 1981), significant dose-related reductions were observed in both global and regional function of the left ventricle in response to enflurane anaesthesia. These changes were of the same magnitude as those observed in earlier studies. Mean arterial pressure and cardiac output were reduced to 60% of control over the stated dose range, whilst left ventricular stroke work and peak power decreased to 40%. There was no net change in heart rate. Left anterior descending coronary blood flow was reduced to 75% and regional function, expressed as total systolic shortening, was depressed equally in both segments. No significant acute changes were recorded in any of the observed variables in response to the i.v. injection of oxprenolol 0.3 mgkg"' at steady state enflurane 0.5 MAC anaesthesia.
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REFERENCES
Eckenhoff, J. E.,and Hdrich, M. (\95i). Anesthesiology, 19,240. Jordan, C.,Lehane,J.R.,Robson,P.J.,and Jones, J.G. (1979). Br.J.Anaesth., 51,497.
multiple sample measurements underestimate uptake because the dye curve is inadequately sampled and its area is consequently underestimated. Although there are differences in lung uptake of propranolol when measured by single and multiple sample methods, there is no doubt that general anaesthesia causes a large increase in uptake which may be related to the high lipid solubility of both propranolol and the anaesthetic agents used in this study.
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY The effects of repeating the same stepwise increase of enflurane dosage following oxpreoolol administration were compared with the first phase. There were no «ignif*-am differences from the pre-ozprenolol dose-response data in any of the variable* measured and derived. These results suggest that, after i.v. injection of ozpTenolol 0.3mgkg~' there is no acute haemodynamic interaction with enflurane anaesthesia at 0.5 MAC in this model. Furthermore, prior administration of oxprenolol in this dose does not modify the depressant action of enflurane on global or regional left ventricular performance.
REFERENCES
Cutfield, G. R., Francis, C M . , Foex, P., Lowenstein, E., Davies, W. L., and Ryder, W. A. (1980). Br. J. Anaesth., 52, 951P. (1981). Br. J. Amuuh., 53, 189P. Horan,B. F., Prys-Roberts.C, Hamilton, W. K., and Roberts, J. G. (1977). Br. J. Amusth., 49,1189.
DEVELOPMENT AND APPLICATION OF MICROPROCESSOR ANALYSIS OF THE E.E.G. IN HUMAN ANAESTHESIA J. S. H. CURNOW, J. H. W. BALLANCE A N D C . PRYS-ROBERTS
Dtpartmtnts ofMtdical Physics and Anatsthtsia, Unwtrsityof Bristol Measurement of the e.e.g. has proved useful in the assessment of varying levels of anaesthesia. The use of processed e.e.g., in the form of Compressed Spectral Arrays (CAS), in operating theatres was pioneered by Bickford's group in the early 1970s. These first systems were based on a main-line computer system, and were very expensive to implement (Bickford, Fleming and Billinger, 1971). A semi-portable device was described which was peripheral to a main-frame computer (Myers et al., 1973), but this required the main-frame computer to be available. A small, cheap, dedicated electronic system also has been described by the same group, but this did not have the flexibility of the computerbased system. The system we have been developing is microprocessor-based, and originally used a Fast Walsh Transform (FWT) technique. The use of Walsh Transforms to analyse e.e.g. had already been validated (Weide, Andres and Ianone, 1978), and they were well suited to a microprocessor system, as no multiplications were required. However, recent advances in microprocessor peripheral chip technology have allowed a return to Fast Fourier Transform (FFT) techniques. The system will analyse 10-s epochs of data from two channels of e.e.g. data, and display in real-time spectral information in the frequency range 1-15 Hz for each channel. The system embodies the cheapness of a dedicated electronic system with the flexibility of a main-frame computer system. In addition to developing a dedicated microprocessor system,
we have also utilized a Digital Equipment Corporation MINC computer system based on the LSI-11 microcomputer, which is tailored specifically to work on analog inputs, and outputs, and to perform signal processing routines. An e.e.g. analysis program was written in BASIC and was thus fairly slow to run. Froma 10-s epoch of e.e.g. data a 256-point power spectrum was calculated, and the spectrum was normalized to the maximum power value. The display used at present shows the value of the maximum power as the length of a line on the left hand side of the display. A Bistable-modulated Spectral Array (BS A) of the range 1 -15 Hz is displayed, showing the positions in the spectrum v.here the power was greater than 10% of the maximum. The display on the right is a standard Compressed Spectral Array (CSA), normalized to ma-rimnm power, over the frequency range 1-15 Hz. The Bistable-modulated Spectral Array has been tried as a method of data reduction to allow easier visualization of any trends in the frequency spectrum of the e.e.g. This e.e.g. analysis system has been used to investigate the responses of eight patients in whom anaesthesia has been induced with ICI 35 868, a new i.v. anaesthetic. The e.e.g. analysts was continued during maintenance anaesthesia with an infusion of ICI 35 868 (51.3 + 3.8 SEM |ig kg"' min' 1 ) used to supplement nitrous oxide 67% in oxygen in these patients, and correlated with the mean whole blood concentrations of ICI 35 868 of 1.54 ±0.22 SEM (ig ml"' during the steady-state infusion. Induction of anaesthesia was associated with a shift of the power/frequency spectrum to a predominant pattern of high amplitude, low frequency (1-3 Hz) waves and a loss of high frequency activity (8-12 Hz). During maintenance infusions the e.e.g. spectrum was restored to high amplitude activity in the 1-3 Hz and 8-12 Hz bands. REFERENCES
Bkkford, R. G., Fleming, N. I., and Billinger, T. W. (1971). EUctrotnceph. Clm. Nturophysiol., 31,632. Myers, R.,R., Stockard, J. S., Fleming,N. I., France,C. J., and Bickford, R. G. (1973). Proc. San Diego Btomtd. Sympos., 12, 17. Weide, B. W., Andres, L. T., and Ianone, A. M. (1978). Real-time analysis of EEG using Walsh Transforms. Compui. Biol. M*d., 8,255.
SOME ANTHROPOMETRIC ASPECTS OF MALIGNANT HYPERPYREXIA SUSCEPTIBILITY I. T. CAMPBELL AND M. ST J. HOGGE
Royal L werpool Hospital, L iverpool F. R. ELLIS AND P. J. HALSALL
Stjamts's Hospital, Le*ds The widespread occurrence of the porcine stress syndrome is thought to be a result of selective breeding to produce carcasses of a high muscle to fat ratio (William*, 1977). Humans susceptible to malignant hyperpyrexia (MHS) tend to have a greater muscle bulk than the general population (Britt, Kwong and Endrenyi, 1977). In particular, localized enlargement of the muscles of the lateral aspect of the thigh has been observed frequently in MHS patients and pro bands. This has been referred to as the Evans myopathy, after the family first described by Denborough. No systematic anthropometric study appears to have been made on human MHS subjects. The present work was undertaken to
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ACKNOWLEDGEMENTS
G. R. CutfieJd is in receipt of an Overseas Research Fellowship from the Medical Research Council of New Zealand. C. M. Francis is in receipt of a Medical Research Council Studentship.
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MH is twice as common in males as in females. This study suggests that MHS males have less fat than a comparable normal population, but their lean body mass is no larger. This difference in percentage fat is not seen in MHS females. Likewise, MHS f^mali*« have larger thigh* than normal fcmwlrt—a difference not seen in the males, although it is not possible from these data to say how much of the thigh is fat and how much is muscle. These results suggest that there may be a relationship, in humans, between MH susceptibility and the relative quantities and distribution in the body of active metabolic tissue (fat-free mass) and its energy store (body fat), but that this relationship varies between the sexes.
REFERENCES
Britt, B. A., Kwong, F. H., and Endrenyi, L. (1977). In Malignant Hyperthtrmia: Current Concepts (ed. Ernest O. Henschel), p. 9. New York: Appleton-Century-Crofts. Durnin, J. V. G. A., and Womersley, J. (1974). Br. J. Nutr., 32, 77. Williams, C. H. (1977). In Malignant Hyptrthtrmia: Current Conctpa (ed. Ernest O. Henschel), p. 117. New York: Apple ton-Century-Crofts.
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determine if there is any quantitative difference between MHS subjects and controls in the relationship between fat and muscle, and if there is any consistent difference in the shape of the thigh. Height, weight and skinfold thicknesses (Durain and Womersley, 1974) were measured in 82 patients who had been referred for muscle biopsy to determine their susceptibility to malignant hyperpyrexia (MH). Forty-three (27 male) were positive on biopsy and 39 negative (21 male). There was no statistically significant difference between the MHS and normal subjects of the same sex with respect to age, height or weight. Percentage body fat was calculated from skinfold thickness (Dumin and Womersley, 1974) and in the MHS males was 16.7%. This was significantly less than 21.3% in the normal subjects (P<0.02). There was no difference in fat-free mass between the two groups. In the female subjects there was no difference in percentage body fat between MHS and normal individuals. In a further study six comparable coronal diameters of the left thigh of 92 patients referred for biopsy were measured from A-P photographs. Forty-three were MHS (24 men) and 49 normal (29 men). There was no significant difference between the male groups, but in the females the coronal diameters of the upper half of the thigh were significantly larger in the MHS group than in the controls (P<0.01).
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