Proceedings of the Anaesthetic Research Society

British Journal of Anaesthesia 1995; 75: 651P–665P

ABSTRACTS

Proceedings of the Anaesthetic Research Society SHEFFIELD MEETING July 7–8, 1995 (The name of the author presenting the paper is shown in bold type. * Indicates non-member.) All authors have certified that, where appropriate, studies have been conducted with the approval of the relevant Human Ethics Committee or Animal Experimental Review Committee.

Pharmacokinetics of 51W89 administered by constant infusion: a comparison with atracurium besylate C. E. SMITH*, M. M. VAN MIERT*, C. J. R. PARKER AND J. M. HUNTER University Department of Anaesthesia, Liverpool 51W89 (1R cis-1⬘R cis atracurium) is one of the 10 stereoisomers of atracurium [1]. The purpose of this study was to compare the pharmacokinetic profile of 51W89 with that of the three groups of isomers of atracurium besylate, when given by constant infusion. Twenty healthy patients scheduled for elective surgery were allocated randomly to receive 51W89 or atracurium. The patients were premedicated with diazepam 5–10 mg orally. Anaesthesia was induced with midazolam 0.05–0.1 mg kg
1, fentanyl 2–8
g kg
1 and thiopentone 4–8 mg kg
1 and maintained with nitrous oxide 66 % in oxygen. After induction of anaesthesia, neuromuscular monitoring was instituted using a mechanomyograph (Myograph) and the train-of-four (TOF) twitch technique. Once a steady-state baseline recording was obtained and a “blank” blood sample (5 ml) had been taken, the patients in group A received a bolus of 51W89 0.1 mg kg
1 (2
ED95) and patients in group B received atracurium 0.5 mg kg
1 into a fastflowing i.v. infusion. When the first twitch of the TOF (T1) had recovered to 5 %, an infusion of 51W89 3
g kg
1 min
1 was begun in patients in group A and an infusion of atracurium 10
g kg
1 min
1 in patients in group B. The infusion rates were adjusted at 3-min intervals, as necessary to maintain T1 at 5 % (SD 4 %). At the end of surgery, spontaneous recovery from neuromuscular block was allowed to occur. Blood samples were taken from a dedicated i.v. cannula at 2, 4, 6, 10, 20, 30, 45 and 60 min after the bolus dose until the start of the infusion, at 15min intervals during the infusion and at 2, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360 and 480 min after stopping the infusion. Each blood sample was added to a test-tube containing tripotassium EDTA. It was centrifuged immediately; 2 ml of plasma were then added to 8 ml of sulphuric acid 0.015 mol litre
1 and deep frozen. The plasma samples were analysed using high performance liquid chromatography with fluorescence detection. The coefficient of variation of the assay for 51W89 was 11.2 % and for atracurium, 11.3 %. The three groups of isomers of atracurium were assayed separately [2]. Pharmacokinetic analysis of the

plasma data was undertaken using the NONMEN program: a twocompartment model was fitted. The different isomer groups of atracurium had different pharmacokinetics with trans-trans having the greatest clearance and cis-cis the least (table 1). The clearance of 51W89 may be less than that of cis-cis atracurium and its elimination half-life was longer. Key words Neuromuscular block, 51W89. Neuromuscular block, atracurium. Pharmacokinetics, atracurium. Acknowledgement Th Wellcome Foundation provided the 51W89 and a grant towards this study. References 1. Lien CA, Schmith VD, Belmont MR, Kisor D, Savarese JJ. Anesthesiology 1994; 81: A1082. 2. Tsui D, Graham GG, Torda TA. Anesthesiology 1987; 67: 722–728. Effect of neuromuscular block on the shape of the evoked electromyogram D. C. SMITH AND C. R. SEAVELL* Department of Anaesthesia, Southampton General Hospital The duration and frequency spectrum of the evoked compound action potential (ECAP) change during onset of neuromuscular block with atracurium and vecuronium, but not significantly during induction of anaesthesia in patients who do not receive a neuromuscular blocking drug [1, 2]. We wanted to know whether the change in shape of the ECAP persisted beyond the induction period, and to investigate the correlation between the electromyographic (EMG) first (T1) response to train-of-four stimulation and the shape of the ECAP during anaesthesia. We measured the EMG of the first dorsal interosseous muscle during anaesthesia in 36 adults, using Medicotest P-00-S electrodes and a Relaxograph (Revision 01) which prints the

Table 1 Mean (SE) values of the standard pharmacokinetic variables and intercompartmental clearance (Q) for 51W89 and the cis-cis, cis-trans and trans-trans isomers of atracurium Group B atracurium

min
1)

CL(ml V1 (ml) V2 (ml) Q (ml min
1) T½  (min) T½  (min)

Group A 51W89

Cis-cis

Cis-trans

Trans-trans

425 (17.9) 7220 (292) 6450 (433) 234 (27.5) 6.44 (0.46) 34.9 (1.29)

499 (35.1) 71.90 (88) 4400 (752) 277 (105) 4.33 (1.23) 21.9 (1.08)

996 (88) 9930 (1310) 8480 (698) 737 (107) 2.51 (0.194) 18.1 (0.661)

1440 (112) 8410 (1090) 9020 (1270) 731 (92.1) 1.88 (0.226) 15.0 (2.3)

652P ECAP on demand. The ulnar nerve was stimulated at the wrist. The active recording electrode was over the belly of the muscle, the indifferent electrode was on the second finger and the ground electrode was at the distal wrist crease. The arm was laid at the patient’s side, but was not firmly fixed. Anaesthesia was induced with thiopentone 4–5 mg kg1 and the Relaxograph was calibrated; a control ECAP was printed. Atracurium 0.4 mg kg1 was given to 16 patients, whose lungs were intubated and ventilated mechanically to an end-tidal carbon dioxide concentration of 5 kPa. The other 20 patients breathed spontaneously through a laryngeal mask. Anaesthesia was maintained with enflurane 1.5 % and nitrous oxide 66 % in oxygen. The ECAP was printed again when the T1 response was stable, before antagonism of neuromuscular block. The latency, amplitude, negative deflection time (NDT) and area enclosed by the ECAP wave were measured from each ECAP. Results were analysed with Student’s t test and regression analysis, assuming significance at P  0.05. The T1 response decreased to a mean of 85.7 % (95 % confidence interval 81.3–90.1 %) of control in the group who were not paralysed and to 79.7 % (73.3–86.1 %) in the group who had atracurium (P  0.14). The latency, NDT, amplitude and area also did not differ between the groups at any time (P  0.3, t test), so the groups were combined. The decrease in the T1 response correlated significantly with decreases in both amplitude (r  0.83, P  0.001) and area (r  0.56, P  0.001) of the ECAP. There was no correlation between the decrease in the T1 response and the latency (r  0.17) or NDT (r  0.16) of the ECAP. The change in duration of the ECAP during onset of neuromuscular block did not persist into the recovery phase, and was not seen during anaesthesia without neuromuscular block. Key words Monitoring, neuromuscular function. Monitoring, electromyography. Neuromuscular block. References 1. Pugh ND, Harper NJN, Healy TEJ, Petts HV. British Journal of Anaesthesia 1987; 59: 195–199. 2. Harper NJN, Pugh ND, Healy TEJ, Petts HV. British Journal of Anaesthesia 1987; 59: 200–205.

Are changes in the EMG response during anaesthesia caused by failure of supramaximal nerve stimulation? S. L. POLHILL* AND D. C. SMITH Department of Anaesthesia, Southampton General Hospital The control response of the evoked EMG often decreases during anaesthesia, with or without neuromuscular block. The decreased response may be the result of movement of the stimulating electrodes relative to the nerve [1], implying that there is a failure of supramaximal nerve stimulation. We studied 63 patients, ASA grade I or II, having minor surgery. We measured the EMG of the first dorsal interosseous muscle to train-of-four (TOF) stimulation, using Medicotest P-00-S electrodes and a Relaxograph. The ulnar nerve was stimulated at the wrist. A calibrated variable current sink was incorporated into the stimulator circuit, in parallel with the stimulus electrodes. This allowed us to increase the current output from the Relaxograph during calibration while maintaining the supramaximal stimulus current. The active recording electrode was over the belly of the muscle, the indifferent electrode was on the second finger and the ground electrode was at the distal wrist crease. The arm was laid at the patient’s side, but was not firmly fixed. Anaesthesia was induced with propofol 2–2.5 mg kg1 and the Relaxograph was calibrated at the loss of the eyelash reflex. The patients breathed spontaneously, through a laryngeal mask, a mixture of isoflurane 1–1.5 % and nitrous oxide 66 % in oxygen. The Relaxograph measured the response to TOF stimulation every 20 s. When the first (T1) response to TOF was stable, after at least 20 min of anaesthesia, the amount of current passing through the sink was reduced, effectively increasing the stimulus current to the ulnar nerve. In 45 patients the Relaxograph calibration routine was then repeated. Results are presented as mean (95 % confidence interval). There was no change in the EMG response in 13 patients. In the remaining 50 patients the response decreased to 78.4 %

British Journal of Anaesthesia (70.9–85.9 %) of control over the first 20 min of anaesthesia. In 22 of 50 patients, increasing the stimulus current by a mean of 12.3 mA increased the T1 response from 71.4 % (62.0–80.8 %) to 92.2 % (88.2–96.2 %). In 18 of these 22 patients, the mean supramaximal stimulus current at recalibration increased from 52.5 to 64.8 mA. In 28 of 50 patients the T1 response did not change when the stimulus current was increased; in these patients the mean supramaximal current at recalibration was the same as at the original calibration (49.1 vs 49.7 mA). Loss of supramaximal stimulation was at least partly responsible for the decrease in the EMG response during anaesthesia. We could not explain why increasing the stimulus current increased the measured response in only half of the patients who had a decrease in the control response. Key words Monitoring, neuromuscular function. Monitoring electromyography. Reference 1. Smith DC, Booth JV. British Journal of Anaesthesia 1994; 72: 407–410.

Observations on phrenic nerve function during coronary artery surgery Z. P. KHAN*, J. PONTE, G. H. MILLS*, M. I. POLKEY*, J. DESAI* AND J. MOXHAM* Departments of Anaesthetics, Thoracic Medicine and CardioThoracic Surgery, King’s College Hospital, London Phrenic nerve injury and diaphragmatic dysfunction are well recognized complications of cardiac surgery [1]. It has been reported that the use of topical ice slush and diathermy for dissection of the internal mammary artery [IMA] increases the incidence of such complications. We used a non-invasive, newly developed method of unilateral phrenic nerve stimulation to study the effects of bilateral IMA harvesting and the application of topical ice slush to the heart on the evoked electromyographical responses (EMG) of the diaphragm during cardiac surgery. Unilateral, magnetic, transcutaneous, single twitch stimulation of the phrenic nerve was performed on 12 patients, with a 43-mm double coil, powered by a “Magstim 200”, using an anterolateral approach on the neck, before and after dissection of each IMA. The EMG was recorded from needle electrodes placed directly in both domes of the diaphragm. All patients received 2 mg kg1 of suxamethonium at induction of anaesthesia to facilitate intubation of the trachea and no further neuromuscular blocking drugs were given. Any diaphragmatic twitching caused by diathermy was noted. In four of the patients the left phrenic nerve Was stimulated before and at 5-min intervals for 55 min after the application of topical ice slush to the heart. IMA dissection had no effect on the latency, amplitude or duration of the evoked compound action potential of the diaphragm, although diathermy-induced twitches were seen in all patients. The effect of topical ice slush on the evoked EMG response of the left diaphragm is illustrated in figure 1.

Figure 1 Effect of ice placed around the heart on the evoked EMG response of the diaphragm to single magnetic pulses applied to the left phrenic nerve. Arrows indicate the stimulus artefact; (A) just before ice application, (B) 5 min after ice application, and (C) 55 min later.

Proceedings of the Anaesthetic Research Society The lack of observable effects of dissection of the IMA on the diaphragmatic EMG response may have been because of the small number of patients studied or, possibly, an unconscious change in the strategy of dissection of the IMA resulting from the visible twitching of the diaphragm in response to diathermy. To our knowledge this was the first demonstration of the effect of local cooling on phrenic nerve conduction in human subjects, using magnetic stimulation. Key words Surgery, cardiovascular. Arteries, internal mammary artery. Nerve, phrenic nerve. References 1. Devita MA, Robinson LR, Rehclev J, Hattler B, Cohen C. Chest 1993; 103: 850–856.

Performance assessment of a fuzzy controller for atracurium-induced neuromuscular block D. G. MASON*, N. D. EDWARDS, D. A. LINKENS AND C. S.

REILLY Department of Automatic Control & Systems Engineering and Department of Anaesthetics, University of Sheffield Closed-loop computer control offers the ability to provide a stable level of muscle relaxation allowing for variations in individual patient responses to neuromuscular blocking agents. Fuzzy logic control is a simple although powerful technique for automation in anaesthesia [1]. Computer simulation studies showed good feasibility of a fuzzy controller for closed-loop control of neuromuscular block with atracurium [2]. We have now assessed the performance of our control system under clinical conditions. After Ethics Committee approval 10 ASA I or II patients gave informed consent for inclusion in this evaluation. Anaesthesia was induced with alfentanil 10
g kg1 and a sleep dose of propofol. Each patient was ventilated manually while a Datex relaxograph was calibrated. A general purpose computer instructed a Graseby Medical GM3400 infusion pump to administer a loading dose of atracurium 0.33 mg kg1 which facilitated tracheal intubation. Anaesthesia was maintained with a propofol infusion, nitrous oxide and oxygen, and morphine as appropriate. The time taken for T1 to recover to 5 % after the loading dose was used to measure each patient’s sensitivity to atracurium and thus determine the initial infusion rate. Initially T1 was controlled with setpoint  10 % for approximately 30 min (control phase I). The T1 setpoint was then increased to 20 % and then returned to 10 % for two further 30-min periods (control phases II and III). T1 errors (actual T1 value minus setpoint T1 value) for each control phase were analysed separately using data logged by the computer. Means and standard deviations (SD) for the 10 patients were calculated for each of the mean error, point count (PC  proportion of T1 data points with positive error), and standard control engineering measures of transient performance (integral square error (ISE)) and steady state performance (integral time absolute error (ITAE)). Results are summarized in table 2. These showed accurate control with good transient responses and robustness to setpoint changes despite the significant non-linear and uncertain individual responses to neuromuscular block. Key words Computers, fuzzy logic control. Neuromuscular block, atracurium.

653P References 1. Martin JF. Journal of Clinical Monitoring 1994; 10: 77–80. 2. Mason DG, Linkens DA, Edwards ND, Reilly CS. IEEE Engineering in Medicine and Biology 1994; 13: 678–686.

Effect of stabilization on the onset of neuromuscular block when assessed using accelerometry K. J. GIRLING AND R. P. MAHAJAN University Department of Anaesthesia, Queen’s Medical Centre, Nottingham McCoy and co-workers have shown recently that a progressive and significant reduction in onset to maximal neuromuscular block occurs as the time of stabilization of muscle twitch before injection of neuromuscular blocking drug increases from 1 to 20 min [1]. Recently, Rédai and colleagues suggested that this phenomenon may be the result of some monitoring systems being influenced by the period of stabilization [2]. Accelerometry is increasingly being used for monitoring neuromuscular block in research and clinical practice. We sought to determine if this system is sensitive to the period of stabilization. We recruited 20 ASA I–II patients undergoing elective surgery for which they would require general anaesthesia and neuromuscular block. No premedication was given and anaesthesia was induced with alfentanil 10
g kg1 and propofol 3 mg kg1. The patients were allowed to breathe an oxygen/air mixture spontaneously via a laryngeal mask with anaesthesia maintained using a propofol infusion at 10 mg kg1 h1. Once settled, both hands were positioned for ulnar nerve stimulation and an accelerometer (Tof-guard, Biometer International, Odense, Denmark) was attached to each wrist. Having confirmed that both accelerometers were functioning correctly and having identified the supramaximal stimulus, one of the ulnar nerves was stimulated using a train-offour pattern at 15-s intervals. After 17 min, stimulation of the contralateral ulnar nerve was commenced and then after a further 3 min the neuromuscular blocking drug was given. The first 10 patients received vecuronium 0.1 mg kg1 and the subsequent 10 received atracurium 0.5 mg kg1. The time taken to onset of maximal block was recorded by the Tof-guard. The data collected were subjected to a paired t test with P  0.05 taken as significant. No significant difference was found in the onset time of vecuronium or atracurium after 3 or 20 min of stabilization (table 3). We concluded that there was no difference in the onset of neuromuscular block with either vecuronium or atracurium when assessed by accelerometry using a train-of-four stimulus every 15 s after stabilization for 3 or 20 minutes. Key words Neuromuscular block, measurement of response. Measurement techniques: neuromuscular block. Acknowledgement We thank Organon Teknika for supporting this study. References 1. McCoy ÉP, Mirakhur RK, Connolly FM, Loan PB. Anesthesia and Analgesia 1995; 80: 364–7. 2. Rédai I, England AJ, Feldman SA. British Journal of Anaesthesia 1995; 4: 474P.

Effect of reduced density gas breathing on oxygenation in spontaneously breathing anaesthetized patients

Table 2

A. DEVINE, P. C. W. BEATTY, A. J. MORTIMER AND I. T. CAMPBELL University Department of Anaesthesia, Withington Hospital, Manchester

Summary of T1 error analysis (mean (SD))

Control Phase

T1 error (%)

PC (%)

ISE (%)

ITAE

I II III

1.4 (1.1)
0.37 (1.2) 0.89 (0.93)

77 (16) 40 (29) 60 (17)

3.8 (2.0) 1.4 (0.5) 5.0 (2.5)

27 (24) 7.3 (2.6) 26 (25)

Alveolar-arterial (A-a) oxygen tension gradient increases during general anaesthesia, when ventilation is both spontaneous and mechanically assisted owing to altered ventilation-perfusion distribution [1]. In awake volunteers, A-a oxygen gradient rises by 0.9 kPa with heliox compared with air [2]. We wished to see what

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British Journal of Anaesthesia Table 3

Comparison of time to maximal block(s) in the two arms (3 and 20 min) for vecuronium and atracurium Vecuronium onset(s) Patient

20 min

1 120 2 165 3 105 4 120 5 120 6 120 7 135 8 135 9 165 10 195 Mean difference (SEM) P

Table 4

He/O2 N2/O2 P

Atracurium onset(s)

3 min

Diff.3–20

20 min

3 min

Diff.3–20

210 150 105 105 120 135 135 135 180 210

90
15 0
15 0 15 0 0 15 15 10.5 (9.5) 0.15

135 135 105 105 105 135 120 90 150 90

120 135 120 105 120 150 105 105 150 75


15 0 15 0 15 15
15 15 0
15 1.5 (4.15) 0.36

Mean (SD) partial pressures in the two groups (kPa)

Nitrous oxide in a very low-flow breathing system

( PAO2 − PaO2 ) (PACO 2

J. D. WATTS, M. R. NEL* AND G. G. LOCKWOOD Department of Anaesthesia, Hammersmith Hospital, London

14.5 (6.45) 18.5 (4.31) 0.02

− PaCO2 ) PaO2

1.6 (0.48) 1.2 (0.37) 0.03

PaCO2

16.3 (3.86) 6.9 (1.02) 15.1 (3.54) 6.8 (1.02) NS NS

effect reducing the breathing gas density using helium would have on A-a gradient during anaesthesia. Ten ASA I-III patients with normal spirometry undergoing elective surgery were anaesthetized with propofol and alfentanyl infusions. Patients breathed spontaneously using a laryngeal mask and a Blease circle system with a carbon dioxide absorber. A mixing box was placed in the expiratory limb of the breathing system to measure mixed expired gas. Each patient was chosen randomly to breath either helium and 40 % oxygen or 40 % oxygen in nitrogen as the first gas. The fresh gas flow was set at 4 litre min1 for 20 min. Gas flow was then reduced to 300 ml min1 (Capnomac sampling rate 200 ml min1), the expiratory valve of the breathing system was closed, and after a further 5 min inspired, end-tidal and mixed expired carbon dioxide and oxygen were measured. Arterial blood gases were measured. The second gas mixture was then introduced and the procedure repeated. The A-a oxygen gradient was calculated from the alveolar gas equation of Filley, MackIntosh and Wright [3]. Table 4 shows that there was no difference in arterial oxygen or carbon dioxide when breathing helium-oxygen compared with oxygen enriched air. A-a oxygen gradient was significantly lower and carbon dioxide gradient was significantly higher with helium-oxygen compared with oxygen in air. The lower A-a oxygen gradient with helium when breathing spontaneously during anaesthesia contrasts with the findings in awake volunteers. This may be the result of improved ventilation distribution or increased importance of diffusion compared with convection during anaesthesia with the lower density gas. Key words Gases non-anaesthetic, helium. Lung, alveolar-arterial oxygen tension gradient. Acknowledgement We wish to thank BOC Limited for their support. References 1. Bindeslev L, Hedenstierna G, Santesson J, Gottlieb I, Carvallhas A. Acta Anaesthesiologica Scandinavica 1981; 25: 360–371. 2. Liese W, Muysers-K, Pichotka JP. Pflϋgers Archives 1970; 321: 316–331. 3. Filley GF, MacIntosh DJ, Wright GW. Journal of Clinical Investigation 1954; 33: 530–535.

A trunk of corrugated tubing may be used instead of a bag-inbottle to separate the gas in a closed breathing system from that in an open system. The gas within the trunk can be used to supply, basal oxygen to the closed system instead of a conventional fresh gas supply [1]. Anaesthesia can then be maintained by VIC, direct injection of anaesthetic into the breathing system or i.v. techniques. Delivery of nitrous oxide into this type of closed system is particularly problematic. If the trunk contains a 50 % mixture of nitrous oxide in oxygen then hypoxia will develop in a closed system as both nitrogen and nitrous oxide accumulate. One solution to the problem is to allow a controlled leak which will slowly but continuously flush the breathing system, and a convenient implementation would be to use the gas analyser’s sample flow, and measured to be 180 ml min1. We have investigated this possibility. An estimate of the eventual oxygen concentration in breathing system gas may be calculated by considering the rate it is supplied to and lost from the system. oxygen supply=FtrankO2 ⋅ (V!O2 + V!N2O + V!leak − V!N2 ) oxygen loss=V!O2 + (V!leak ⋅ FsystemO2) where FtrankO2 and FsystemO2 represent the fractional concentration of oxygen in the trunk and breathing system reipeetiyely and Vleak is the sample rate. Equating these and using values for oxygen and nitrous oxide uptake from Svensson and colleagues [2], and, values for nitrogen elimination from Barton and Nunn [3], the final oxygen fraction is predicted to be 0.28 when the trunk oxygen fraction is 0.5. We studied 16 patients undergoing orthopaedic surgery for an average of 83 (range 40–160) min each with anaesthesia maintained by direct injection of liquid desflurane into the breathing system (FE des 0.08). F I O2 became less than 0.3 in seven cases, at least 60 min after introducing nitrous oxide into the trunk. Surprisingly, these included all five male subjects. The technique therefore does not always maintain the inspired oxygen concentration above a commonly accepted minimum level. However, extrapolation of our data and the theoretical considerations-above suggest that, in contrast with the use of 50 % nitrous oxide in the fresh gas supply to a completely closed system, absolute hypoxia will not occur. In that respect the modest opening of. the breathing system caused by the leak may be judged a useful safety feature. Key words Anaesthesia, breathing systems. Anaesthetics gases, nitrous oxide. References 1. Jordan MJ, Bushman JA. British Journal of Anaesthesia 1981; 53: 1285–1290. 2. Svensson KL, Henrikson B-Å, Sonander H, Stenqvist O. British Journal of Anaesthesia 1990; 64: 320–326. 3. Barton F, Nunn JF. British Journal of Anaesthesia 1975; 47: 350–357.

Proceedings of the Anaesthetic Research Society Effect of respiratory obstruction on peak carbon dioxide concentrations in sleeping children using nasal capnography T. C. SMITH AND P. HUTTON University Department of Anaesthesia and Intensive Care, Queen Elizabeth Hospital, Birmingham We aimed to identify differences in peak carbon dioxide concentrations between obstructing and non-obstructing children, and the effect of adenotonsillectomy. Sixty children having adenotonsillectomy were assigned to one of two groups on the basis of clinical history alone. The “obstructers” were 30 patients with a history of sleep-induced respiratory obstruction. The “non-obstructers” were 30 patients with recurrent tonsillitis and no obstructive history. The “controls” comprised 11 volunteers not undergoing adenotonsillectomy and without a history of obstruction. The groups were comparable in other respects. All the children were studied on the first night of admission to hospital. The “obstructers” were also studied on the first postoperative night and 1 month later. Nasal carbon dioxide concentrations were sampled continuously overnight using an Engström Eliza capnograph. The analogue signal was stored on VHS video tape in a digital format using a PCM-4 converter (Digitimer). The reproduced capnograms were analysed by the capnogram analysis program CAPNOG [1]. CAPNOG calculates 10 variables for each capnogram breath and stores them as ASCII text. For each patient, a peak end-tidal carbon dioxide concentration was calculated as the average of the highest 30 values over the first 3 h of sleep. This is representative of a full overnight recording. Figure 2 shows that peak concentrations of carbon dioxide were considerably higher in the obstructors on the preoperative night than in any of the other groups. These differences were significant both clinically and statistically (t test, P  0.001). There was no difference between the non-obstructers and the controls. “Obstructers” had higher peak concentrations of end-tidal carbon dioxide than “non-obstructers”. Adenotonsillectomy removes these differences almost immediately. The concentrations of end-tidal carbon dioxide in all these sleeping children are above the generally, considered upper limit of normal. This minimally invasive method may identify children with significant sleepinduced respiratory obstruction.

Key words Gases non-anaesthetic, carbon dioxide. Ventilation, partial pressure. Sleep apnoea.

Reference 1. Patil C, Stokes MA, Clutton-Brock TH, Hutton P. British Journal of Anaesthesia 1989; 63: 634–635P.

655P Comparison of morphine and pethidine given by PCA for postoperative pain J. Plummer*, H. OWEN, S. INGLIS* AND A. ILSLEY* Department of Anaesthesia and Intensive Care, Flinders Medical Centre, Adelaide, South Australia There is much anecdotal evidence concerning the relative merits of morphine and pethidine in the treatment of postoperative pain, but few well designed trials have addressed this issue. This double blind, randomized trial compared morphine and pethidine in terms of efficacy and side effects. Eighty-two patients, aged between 21 and 90 yr, scheduled for upper abdominal surgery were assigned randomly to receive pethidine, bolus dose size 9, 12 or 18 mg, or morphine, bolus dose size 0.75, 1.0 or 1.5 mg, by patient-controlled analgesia (PCA) for postoperative pain. The lockout interval was 5 min. Patients completed trail-making tests A and B (measures of neuropsychological function), and the Multiple Affect Adjective Check List (MAACL) (a measure of mood), preoperatively and after 24 and 48 h of PCA use. Dryness of the mouth (absent or present), pain on sitting (0  none to 5  unable to sit because of pain), and severity of nausea (0  none, 1  mild, 2  severe, 3  withdrawn because of uncontrolled nausea) were also assessed at 24 and 48 h. At 48 h patients were asked if they had had any unusual dreams. Statistical analysis was by chi-square test or by repeated measures analysis of variance using age or preoperative scores as covariates where appropriate; P  0.05 was considered significant. Nausea scores and MAACL scores for anxiety, depression and hostility did not differ significantly between morphine and pethidine groups. Incidence of dryness of the mouth was significantly greater with pethidine than with morphine at both 24 h (95 % vs 79 %) and 48 h (86 % vs 59 %). Pain on sitting was significantly greater in patients receiving pethidine (table 5). 16 % of patients receiving morphine and 24 % of those receiving pethidine reported unusual dreams (P  0.4). Time to complete trail-making test A (P  0.01) but not the more complex test B (P  0.98) was longer in the pethidine than in the morphine group. The difference between morphine and pethidine groups in time to complete trail-making test A was greatest with the largest bolus dose size; no other outcomes were significantly associated with bolus dose size. Table 5 Pain on sitting (morphine vs pethidine P  0.015, 24 h vs 48 h P  0.017, age (covariate) P  0.020) Morphine 24 h mean 2.1 1.1 SD 48 h mean 1.7 0.9 SD

Pethidine 2.4 1.0 2.3 0.8

Pethidine was less effective than morphine in controlling pain on movement and was associated with a higher incidence of dryness of the mouth. Differences between the drugs were, however, modest and pethidine should be considered a viable option where morphine is unsuitable. Key words Analgesics opioid, morphine. Analgesics opioid, pethidine. Acknowledgement The authors are grateful to Graseby Medical Limited, Watford, UK, for the loan of model 3300 PCA pumps used in this study.

Citation of anaesthesia abstracts in original papers published in five anaesthesia journals N. W. GOODMAN AND N. STRATFORD University Department of Anaesthesia, Southmead Hospital, Bristol Figure 2 Peak end-tidal carbon dioxide concentrations by group (mean and 95 % confidence intervals). ((A) before operation; (B) after operation; (C) 1 month later.)

Previous work is cited for at least three reasons: “to credit the original workers ...; to relate to the ... methods and findings;

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British Journal of Anaesthesia

and ... to enable [consultation of] the referenced materials” [1]. In summary, citation is for precedence, context and support. A common way to establish precedence is to present and publish an abstract before the definitive paper. Dual publication is frowned on [2], but abstracts of work in progress or of completed work are an accepted form of scientific communication. Full publication should follow, and subsequent citation should be to that. Some journals do not allow citation of abstracts after a defined interval, on the grounds that this is evidence that the work was in some way flawed. This may not be true, but it does suggest that the work has not made the necessary step for full acceptance by the scientific community, by either failing peer review, or not being presented for it. Abstracts establish precedence, but only if the abstracts are actually cited. Hamilton [3] reported that only about half of all published full papers are cited, and that up to 20 % of all citations are self-citations. We assessed the citation of abstracts in the first 3 months’ issues of 1995 in five journals: the British Journal of Anaesthesia (BJA), Anaesthesia (Anaes), Anesthesiology (Anesth), Anesthesia and Analgesia (A and A) and the Canadian Journal of Anaesthesia (CJA). Table 6 Number of original papers, and of papers citing at least one abstract, in five anaesthesia journals from first 3 months of 1995 (abbreviations as in text); number of published abstracts in that journal for whole of 1994. (ARS, Anaesthetic Research Society; ESA, European Society of Anaesthesiologists; ASA, American Society of Anesthesiologists; IARS, International Anesthetic Research Society; CSA, Canadian Society of Anaesthetists.)

Journal BJA Anaes Anesth A and A CJA Total

Papers

Papers citing any abstracts

Papers self-citing abstracts

54

26

9

35 76 78 29 272

9 29 24 10 98

1 17 8 2 37

Society and abstracts ARS ESA — ASA IARS CSA

91 244 — 1492 503 115 2445

Investigators cited abstracts in about one-third of papers, and about two-thirds of these papers had citations to abstracts that were not the investigators’ own. If the numbers in table 6 are representative of a whole year, and from year to year, then about 400 papers will have citations to abstracts in 1995, which means that about one in six published anaesthesia abstracts is cited in these five journals. We have not compared formally rates of citation of abstracts of each society, or of each society in each journal, but the crude annual rate of citation of ARS abstracts was 40 of 91, and of ASA abstracts was 272 of 1492. Most of the papers in which ARS abstracts were cited were published in the British journals. We conclude that it is worthwhile to publish abstracts. Key words Anaesthesia. Publications citation. Publications, abstracts. References 1. Biebuyck JF. Anesthesiology 1992; 77: 1–2. 2. Lock S. British Medical Journal 1984; 288: 661–662. 3. Hamilton DP. Science 1990; 250: 1331–1332.

Volatile anaesthetics and barbiturates have different actions on the input resistance of an Identified molluscan neurone M. QAZZAZ* AND W. WINLOW Department of Physiology, University of Leeds, Leeds Identified neurones of the pond snail Lymnaea stagnalis are models for investigating the cellular mechanisms underlying general anaesthesia. Anaesthetics may either decrease discharge

Figure 3 Effect of volatile anaesthetics and barbiturates on input resistance of VD1 in Lymnaea stagnalis,( ; Control; phase 1; phase 2; 1 %; 2 %). frequency and cause eventual quiescence in some Lymnaia neurones [1], or cause paroxysmal depolarizing shifts (PDS) before quiescence in others [2]. Here we demonstrate the actions of volatile anaesthetics and pentobarbitone on the input resistance of the neurone VD1. The brain of Lymnaea was prepared as described previously [3], VD1 was desheathed and recordings were made using standard electrophysiological techniques. A 0.1-nA hyperpolarization current was injected for 1 s before, during and after perfusion of the anaesthetics. The preparation was perfused with pentobarbitone 0.5 mmol litre1 and 2 mmol litre1 1 % and 2 % isoflurane or halothane. Alterations in the amplitude of the hyperpolarizing current pulses gave indication of changes in the input resistance (which is inversely proportional to membrane conductance) at each stage of the experiment. We found that both volatile anaesthetics decreased the input resistance in a dose-dependent manner. Further, the decrease in the input resistance induced by halothane was significantly greater than that induced by isoflurane (P  0.01.) it both concentrations (fig. 3). Pentobarbitone induced two differert phase of activity. In the first phase, when the cell exhibits PDS, the input resistance increased significantly but with no dose dependency (P  0.01), and in the second phase, when the cell becomes quiescent, there was no significant change in input resistance (fig. 3). Thus barbiturates and volatile anaesthetics had different actions on the input resistance of VD1. The input resistance of VD1 was significantly increased during the first phase PDS induced by both concentrations 0.5 and 2 mmol litre1 of pentobarbitone (n  6, P  0.01; Student’s unpaired t test) but there was no significant change in the second phase when the cell goes quiescent. The input resistance was significantly decreased by 1 % and 2 % isoflurane (n  4, P  0.01) in a dose-dependent manner. Halothane 1 % and 2 % induced a greater reduction in input resistance in comparison with isoflurane (P  0.0.1). Key words Anaesthetics volatile. Nerve, neurotransmitters. Model, mollusc. Acknowledgements Supported by a grant from Ohmeda. MQ was supported by Arab Student Aid International and The Palestine Studies Trust. References 1. Winlow W, Yar T, Spencer G, Girdlestone D, Hancox J. General Pharmacology 1992; 23: 985–992. 2. Fathi-Moghadam H, Winlow W. IUPS 1993; 205: 42P.

Proceedings of the Anaesthetic Research Society 3. Benjamin PR, Winlow W. Comparative Biochemistry and Physiology 1981; 70: 293–307.

657P Dexmedetomidine decreases dose and concentration of propofol required to suppress consciousness A. H. CLOOTE*, C. J. PEDEN*, N. STRATFORD*,

Haemodynamic changes associated with dexmedetomidine, propofol and alfentanil anaesthesia C. J. PEDEN*, A. H. CLOOTE*, N. STRATFORD*, S. M. ROBINSON* AND C. PRYS-ROBERTS Sir Humphry Davy Department of Anaesthesia, Bristol Royal Infirmary The alpha2-agonists, clonidine and dexmedetomidine, have been used as adjuncts to general anaesthesia. One of the main advantages of these drugs may be that they produce marked perioperative haemodynamic stability [1, 2]. As part of a doseresponse study using total i.v. anaesthesia with dexmedetomidine, propofol and alfentanil, we collected perioperative haemodynamic information to examine this hypothesis. All ASA class I and II patients studied were aged between 18 and 40 yr, weighed 100 kg and had a preoperative ECG. They received one of three concentrations of a two-step infusion of dexmedetomidine (level I, 70 ng kg1 min1 for 15 min followed by 7 ng kg1 min1; level II, 40 ng kg1 min1 then 4 ng kg1 min1; level III, 30 ng kg1 min1 then 3 ng kg1 min1). After a 15-min loading dose of dexmedetomidine, the patients received one of five different doses of a stepped propofol infusion. When the final propofol infusion concentration was reached the patients were given alfentanil 50
g kg1 and an infusion of alfentanil 50
g kg1 h1. Suxamethonium 1 mg kg1 was used for intubation. IPPV was commenced using 30 % oxygen in air. PETCO2 was maintained at 30 (SD) mm Hg. The patients were monitored with ECG, NIBP and pulse oximetry. Blood pressure was recorded at 3-min intervals for 30 min after the start of dexmedetomidine, then at 5-min intervals, and at 15-min intervals for 2 h in recovery. Forty-nine patients were studied: three patients received level I dexmedetomidine; six patients level II; and 40 level III. Adverse reactions, particularly bradycardias, occurred with the first two dose levels; because of this the dose of dexmedetomidine for further patients was decreased. The 40 level III patients all received glycopyrronium 5
g kg1 before starting dexmedetomidine. In this large group no significant bradycardias occurred. The mean pulse rate decreased after induction in groups I and II by 24 bpm and 4 bpm respectively. The mean pulse rate in group I then remained the same during surgery and in the recovery ward, in group II it decreased further by 8 bpm during surgery and 2 bpm in recovery. In group III, pulse rate increased from a mean baseline of 73 bpm to 75 bpm, possibly due to the glycopyrronium, and then decreased to 62 bpm during surgery and in recovery. Blood pressure measurements were quite stable in all three groups, with no significant differences between the groups. In the 40 patient group the mean baseline blood pressure was 135 (SD 14) mm Hg; this decreased to 116 (14) mm Hg after induction and before surgery, and to 106 (14) mm Hg during surgery. In recovery the mean blood pressure was 116 (12) mm Hg. We recommend that anticholinergic agents should be used in combination with alpha2-agonists especially when other drugs known to cause bradycardias such as propofol and alfentanil are used. Key words Anaesthetics i.v., propofol. Analgesics opioid, alfentanil. Blood, haemodynamics. References 1. Maze M, Tranquilli W. Anesthesiology 1991; 74: 581–605. 2. Longnecker DE. Anesthesiology 1987; 67: 1–2.

M. A. TOOLEY* AND C. PRYS-ROBERTS

Sir Humphry Davy Department of Anaesthesia, Bristol Royal Infirmary Dexmedetomidine is a selective alpha2-adrenoceptor agonist. It is almost 10 times more selective than clonidine for the alpha2adrenoceptor. Previous studies have shown a decrease in the requirements for both thiopentone and isoflurane during anaesthesia when dexmedetomidine was used as an adjunct [1, 2]. We have determined the effect of dexmedetomidine in decreasing the propofol requirement to suppress consciousness under quasi steady state infusion conditions in young patients. Forty healthy patients (20–40 yr) undergoing superficial body surgery received i.v. dexmedetomidine in a two-step infusion scheme designed to achieve a stable concentration of 0.6 ng ml1. Patients were then allocated randomly to receive propofol by one of five different manually-controlled infusion schemes designed to achieve and maintain a stable blood concentration between 1 and 3
g ml1, covering a range of states between conscious sedation and full anaesthesia. After 20 min the patients were asked to respond to verbal command, and venous blood samples were withdrawn for analysis of whole blood propofol concentration by high performance liquid chromatography. Dose- and concentration-response curves were constructed by probit analysis (SAS for PC, version 6.04) and the results were compared with those for propofol alone in a group of patients of similar age and sex distributions [3]. No patients failed to respond to command during dexmedetomidine infusion or before the start of propofol infusion. During dexmedetomidine infusion the ED50 for the final infusion rate of propofol to abolish consciousness (loss of response to verbal command) was 3.45 (95 % confidence limits (CL) 2.68–4.21) mg kg1 h1; ED95 was 6.68 (95 % CL 5.07–19.05) mg kg1 h1. These values are significantly lower (P  0.01) than those derived using propofol alone of ED50 5.79 (3.47–6.8) mg kg1 h1 and ED95 8.31 (7.05–16.9) mg kg1 h1. The EC50 for propofol for suppression of consciousness was 1.69 (95 % CL 0.95–2.5)
g ml1 in patients who received dexmedetomidine, and 2.3 (95 % CL 1.8–2.7)
g ml1 in those who received propofol alone (P  0.05). Although testing for differences in proportions (Fisher’s exact test) of patients responding at a given dose or concentration of propofol showed significant differences at the 5 % level, analysis of variance (with correction for the probit transformation) showed no significant differences between the dose- or concentration-response curves. Key words Sympathetic nervous system, alpha2-adrenoceptor agonists. Anaesthetics i.v., propofol. Acknowledgement The authors thank Orion Farmos for financial support. References 1. Aantaa R, Kanto J, Scheinin M, Kallio A, Scheinin H. Anesthesiology 1990; 73: 230–235. 2. Aho M, Lehtinen A-M, Erkola O, Kallio A, Korttila K. Anesthesiology 1991; 74: 997–1002. 3. Forrest F, Tooley M, Saunders P, Prys-Roberts C. British Journal Anaesthesia 1994; 72: 35–41.

Intraocular pressure decreases during intubation under propofol J. P. RICHARDS* AND J. S. HAMMOND* Department of Anaesthetics, Royal Preston Hospital, Preston A previous study [1] has shown that propofol and alfentanil, without neuromuscular block can provide comparable intubating conditions and a stable haemodynamic response when compared with thiopentone and suxamethonium, which are known to increase intraocular pressure [2]. We have investigated the changes that occur in intraocular pressure during induction of anaesthesia and intubation.

658P Table 7 test)

British Journal of Anaesthesia Mean values (range) *P  0.014 **P  0.001 (paired t

IOP (mm Hg) SysAP Heart rate (bpm)

Thio/Sux (n  21) Pre-ind

3 min

Prop/Alf (n  19) Pre-ind

11.1** (1–20) 144** (114–182) 79** (52–130)

20.4 (8–34) 177 (116–222) 104 (70–156)

12.8** 4.7 (3–19) (0–10) 130** 110 (104–171) (74–172) 80* 73 (48–116) (48–103)

Table 8 Median (range) platelet count and aggregation in platelet rich plasma (* P  0.05) Platelet count (
109 litre1)

Platelet aggregation (%)

296 (262–397)

72 (5l–87)

174 (144–260)* 190 (131–269)* 175 (126–241)*

70 (22–79) 55(30–73) 47 (21–79)*

175 (144–216)* 167 (110–274)* 181 (120–263)*

63 (19–75) 52 (19–81)* 43 (13–63)*

3 min

Informed written consent was obtained from 46 ASA I patients presenting for elective surgical procedures lasting more than 20 min and requiring tracheal intubation. Obstetric, neurology and ophthalmology patients were excluded. All patients were unpremedicated, preoxygenated for 3 min, venous access secured and monitoring applied in the anaesthetic room. Patients were allocated randomly into two groups. Group TS received thiopentone 5 mg kg1 over 30 s followed by suxamethonium 1 mg kg1. Laryngoscopy was performed 60 s later, and fentanyl 100
g given after intubation. Group PA received alfentanil 50
g kg1 followed by propofol 2.5 mg kg1 over 30 s, and 60 s later laryngoscopy was performed. In both groups anaesthesia was maintained subsequently with isoflurane 1 % in nitrous oxide and oxygen. Intraocular pressure (measured with a Perkins explanation tonometer) and routine physiological data were recorded immediately before and at 1 min intervals for the first 7 min after induction. Two patients from the TS and four from the PA group were excluded from further analysis because of incomplete data collection, excessive movement or inadequate relaxation. We have analysed data from 40 patients. Intraocular pressure was noted to increase from 11.1 mm Hg to 20.4 mm Hg in the TS group, and decrease in the PA group from a mean value of 12.8 mm Hg to 4 mm Hg at 3 min after the start of induction. Both blood pressure and heart rate followed the general trends of the intraocular pressure changes (Table 7). Two patients in the TS group coughed at intubation compared with eight in the PA group, while movement occurred in six of the TS group and one of the PA group. We found the intubating conditions at 90 s from induction are comparable with those found in our previous study [1]. Furthermore, we demonstrated a significant decrease in intraocular pressure when using propofol and alfentanil, which may have advantages for patients with penetrating or open eye injuries.

Control Propofol (
g ml1) 2.5 10 20 Intralipid (
g ml1) 25 100 200

2
mol litre1 adenosine diphosphate and measured using a turbidometric technique. Platelet-poor plaima was used for calibration of maximum light transmission. A sample of control plasma was exposed to 2 % halothane in oxygen for 10 min before and during aggregometry. Platelet counts and aggregation were compared with control using Friedmann’s analysis for repeated measures. In the control sample whole blood platelet count was 209 (179–288)
109 litre1 and in all other groups it was significantly lower (P  0.05). As shown in table 8, platelet counts in plateletrich plasma were substantially lower than control in all groups. Platelet aggregation was significantly reduced by the higher concentrations of propofol and Intralipid. Halothane reduced aggregation to 61 (8–73)%. Propofol and Intralipid caused a reduction in both platelet count and aggregation. We postulate that Intralipid caused activation of the most reactive platelets and to reduced platelet count and left a less reactive subpopulttion. Remaining ptatelets showed a reduction in aggregation, similar to that with 2 % halothane. Key words Anaesthetics i.v., propofol. Blood, platelet aggregation. References 1. Dalsgaard-Nielson J, Gormsden J. Thrombosis and Haemostasis 1980; 44: 143–145. 2. Wallis CB, Williams DR, McLean M, Belch JJF, Macrae WA. British Journal of Anaesthesia 1995; 75: (suppl. 1) 82.

Key words Eye, intraocular pressure. Anaesthetics i.v., propofol.

Calcium sensitivity of skinned muscle fibres correlates with the rapidity and severity of symptom development in the clinical reactions of malignant hyperthermia susceptible probands

References 1. Beck GN, Masterson GR, Richards J, Bunting P. Anaesthesia 1993; 48: 876–880. 2. Cook JH. Anaesthesia 1981; 36: 359–365.

P. D. SMITH, P. M. HOPKINS, F. R. ELLIS, P. J. HALSALL AND L. R. BRIDGES Academic Unit of Anaesthesia, University of Leeds, St James’s University Hospital, Leeds

In vitro study of the effect of propofol, intralipid and halothane on platelet aggregation A. J. MCDIARMID AND C. B. WALLIS Department of Anaesthetics, Ninewells Hospital, Dundee Halothane has been shown to inhibit platelet aggregation reversibly in a dose-dependent manner [1], and our previous work has shown an apparent reduction in platelet aggregation during total i.v. anaesthesia with propofol [2], However, it was unclear whether propofol or its vehicle, 10 % Intralipid was responsible. The present study aimed to compare the effects of propofol, Intralipid and halothane on platelet aggregation in vitro. Blood from 10 healthy volunteers was citrated. Propofol was added giving concentrations of 2.5, 10 and 20
g ml1 and identical volumes of 10 % Intralipid added giving concentrations of 25,100 and 200
g ml1 and incubated at 37 C for 10 min. A control sample had no additive. A platelet count was performed on all samples. Platelet-rich plasma was then prepared by centrifugation and platelet counts repeated. Platelet aggregation was activated by

Clinically malignant hyperthermia presents with multiple signs relating to skeletal muscle hypermetabolism of variable intensity and time course. We have demonstrated a substantial betweenpatient variability in tension and rate of tension development in skinned muscle fibres at low calcium concentrations [1]. Skinned muscle strips had their sarcoplasmic reticulum destroyed by Brij 58. Myofilament calcium sensitivity was determined by observing the isometric tension developed by challenging the bundles with pCa 7.2 compared with the maximal force developed by pCa 4.8. The sensitivity at pCa 7.2 is expressed as a percentage of this maximal force. The within-patient reproducibility of the myofilament calcium sensitivity is /10 %. We compared this calcium sensitivity with the clinical reaction in eight malignant hyperthermia susceptible probands (table 9). A blinded expert assigned a rank for severity of reaction. The Spearman rank correlation coefficient obtained between calcium sensitivity and rank order of reaction severity was 0.8095 (P  0.015). In a separate group of 13 patients tension produced at pCa 7.2 was shown to correlate with the percentage of type I muscle fibres

Proceedings of the Anaesthetic Research Society Table 9

Ca2 sensitivity and clinical reactions

Calcium Sensitivity at pCa 7.2 78 % 72 % 65 % 42 % 40 % 20 % 18 % 0%

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Onset of clinical reaction Wisdom teeth. End-tidal carbon dioxide 10kpa, heart rate 120 bpm on arrival in theatre Microlaryngoscopy. Masseter spasm worsening with further suxamethonium interfering with procedure Dental. Muscle rigidity and unable to insert mouth gag. Multiple ventricular ectopics. Procedure abandoned Tonsils. Progressive tachycardia during operation, end-tidal carbon dioxide 12 kPa, temperature 38 C axilla. Emergency LSCS. Masseter spasm, no hypermetabolism, next morning very stiff, myoglobinuria. Laryngoscopy. No intraoperative problems. Muscle aches and stiffness next day, myoglobinuria. Subtotal colectomy. Reaction on third operation of same day for rebleed after 5 h anaesthesia. Temp 39.7 C Total glossectomy and free flap, after 4 h tachycardia 160, end-tidal carbon dioxide 9.9, temp 39.6 C.

Table 10 Median rate of temperature rise during first 2 h ( C per h) (range) Group A (n  7) (Space blanket)

Rank order 1

Nasopharyngeal Rectal

4 Toe 2

Finger

Group B (n  5) (BairHugger)

0.85 0.30 (0 to 0.65) (0.70 to 1.15) 0.25 0.65 (0 to 0.65) (0.50 to 0.80)
1.45 0.65 (
2.85 to
0.50) (
0.55 to 4.00)
2.90 1.55 (
3.40 to
0.50) (
1.45 to 2.10)

3 7 5 8 6

obtained by using myosin ATPase stains (Pearson correlation coefficient r  0.7551, P  0.003). Myofilament calcium sensitivity of the malignant hyperthermia susceptible patients’ muscle correlates with the rapidity and severity of a malignant hyperthemia event. This probably reflects the muscle fibre type composition of the individual. Key words Anaesthetics. Complications, malignant hyperthermia. Model, skinned muscle fibre. Reference 1. Smith PD, Hopkins PM, Ellis FR, Halsall PJ. British Journal of Anaesthesia 1994; 73: 712P.

Convective warming combined with vasodilator therapy accelerates core rewarming after cardiac surgery S. J. HARRISON* AND J. PONTE Department of Anaesthetics, King’ College Hospital, London Perioperative hypothermia is associated with increased morbidity [1]. A drop in core temperature “after-drop” is frequently seen during the first 60–90 min after open heart surgery [2]. It has been claimed recently that convective warming is ineffective in accelerating body core rewarming in these patients [3], but without deliberate skin vasodilatation. Twelve patients undergoing elective cardiac surgery who had nasopharyngeal temperatures below 36 C on arrival to the intensive care unit were studied during the first 2 h after operation. Patients were randomized to receive either (a) Space blanket, or (b) BairHugger blanket connected to a BairHugger 275E power unit (high setting.) All patients received an infusion of glyceryl trinitrate 8–20 mg h1 and propofol 50–200 mg h1 and were mechanically ventilated. Shivering was suppressed using morphine, and vecuronium if required. Nasopharyngeal, rectal, toe and finger temperatures were monitored at 15-min intervals. The rate of temperature change during the first hour, second hour and both combined were compared between the two groups for all four measurement sites (Mann-Whitney U test). During the first 2 h the rate of increase in nasopharyngeal (P  0.01), rectal (P  0.05) and skin (P  0.01) temperature was greater in group B compared with group A (table 10). We, therefore, concluded that the BairHugger accelerated core rewarming in patients following cardiac surgery provided the stated dose of glyceryl trinitrate was used.

Key words Equipment, blankets. Temperature, body. References 1. Frank SM, Higgins MS. Anesthesiology 1995; 82: 83–93. 2. Noback CR, Tinker JH. Anesthesiology 1980; 53: 277–280. 3. Moors AH, Pickett JA. Woolman PS, Bethune DW, Duthie DJR. British Journal of Anaesthesia 1994; 73: 782–785.

Perioperatlve body temperature does not influence postanaesthetic shivering J. E. H. WARD* AND A. W. A. CROSSLEY Derby City General Hospital, Derby and the University Department of Anaesthesia, Queens Medical Centre, Nottingham In a study in young volunteers subjected to iatrogenic central hypothermia Sessler and colleagues [1] found that shivering after anaesthesia only occurred in hypothermic individuals. The results of this study are in contrast with a number of clinical studies in which body temperature has been found to correlate poorly with postoperative shivering [2]. We have re-examined the relationship between postoperative shivering and body heat by utilizing multiple site intraoperative temperature monitoring. We studied the perioperative temperature balance of 60 healthy patients undergoing a variety of procedures of at least 40-min duration. All received a standardized anaesthetic consisting of induction with thiopentone 3–4 mg kg
1, fentanyl 0.001–0.003 mg kg
1 and neuromuscular block with vecuronium 0.1 mg kg
1, followed by intermittent positive pressure ventilation to an end-tidal carbon dioxide concentration of 4–5 kPa with oxygen, nitrous oxide and enflurane to an end-tidal concentration of 1–2 %. During anaesthesia body temperature was measured with Yellow Springs series 400 thermistors (Yellow Springs Instruments, Ohio, USA) at seven skin sites and in the nasopharynx. The temperatures were logged every 2 min using an ESM9 data logger (Labdata Instrument Services Ltd, Carshalton, Surrey). On reversal of neuromuscular block the nasopharyngeal probe was removed while the skin recordings were continued throughout recovery where clinical evidence of shivering was sought. On the basis of accepted weighted formulas [3], mean skin temperatures were calculated (MST C  [0.07 head C]  [0.35 chest C][0.14 biceps C][0.05 hand C][0.19 thigh C][0.13 calf C][0.07 foot C]. Mean body temperatures were also calculated (MBT C  [0.66 core C] [0.33 MST C]), as was total body heat (TBHkJ  3.48 MBT body weight). Core to mean peripheral temperature (MPT C) gradients were also calculated. Sixty patients were entered into the study (31 females and 29 males); 25 exhibited some degree of shivering postoperatively, eight of whom shivered to a degree requiring treatment with pethidine 25 mg i.v. Those who shivered were not significantly different from those who did not with respect to age and length of operation. More men shivered than women (48.3 % compared with 35.5 %). There were no significant differences between those who shivered and those who did not with respect to mean skin temperature, mean body temperature or total body heat at any time during the procedure. There was a tendency for shivering patients to be peripherally cooler on induction of anaesthesia, with a larger core to peripheral gradient, although this failed to reach statistical significance (table 11).

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British Journal of Anaesthesia Table 11 (Mean skin temperatures (MST), mean body temperatures (MBT) and mean peripheral temperatures (MPT) (all in C) (95 % confidence limits) (n  60) Shiverers

Core MST MBT MPT Gradient

Non-shiverers

Induction

40 min

Reversal

Induction

40 min

Reversal

35.81 (0.31) 32.12 (0.32) 34.32 (0.23) 30.03 (0.58) 5.90 (0.64)

35.70 (0.32) 33.22 (0.35) 34.60 (0.29) 33.86 (0.31) 1.95 (0.31)

35.83 (0.14) 32.63 (0.42) 34.30 (0.34) 33.12 (0.36) 2.54 (0.37)

35.88 (0.22) 32.34 (0.22) 34.32 (0.10) 30.98 (0.43) 4.85 (0.49)

35.93 (0.21) 33.23 (0.36) 34.72 (0.18) 33.96 (0.23) 1.79 (0.40)

35.94 (0.24) 32.87 (0.31) 34.52 (0.21) 33.05 (0.46) 2.82 (0.45)

We have been unable to confirm the suggested relationship between core temperature and post-anaesthetic shivering [1], and our results were consistent with a number of other clinical studies. While the expression of postoperative shivering clearly mimicked thermogenic shivering, we suggest that the initiation of the phenomenon is not related to body temperature. Key words Temperature. Complications, shivering. References 1. Sessler DI, Rubinstein EH, Moayeri A. Anesthesiology 1991; 75: 594–610. 2. Crossley AWA. Anaesthesia 1992; 47: 193–195. 3. Ramanathan NL. Journal of Applied Physiology 1963; 19: 531–533.

Effects of anaesthetic drugs on dopamine release in a model of hypoxia and hypoglycaemia C. C. TONER AND J. A. STAMFORD Anaesthetics Unit (Neurotransmission Laboratory), London Hospital Medical College, London Attenuation of ischaemia-induced dopamine release in vivo has been shown to reduce neuronal cell damage [1]. We have found previously that ketamine delays, slows and reduces dopamine release occurring in an in vitro model of hypoxia and hypoglycaemia [2]. This effect is likely to be mediated via the antagonistic effects of ketamine at NMDA receptors although it could be an intrinsic property of anaesthetic drugs. In this study we have explored the effects of other common anaesthetic agents on dopamine release in the same model. An in vitro model was used in which rat striatal slices were superfused with an artificial CSF and subjected to “ischaemia” by removal of oxygen and reduction in glucose concentration from 4 to 2 mmol litre
1. “Real time” dopamine release was measured by fast cyclic voltammetry [3]. Four variables were measured; (a) the time to onset of dopamine release (Ton), (b) the rate of dopamine release ( [DA]), (c) the time to peak dopamine release (Tpk) and (d) the maximum dopamine release ([DA]max). Each drug-treated brain slice had a paired control from the same animal. All statistical comparisons were made by paired t test. In slices treated with thiopentone (600
mol litre
1), Ton was 124 (6) s, [DA] was 0.18 (0.04) ␮mol litre
1 s
1, Tpk was 185 (13) s and [DA]max was 31 (6)
mol litre
1 (means sem, n  5). The corresponding values for paired controls were Ton  176 (16) s (P  0.05 vs thiopentone), [DA] was 5.9 (1.6)
mol litre
1 s
1 (P  0.05), Tpk  28 (13) s (P  0,01) and [DA]max  104 (18) umol litre
1 (P  0.05). In slices treated with propofol (200
mol litre
1), Ton was 166 (7) s, [DA] was 0.98 (0.34) mol litre
1 s
1, 7pk was 72 (22) s and [DA]max was 41 (6) umol litre
1 (n  5). Corresponding values for paired controls were Ton  151 (7)s (P  0.05 vs propofol), [DA] was 2.9 (1.2)
mol litre
1 s
1 (not significant), Tpk  49 (19) s (P  0.05) and [DA]max  55 (12)
mol litre
1 (not significant). Midazolam (1
mol litre
1) and etomidate (10
mol litre
1) had no effect on any variable. Since etomidate had no effect on ischaemia-induced dopamine release, it is unlikely that neuroprotection in this model is an universal property of general anaesthetics. The lack of effect of midazolam suggested that GABAA receptors were not an important modulatory site of ischaemia-induced dopamine release. Propofol produced a modest delay in onset of dopamine release and a similarly moderate prolongation in time to peak dopamine

release. Thiopentone unexpectedly accelerated the onset of dopamine release while reducing the rate and amount. Further work is required to elucidate the mechanisms underlying these paradoxical effects. Key words Sympathetic nervous system, dopamine. Anaesthetics. Model, rat. Ischaemia. References 1. Buisson A, Callebert J, Mathieu E, Plotkine M, Boulu RG. Journal of Neurochemistry 1992; 59: 1153–1157. 2. Toner CC, Stamford JA. British Journal of Anaesthesia 1995; 75: 236P–237P. 3. Stamford JA. Journal of Neuroscience Methods 1990; 34: 67–72.

Survey of intensive care management of severely headinjured patients in the United Kingdom R. D. JEEVARATNAM* AND D. K. MENON Department of Anaesthesia, University of Cambridge and the MRC Centre for Brain Repair, Cambridge Secondary brain damage after head injury causes much avoidable death and disability, and the severity of such damage is affected directly by the quality of intensive care that such patients receive. Recent studies in the USA have shown wide variations in the intensive care management of severe head injury [1], but comparable data from the UK are not available. This study reports on current practice in the intensive care management-of patients with severe head injury in neurosurgical referral centres in Great Britain and Ireland. We undertook structured telephone interview of ICU sisters, senior staff nurses or clinical nurse specialists in adult neurosurgical referral centres in the United Kingdom. All 39 adult neurosurgical centres identified using information obtained from the Medical Directory and professional bodies were surveyed successfully. Data regarding the organization and administration of intensive care services and patterns of monitoring and treatment were recorded. Data reliability was assessed by resurveying 20 randomly selected centres ( 50 %). Patients with severe head injury were managed on specialist neurosurgical ICUs in 54 % of neurosurgical centres, and on general ICUs in the remainder. Their intensive care was coordinated by an anaesthetist in 64 % of instances and by a neurosurgeon in 30 %. Annual caseload varied between units, with 51 % receiving 100 patients, 30 % receiving 50–100 patients and the remainder receiving less than 25 patients a year. There was considerable variability in both monitoring and therapy between centres. Invasive arterial pressure monitoring was used routinely in 92 % of centres, but central venous pressure monitoring was used routinely in only 62 % of centres, and ICP was monitored routinely in only 49 % of centres. Corticosteroids were used to treat intracranial hypertension in 49 % of centres. Of the centres studied, 43 % routinely aimed for PaCO2 values between 3.3–4.0 kPa, and hyperventilation to PaCO2 of less than 3.3 kPa continues to be used in at least one centre. Neuromuscular block was used routinely in 66 % of centres. Both propofol and midazolam were commonly used (64 % for both agents). There were wide variations in the intensive care management of acute head injuries in the centres surveyed. Treatment modalities such as severe hypocapnia and steroid therapy continued to be used despite evidence of their inefficacy or dangers [2, 3]. Rationalization of the intensive care management of severe head

Proceedings of the Anaesthetic Research Society

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injury, with the incorporation of new research findings into standard management protocols, is likely to result in an improvement in the quality of care.

Haematocrit, end-tidal isoflurane and carbon dioxide concentrations appeared relatively unimportant.

Key words Head, injury. Brain, intracranial pressure. Ventilation hyperventilation. Hormones, corticosteroids.

Key words Liver, blood flow. Equipment, lasers.

References 1. Ghajar J, Hariri RJ, Narayan RK, Iacono LA, Firlik K, Patterson RH. Critical Care Medicine 1995; 23: 560–567. 2. Cold GE. Acta Neurochirugica (Wien) 1989; 96: 100–106. 3. Gudeman SK, Miller JD, Becker DP. Journal of Neurosurgery 1979; 51: 301–306.

Actions of isoflurane and halothane on whole cell calcium and potassium currents in cultured, identified, mollusc neurones

Liver microcirculation during major surgery in humans H. O’BEIRNE*, P. J. GUILLOU* AND M. C. BELLAMY Department of Anaesthesia and Surgery, St James’s University Hospital, Leeds Most studies on hepatic microcirculation have used microsphere techniques in animals. Relatively little is known of the factors governing intraoperative liver blood flow in humans. We have, therefore, studied effects of anaesthesia, extradural block and dopamine on hepatic microcirculatory flow during major surgery in humans by a non-invasive technique. Ethics Committee approval was obtained. Fifteen adult patients undergoing major upper abdominal surgery gave informed consent. After premedication with temazepam 20 mg, anaesthesia was induced with thiopentone 3 mg kg
1 and fentanyl 3
g kg
1. Neuromuscular block was facilitated by infusion of atracurium. The lungs were ventilated with isoflurane in oxygenenriched air. An extradural catheter was sited at T7–8. After abdominal incision, steady-state liver blood flow (LBF) in segment 3 was assessed by laser Doppler flowmetry. The measurement was repeated after surgical handling of viscera. Bupivacaine 50 mg was injected extradurally, and LBF measured at 15 min. Dopamine 3
g kg
1 min
1 i.v. was begun, and LBF assessed after 15 min. Trends in LBF were plotted. The following were entered into a regression model to predict LBF: age, weight, haematocrit, end-tidal carbon dioxide, end-tidal isoflurane concentration, presence of extradural block, surgical handling, presence of dopamine infusion, mean arterial pressure and central venous pressure. A trend in LBF with operative stage was noted (P  0.003, Kruskall Wallis, fig. 4). In particular, LBF was markedly reduced in the presence of extradural block, but was restored by dopamine. Multiple regression showed only two predictors of LBF. These were MAP and CVP. The difference MAP-CVP (perfusion pressure) was highly correlated with LBF, r2  0.41, P  0.0009). We have studied LBF in patients undergoing major abdominal surgery. The major determinant was perfusion pressure. Extradural block and low-dose dopamine exerted their effect on LBF apparently through changes in perfusion pressure.

H. F. MOGHADAM* AND W. WINLOW Department of Physiology, University of Leeds, Leeds Anaesthetics depress neuronal excitability, as is evident from the reduction in spontaneous and synaptically-evoked firing that they induce. Recently, halothane has been shown to decrease calcium currents in the pedal I cluster neurones of Lymnaea [1]. Here we examined the effects of halothane and isoflurane on calcium and potassium currents in cultured pedal I cluster neurones of the pond snail Lymnaea stagnalis using the whole cell patch-clamp technique. Neurones were prepared as described previously [1] as were bath and pipette solutions [2] except that calcium rather than barium was used as the charge carrier for calcium currents. Isoflurane (2 %) diminished inward calcium currents in pedal I cluster neurones. The neurones (n  6) were clamped at
50 mV and depolarized from
90 to 90 mV in 10-mV steps every 10 s. These results are consistent with our previous data using halothane [1]. The effects of 2 % halothane on gross potassium currents are shown in figure 5. Similar effects were obtained with 2 % isoflurane. There is controversy about the effects of anaesthetics on potassium currents. Franks and Lieb [3] have shown that the volatile anaesthetics halothane and isoflurane activate novel neural potassium currents in the ventral neurones of the parietal ganglion of Lymnaea, using two electrode voltage clamp. Here we showed that both halothane and isoflurane (2 %) inhibited potassium currents in the pedal I cluster neurones. These differences may be due to very different types of potassium channels in the distinct cell types used by us compared with those used by Franks and Lieb [3] or to the fact that we used isolated neurones in the absence of synaptic or trophic influences.

Key words Model, mollusc. Ions, potassium. Anaesthetics volatile, isoflurane. Ions, calcium, halothane

Acknowledgement H.F.M. is supported by an Iranian government scholarship. References 1. Yar T, Winiow W. Journal of Physiology 1993; 459: 12P. 2. Moghadam HF, Winlow W. Journal of Physiology 1995 (in press). 3. Franks NP, Lieb WR. Nature 1988; 333: 662–664.

Method for voltage clamping cut fibres of human skeletal muscle T. J. MORRIS, P. M. HOPKINS AND W. WINLOW Departments of Physiology and Anaesthesia, University of Leeds

Figure 4 Liver blood flow trends (mean and SEM). P  0.003 (Kruskall-Wallis).

The fibrous surface layer of non-neonate skeletal muscle often precludes the use of large diameter microelectrodes in voltageclamp investigations unless the cell membrane is pretreated or the cells disrupted and cultured into so-called myotubes. A technique has been devised that will minimize cell disruption using a two-electrode configuration of voltage clamp in a comparative study of sarcolemmal currents from normal and malignant hyperthermia susceptible humans. Pieces of muscle from open biopsies of vastus internus were stretched and pinned out in a continuous perfusion of car-

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British Journal of Anaesthesia

Figure 5 Effects of 2 % halothane on potassium currents on pedal I cluster neurones of Lymnaea. Control data obtained in standard bath solution; 2 % halothane data obtained within 3 s of adding halothane saline; the 5-min data were recorded 5 min later during continuous 2 % halothane perfusion. The preparation was then washed-in standard bath solution (wash) and finally 1 mmol litre
1 CdC12 was applied in bath solution to block calciumdependent potassium currents. ( ) Control; ( ) 2 % halothane; ( ) 5 min; (
) wash; (*) 1 mmol litre
1 CdCl2. boxygenated Lily’s solution at 20 C. The cut fibres within this preparation were believed to reseal [1] and so were presumed to be electrically finite in length. Superficial fibres were selected and easily penetrated with glass microelectrodes bevelled to between 2 and 5 M [2]. A space clamp was achieved with an interelectrode gap of less than 50
m to minimize non-uniformities of membrane potential through cable effects, The bath potential was measured by a third electrode and subtracted automatically from the voltage signal. Measured cell variables were (mean (SEM)): length 33 (2) mm (n  10); resting potential
42 (2.6) mV (n  42); input resistance 337.6 (19.8) k (n  34); charging time constant () 3.27 (0.30) ms (n  34). During experiments a chloride-free bathing solution containing the anionic blocker anthracene-9carboxylic acid was used. This increased input resistance to 854.2 (47.0) k (n  35) and  to 17.0 (1.3) ms (n  34). Stepped changes in voltage clamp potential stabilized in less than 0.5 ms, giving a minimum recording resolution of 2.5 ms. This was satisfactory as experiments were aimed at isolating voltage-gated calcium currents shown to activate over tens or hundreds of milliseconds [3].

Acknowledgement This work was supported by an MRC grant to P.M.H. and. W: W. T. J. M. is supported by an EC international collboration grant to W.W. References 1. Lehmann-Horn F, Iaizzo PA. Muscle and Nerve 1990; 13: 222–231. 2. Lederer WJ, Spindler AJ, Eisner DA. Pflugers Archiv 1979; 381: 287–288. 3. Beam KG, Knudson MC. Journal of General Physiology 1988; 91: 799–815.


2-opioid receptors couple to phospholipase C in SH-SY5Y human neuroblastoma cells D. SMART AND D. G. LAMBERT University Department of Anaesthesia, Leicester Royal Infirmary, Leicester Tyr-D-Arg2-Phe-sarcosine4 (TAPS) is an analogue of dermorphin which acts as a
1-opioid agonist, but as. a
2-opipid antagonist, in rats in vivo [1]. We have demonstrated-previously in SH-SY5Y cells that
-opioids couple to phoipholipase C (PLC) and so increase inositol(l,4,5)triphosphate (Ins(l,4,5)P3) formation [2]. Furthermore, these
-receptors bind naloxonazine reversibly [3], indicating they are of the
2-opioid subtype. Thus, we have used TAPS to confirm the subtype of the PLC-coupled
-opioid receptor. Whole cell suspensions (0.3 ml) in Krebs/HEPES buffer, pH 7.4, were preincubated at 37 C for 15 min, with or without TAPS 1 nmol l
1–10
mol l
1. The cells were then incubated

Figure 6 (A) Currents elicited from voltage clamped human skeletal muscle during the stepped depolarizations indicated in mV. (B) Current amplitude at 200 ms plotted against command voltage. Figure 6A shows currents recorded during stepped depolarizations from a holding potential of
90 mV. The recording solution included potassium channel blockers tetraethylammonium (150 mmol litre
1) and 4-aminopyridine (1 mmol litre
1) and calcium at 2 mmol litre
1. The I-V curve (fig 6B) shows an inward current activating at
70 mV, reaching a peak at
30 mV and reversing at 25 mV. This inward peak reduced substantially in the presence of nifedipine and might therefore be composed partly of calcium components. Key words Complications, malignant hyperthermia. Muscle, skeletal.

Table 12 Effect of TAPS on peak fentanyl-induced Ins(l,4,5)P3 formation in SH-SY5Y cells. (Mean (SEM) (n  5). Whole curve P  0.05 by ANOVA. *P  0.05 decreased compared with fentanyl alone) Ins(l,4,5)P3 (pmol/mg protein) Basal Fentanyl 0.1
mol litre
1 TAPS 10
mol litre
1 TAPS 1
mol litre
1 TAPS 0.1
mol litre
1 TAPS 10 nmol litre
1 TAPS 1 nmol litre
1

6.3 (0.5) 24.0 (1.0) 6.2 (0.7)* 6.3 (0.8)* 9.7 (1.0)* 16.7 (1.1)* 22.9 (1.1)

Proceedings of the Anaesthetic Research Society with fentanyl 0.1
mol litre
1 or TAPS 1
mol litre
1 for 0–300 s. Ins(l,4,5)P3 was assayed as described previously [2]. Statistical comparisons were made by ANOVA and/or Student’s t test. Fentanyl 0.1
mol litre
1 caused a monophasic increase in Ins(l,4,5)P3 formation, which peaked (24.9(1.9) pmolmg
1 protein, n  5) at 15 s and returned to basal concentrations between 1 and 2 min, as previously reported [2], TAPS had no effect on basal, but dose-dependently inhibited fentanyl-induced, Ins(l,4,5)P3 formation (table 12). Half maximal inhibition occurred at 16.0(0.9)
mol litre
1, consistent with TAPS acting at the ␮2-opioid receptor [1], In conclusion,
2-opioid receptors couple to PLC in SH-SY5Y cells. Key words Anaesthetics opioid,
-opioids. Pharmacology, inositol(l,4,5)triphosphate. Model, SH-SY5Y cells. Acknowledgement Financial support by the Wellcome Trust is gratefully acknowledged. References 1. Paakkari P, Paakkari I, Vonhof S, Feurstein G, Siren AL. Journal of Pharmacology and Experimental Therapeutics 1993; 266: 544–550. 2. Smart D, Smith G, Lambert DG. Biochemical Journal 1995; 305: 577–582. 3. Elliott J, Smart D, Lambert DG, Traynor JR. European Journal of Pharmacology : Molecular Pharmacology 1994; 268: 447–450 Enflurane reduces potassium-stimulated release of acetylcholine from rat cortical slices C. ELTON*, J. GRIEFF, R. CARANZA*, R. GRIFFITHS, R. I. NORMAN AND D. J. ROWBOTHAM Department of Anaesthesia and Medicine, Leicester Royal Infirmary, Leicester Acetylcholine is an excitatory neurotransmitter that has been implicated in arousal [1]. We have demonstrated previously that halothane, in clinical doses, significantly reduced potassiumevoked acetylcholine release from rat cortical slices [2]. This study was designed to investigate whether enflurane also produced this effect. Brain cortical slices (350
m) were prepared from female Wistar rats and divided into two equal aliquots. One aliquot was incubated in oxygenated Krebs buffer, the other in oxygenated

663P Krebs buffer containing 65
mol litre
1 phospholine (organophosphorous anticholinesterase), both at 37 C for 10 min. These slices were then incubated with Krebs buffer containing potassium, either 5 or 46 mmol litre
1, which had been preequilibrated with carrier gas (95 % oxygen, 5 % carbon dioxide) or carrier gas containing enflurane at partial pressures from 0.2 to 5 %. At 0 and 30 min samples were centrifuged and the supernatants assayed for acetylcholine content using a chemiluminescent assay [3]. At all concentrations tested enflurane markedly reduced acetylcholine release (P  0.05, paired t test). Anomalously, low concentrations of enflurane (up to 0.6 %) were more effective than higher concentrations (1–5 % (Fig. 7)). This was in contrast with halothane which produced a dose-dependent inhibition of acetylcholine release. The current results suggest a complex action of enflurane on acetylcholine release.

Key words Nerve, neurotransmitters, acetylcholine. Anaesthesia. Ions, potassium. Model, rat.

References 1. Kanai T, Szerb JC. Nature 1965; 205: 80–82. 2. Griffiths R, Greiff JMC, Haycock D, Elton C, Rowbotham DJ, Norman RI. British Journal of Pharmacology 1995 (in press). 3. Isreal M, Lesbats B. Neurochemistry International 1981; 3: 81–90. Observations on muscle temperature changes during cardiopulmonary bypass J. JOHNSON*, J. DESAI* and J. PONTE Departments of Anaesthetics and Cardiothoracic Surgery, King’s College Hospital, London It has been proposed that vasoconstriction of vascular beds during the warming phase of cardiopulmonary bypass (CPB) is the cause of the postoperative “after-drop” in core temperature [1]. Skeletal muscle accounts for 40–45 % of the total body mass in non-obese subjects and its blood supply is capable of large relative changes. Changes in muscle temperature associated with CPB have received relatively little attention in the past. Temperature readings were collected each minute during CPB from 14 consecutive patients (11 male) admitted for coronary artery grafts (also aortic valve replacement in two patients) aged 46–71 yr, weighing 60–106 kg. Thermocouple probes were placed routinely in the nasopharynx (NPT), into the quadriceps muscle (QMT, 4cm from skin) and in the arterial and venous perfusion cannulas. Induction and maintenance of anaesthesia was with propofol infusion, fentanyl 1.5–2 mg and a vecuronium bolus of 6–8 mg. Phenylephrine was used to maintain arterial blood pressure at 60 mm Hg during CPB. Nitroglycerine and inotropes were not used during CPB. Patients were cooled to a nasopharyngeal temperature (means (SD)) of 32.03 (0.36) C and CPB lasted 53–114 min. Sixteen min after rewarming started, NPT increased to 37.25 (0.66) C and QMT to 32.91 (1.2) C (from 31.93 (0.68)). After bypass, NPT steadily declined as illustrated in figure 8 and QMT continued to increase at a slower rate. Changes in quadriceps muscle temperature lagged considerably compared with those in the nasopharynx. Pharmacological vasodilatation of skeletal muscle might be indicated to accelerate its rewarming at the end of CPB. Key words Heart, cardiopulmonary bypass. Muscle skeletal. Temperature, body.

Figure 7 n  5 for all values except 0.6, 1 and 5 % where n  6. (Error bars are SEM).

Reference 1. Noback CR, Tinker JH. Anesthesiology 1980; 53: 277–280.

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British Journal of Anaesthesia

Figure 8 blood.

Temperature changes during CPB observed in one patient. (
) Muscle; ( ) nasopharynx; (!) arterial

We concluded that midazolam when combined with alfentanil, reduced significantly the dose of propofol required for induction and improved the conditions for LMA insertion.

Midazolam before induction improves conditions for laryngeal mask insertion I. DRIVER*, S. WILTSHIRE*, P. MILLS*, N. LILLYWHITE* AND R. HOWARD-GRIFFIN* Department of Anaesthesia, Ipswich Hospital, Ipswich Successful insertion of a laryngeal mask airway (LMA) requires adequate mouth opening and suppression of upper airway reflexes to prevent coughing, gagging and laryngeal spasm. Previous studies have demonstrated that these conditions are best provided by propofol [1, 2]. The induction dose of propofol may be significantly reduced if combined with alfentanil and midazolam [3]. In this study we investigated the effect of alfentanil, and midazolam/alfentanil combination on propofol requirements and conditions for LMA insertion. Ninety unpremedicated healthy patients (aged 16–55 yr) were allocated randomly to one of three groups: group 1 received propofol only 2.5 mg kg
1, group 2 received alfentanil 10
g kg
1 90 s preinduction followed by propofol 2.5 mg kg
1, Group 3 received midazolam 0.04 mg kg
1 3 min preinduction and alfentanil 10
g kg
1 90 s preinduction followed by propofol 1.25 mg kg
1. Thirty seconds after the propofol, the adequacy of anaesthesia was assessed by the “blinded” anaesthetist. If adequate, the mouth was opened and LMA insertion attempted. If inadequate, further boluses of propofol could be requested by the anaesthetist (0.25 mg kg
1 every 15 s). We assessed mouth opening (fully relaxed, some resistance or impossible), the ease of LMA insertion (easy, some difficulty, difficult or impossible) and any undesired responses to LMA insertion. The total dose of propofol for adequate anaesthesia was noted. Data were analysed using one-factor ANOVA and chisquare as appropriate. A P value 0.05 was considered statistically significant. The main findings are shown in table 13. There was no significant difference between the groups in age, height or weight. Patients in the midazolamalfentanil group required significantly less propofol, had better mouth opening and fewer undesired responses to LMA insertion than the other two groups.

Table 13

Keywords Anaesthesia, general. Equipment, laryngeal mask. Anaesthetics i.v., propofol. References 1. Scanlon P, Carey M, Power M, Kirby F. Canadian Journal of Anaesthesia 1993; 40: 816–818. 2. McKeating K, Bali M, Dundee JW. Anaesthesia 1988; 43: 638–640. 3. Vinik HR, Bradley EL, Kissin I. Anesthesia and Analgesia 1994; 78: 354–358.

Laryngeal mask airway—optimum time for insertion ? B. KINIRONS*, K. HUBBARD* AND A. J. CUNNINGHAM Department of Anaesthesia, Beaumont Hospital, Dublin, Ireland Airway complications associated with laryngeal mask airway (LMA) placement have been well documented [1]. The choice of both anaesthetic induction agent and timing of LMA placement are important clinical considerations. The objectives of the study Table 14

Patient response to LMA insertion. *P  0.05

Apnoea Cough Laryngospasm Bronchospasm SaO2  90 %

Group A (n  50)

Group B (n  50)

46 (92 %) 7 (14 %)* 1 (2.5 %) 0 7 (14 %)*

45 (90 %) 3 (6 %) 3 (6 %) 0 2 (4 %)

Observations by study anaesthetist and total propofol requirement for loss of eyelash reflex (mzean (SD))

Eyelash reflex lost with initial dose Mouth fully relaxed LMA insertion easy No response to insertion Propofol mg kg
1

Group 1 (n  30)

Group 2 (n  30)

Group 3 (n  30)

14 21 28 6 3.12 (0.66)

6 15 21 14 2.16 (0.67)

26 30 30 27 1.29 (0.13)

P value 0.0001 0.0006 0.001 0.0001 0.0001

Proceedings of the Anaesthetic Research Society were to compare two techniques for LMA insertion and to document the incidence of respiratory complications associated with its placement following propofol induction of anaesthesia. After institutional Ethics Committee approval 100 ASA I-II patients scheduled for elective ambulatory surgical procedures were anaesthetized with fentanyl 1
g kg
1, propofol 2.5 mg kg
1, 50 % nitrous oxide in oxygen and 0.5–2 % isoflurane. All patients were preoxygenated with 100 % oxygen for 3 min before induction. Patients were randomized into two groups. In group A (n  50) the LMA was placed immediately after induction whereas patients in group B (n  50) had assisted ventilation for 2 min with 50 % nitrous oxide in oxygen and 2 % isoflurane before LMA placement. An independent observer recorded the absence or presence of the following respiratory complications: apnoea, cough, laryngospasm, bronchospasm and desaturation ( SaO2  90 %). If present the respiratory complication was graded according to a severity scale [2]. Additional information recorded included the number of attempts at LMA insertion, heart rate and SaO2 . Data were recorded every 15 s for a total period of 5 min after LMA placement. The data were analysed using chi-square test. Some of the results are shown in table 14. Early LMA insertion following propofol induction was associated with a significantly

665P higher incidence of coughing (14 % vs 6 %) and SaO2  90 % (14 % vs 4 %) when compared with the delayed insertion. The laryngeal mask instruction manual recommends immediate insertion of the LMA after induction with propofol [3]. Data from our study suggested that delayed insertion was preferable in order to minimize airway complications associated with LMA placement. Key words Equipment, laryngeal mask. Complications, respiratory. Airway. Acknowledgement This study was facilitated by the Charitable Infirmary charity trust. References 1. Scanlon P, Carey M, Power M, Kirby F. Canadian Journal of Anaesthesia 1993; 40: 816–818. 2. Cregg N, Wall C, Mannion D, Green D, Casey W. British Journal of Anaesthesia 1995; 74(S1): 95–96. 3. Brain AIJ. The Intravent Laryngeal Mask Instruction Manual, 2nd Ed. Brain Medical Limited, 1992.