PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY

Br. J. Anaesth. (1984), 56,1279P

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY EDINBURGH MEETING JUNE 30,1984 (* Indicates non-member. The name of the author presenting the paper is in bold type.)

F. A. WALI

Anatsthaics Unit, TTu London Hospital Medical College, Whaeckaptl, London In addition to its central effect, diazepam also has a peripheral action and produces relaxation of skeletal muscle. Although the effects and interactions of diazepam at the skeletal muscle have been studied, the results obtained are controversial (Hamilton, 1967; Dretchen, Ghoneim and Long, 1971; Khan and Edman, 1983). For example, Hamilton (1967) showed that diazepam produced inhibition of both directly and indirectly elicited twitch contraction and this action was often preceded by a potentiation of the muscle twitch. Other workers (Dretchen, Ghoneim and Long, 1971; Khan and Edman, 1983) showed that diazepam either increased or decreased twitch contractions without initial stimulation. The aim of the present experiments was to study the pharmacological actions and interactions of diazepam with neuromuscular blocking agents and cholinergic agonists in the rat diaphragm and chick biventer cervkis skeletal muscle to see if diazepam altered the contractile responses produced by motor nerve stimulation and by cholinergic drugs. The preparations were set up in organ baths containing Krebs-Henseleit solution maintained at 38±2°C and bubbled with 5% carbon dioxide in oxygen. The contractile responses produced by electrical and chemical stimulation were recorded isometrically using a force displacement transducer and a Washington pen recorder. Diazepam 3.4-340junol litre"1 produced a dose-dependent increase in the twitch contractions elicited at 0.2 Hz in response to nerve stimulation in the rat and chick skeletal muscle. Diazepam 340 fimol litre"1 increased the twitches of the chick by 23 ±0.9% and the rat by 28±0.5%(mean±SEM, n = 6, P<0.001). However, diazepam 340 \tmo\ litre"1 had no n:gnif;rTinr effect on the tetanic contractions elicited at 1-100 Hz in the rat diaphragm. In addition, there was no significant interaction between diazepam and the neuromuscular blocking drugs, tubocurarine 1.27 funol litre"1, atracurium 1 funol litre"1 and suxamethonium lumollitre" 1 . High concentrations of diazepam (SOOpunol litre"1) decreased the twitch contractions and reduced 1 the contractures produced by ACh 0.5-55umollitre" or TEA 1.2-12 mmol litre"1 by 30-60% in the chick skeletal muscle. Although the mechanism by which diazepam potentiates the twitch tension is not yet known, Khan and Edman (1983) attributed this action to an effect by diazepam on intracellular calcium ions (release of activator calcium). In conclusion, the present experiments showed that diazepam in low concentrations increased the twitch contractions and in

high concentrations reduced the twitch and the contractures produced by ACh and TEA in the chick skeletal muscle. REFERENCES

Dretchen, K., Ghoneim, M. M., and Long, J. P. (1971). Anesthtsiology, 34,463. Hamilton, J. T. (1967). Can. J. Physiol. Pharmacol, 45,191. Khan, A. R., and Edman, K. A. P. (1983). Acta Physiol. Scand., 117, 533.

A COMPARISON OF DIAZEPAM AND MIDAZOLAM AS SEDATIVES FOR MINOR ORAL SURGERY A. M. SKBLLY*, M. J. BOSCOE*, S. DAWLTNG* AND A. ADAMS

P.

Dtpartmtntx of Anaesthetics, Clinical Dtntal Surgtry Guy's Hospital Medical & Dental Schools (Unittd Medical Schools), University ofLondon Minor oral surgical procedures performed on outpatients may be stressful, particularly where multiple local analgrsic blocks are necessary. Sedation with benzodiazepines i.v. can render such procedures acceptable. We compared diazepam in propylene gtycol (Valium:Roche) with midazolam (Hypnovel:Roche) as sedatives in 40 patients (ASA class I and H) undergoing the removal of third molar teeth. The purpose of the study was to assess whether the theoretical and reported advantages of miHo-mlgm over diazepam were borne out clinically. These include good quality sedation with excellent local tolerance, profound anterograde amnesia and rapid recovery. Ethics committee approval and written informed consent were obtained, and the patients randomly allocated to receive either diazepam or midazolam. Investigations included blind assessments by dentists and patients; heart rate and arterial pressure recordings every 3min during sedation and surgery; repeated testing of psychomotor and cognitive function and serum benzodiazepine measurements, each for 5h after sedation, and assessment of venous sequelae at 7 days. After completing six baseline recovery tests, 20 patients received each sedative under standard conditions via the Cardiff Palhator mfusor at 5mgmin"' for diazepam and 2.5mgmin" 1 for midazolam. The infusion was stopped in each patient on the decision of the same investigator, who, unaware of which drug was in use, deemed sedation to be adequate when the patients were unable to open their eyes actively against a ptosis to the level of the pupil. After establishment of sedation, the surgery was conducted routinely, all patients receiving local analgesia with 2% lignocaine with adrenaline 1:80 000. The groups were well matched (table I).

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ACTIONS AND INTERACTIONS OFDIAZEPAM AT THE CHICK AND RAT SKELETAL MUSCLE

BRITISH JOURNAL OF ANAESTHESIA

1280P TABLE I. Details of patients ttudied Age(yr) n

Mean

Weight (kg)

Op. time

and his colleagues (1983). The explanation for this is unclear, but may be related to variations in tissue binding of the two preparations. REFERENCES

SD Mean SD Mean SD

Diazepam

20

21.7

(3.3) 64.6 (12.5) 39.6 (17.9)

Midazolam

20

21.7

(2.5) 66.3 (13.1) 40.4 (13.4)

PLASMA DIAZEPAM CONCENTRATIONS FOLLOWING VALIUM AND DIAZEMULS I.V. J. P. H. FEE, J. W. DUNDEE, E. MCCLEAN, P. S. COLLIER

Departments of Anaesthetics and Pharmacy, The Queen's University of Belfast Because it causes less pain on injection and less venous thrombosis, the emulsion form of i. v. diazepam (Diazemuls) has largely replaced the organic solution (Valium) in Hiriinil practice. Although it is assumed generally that these two preparations are equivalent in potency, Dundee and Kawar (1982) reported significantly higher plasma diazepam concentrations with Valium 10 mg than with Diazemuls 10 mg when given by deep i.m. injection. Dental surgeons have commented on the lesser potency of the latter, and we report a within-subject cross-over itudy of plasma concentrations in volunteers given 10 mg of each preparation i.v. in random order at intervals of not less than 3 weeks. Seven subjects (five male) took part in the study. Venous blood was sampled at frequent intervals for 24 h and plasma diazepam concentrations were measured by GLC. Mean plasma diazepam concentrations (± SEM) at 5 min were 684±67ngml-' for Valium and495±47ngml- 1 for Diazemuls: at 15min 500±29ngml-' for Valium and 389±37ngml-' for Diazemuls. These differ significantly at the 5% level. This trend continued throughout, differences being significant at 7 and 12 h after injection. This is reflected in the mean AUC24 of 2892±226ng ml"'h" 1 for Valium compared with 2315± 192ng m l - ' h - ' for Diazemuls, the difference between these being highly significant (i>< 0.001). These finding* are in agreement with clinical observations by Gjessing and Tomlin (1977) and with the finding* of von Dardd

CONTRIBUTION OF EXPIRATORY MUSCLE ACTIVITY TO VENTILATION DURING ANAESTHESIA G . B. DSUMMOND, W. J. MCCULLOCH* AND D . T . BROWN*

Department of Anaesthetics, Royal Infirmary, Edinburgh Expiratory activity in the abdominal muscles has been a common observation during anaesthesia (Freund, Rood and Dodd, 1964). Airway occlusion during expiration was applied to nine patients during enflurane and nitrous oxide anaesthesia to assess the infliimrr of expiratory muscle activity (EMA) on ventilation. Intragastric pressure was measured using a gastric balloon, and ventilation using a pneumotachograph. Wf r-alnilarrd i-lopnrwf nf thf nmpirnrnry «yprm hy mcamiring tidal volume, and the pressure generated in the airway when the subsequent expiration was occluded (OE). Three out of nine patients had clinically obvious EMA. In these patients, intragastric pressure decreased at the start of inspiration (fig. 1), and in these subjects the respiratory elastance calculated from airway pressure during occluded expiration was significantly greater than the elastance measured during neuromuscular blockade and artificial ventilation. The mean airway pressure during OE was 43% greater than the pressure expected in these subjects, if there had been no EMA. From measurements of inspiratory occlusion pressure, we calculate that this increased expiratory pressure would contribute at least 19% to the tidal volume. Positive end-expiratory pressure did not stimulate or augment EMA.

S 7 - 1OI

Fio. 1. Typical tracing of airway flow pressure and gastric pressure during an occluded expiration. The dotted line indicates the expected airway pressure, calculated from the elastance measured during paralysis. REFERENCE

Freund, F., Rood, A., and Dodd, R. B. (1964). / . Appl. Physiol., 19,693.

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Both drugs were acceptable to dentists and patients and neither caused significant cardiovascular or respiratory depression. On titratkra as described, the mean dose of midazolam to diazepam was in the ratio 1:2.02. More amnesia was found in the midazolam group and more venous Hamngi- at sites of drug infusion in the diazepam group, although the differences were not statistically significant. Midazolam or diazepam were detectable in the final serum samples from ajl subjects. Nordiazepam concentrations increased in all but one patient in the diazepam group and 81% of patients showed increasing diazepam concentrations after 200 min. Recovery profiles were nimilar for both drugs. Only one test showed the midazolam group to recover sooner. Delayed memory recall was significantly impaired (P<0.001) in both groups at 1,3, and 5 h after sedation. We conclude that the advantages claimed for midazolam are confirmed, but the recovery is not necessarily faster than after diazepam over the first 5h.

von Dardd, O., Mebius, C , Mossberg, T., and Svensson, B. (1983). Br. J. Anatsth., 55,41. Dundee, J. W., and Kawar, P. (1982). In Pharmacology of Benmodiaxepines (eds E. Usdin, P. Skolnkk, J. R. TaUman jr, D. Greenblatt and S. M. Paul), p.313. London: Maanillan. Gjessing, J., and Tomlin, P. J. (1977). Br. J. Anaesth., 49, 954.

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY EFFECT OF POSITIVE EXPIRATORY PRESSURE ON EXPIRATORY DURATION DURING ENFLURANE ANAESTHESIA W. J. MCCUIXOCH,* G. B. DRUMMOND AND D. T. BROWN*

Department ofAnaesthetics, Royal Infirmary, Edinburgh

FIG. 2. Relationship between lung volume and mean duration of inspiration for normal (open symbols) and occluded (closed symbols) breaths with and without PEEP (round and square symbols respectively) in the patients studied. REFERENCES

Drummond, G. B. (1984). Br. J. Anaath., 56, 215. Polacheck, J., Strong, R., Arens, J., Dimes, C , Metcalf, I., and Younes, M. (1980). / . Appl. Physiol., 49,609.

INTRAVENOUS NUTRITION IN INTENSIVE CARE: A ROLE FOR THE MICROCOMPUTER M. WALKEB,* C. AUSTIN AND D. E. R. BURT

Research Dtpartmtnt of Anaesthetics, St Andruw's Hospital, Boa, London Intravenous nutrition for the patient in the Intensive Care Unit (ICU) presents many problems. In addition to providing appropriate metabolic requirements account must be taken of excessive

losses of Quid and electrolytes from such diverse sources as intestinal fistulae, surgical drains, sweating and the respiratory tract. These losses are not constant, but tend to fluctuate and increase the difficulty in maintaining effective fluid and electrolyte balance. To compile a list of all fluid and electrolyte losses and to incorporate these into a suitable regimen is a tedious and time-consuming task which is often performed ineffectively. It is, however, a task to which a microcomputer is well suited. A program to astist in the management of i.v. feeding and fluid balance of patients in the ICU has been devised and written for the Apple II microcomputer. The program consists of four parts: (A) Details of each patient and the feeding solutions available are stored on file. (B) The program is run for each patient once a day. Different sources of fluid and electrolyte lost are identified on a patient profile table, and the 24-h volumes of these sources (and their electrolyte contents if analysed) are entered from the keyboard. Insensible losses are estimated from the patient's temperature and degree of sweating. Details of the previous 24-h total volume and electrolyte outputs, and estimated nitrogen and energy requirements are displayed. These outputs may be accepted as they stand to form the target feeding requirements, or altered in the light of available serum electrolyte analysis. (C) Based on these requirements and the available algorithm the computer will create and display the feeding regimen which matches the target most closely. A table of components required and components offered is displayed to enable the regimen to be checked for discrepancies. A print-out of both regimen and table is available, and the data are stored on disc. A n-nrhing feature is incorporated, allowing the operator to create his own feeding regimen and to examine the discrepancies that thin produces. (D) The fluid and electrolyte halanry of the patient over the entire feeding period may be examined graphically or in tabular form. By removing large amounts of tedious calculation and allowing clear and concise displays of fluid and electrolyte balance, it is anticipated that this program will assist the clinician in the more effective feeding of patients in the ICU.

THE INCIDENCE OF CARDIAC ARRHYTHMIA DURING ANAESTHESIA FOR DENTAL EXTRACTIONS: HALOTHANE AND ISOFLURANE COMPARED W. R. CASSON*, R. M. JONES AND J. N. CASHMAN

Dtpartmtnt ofAnaesthetics, Guy's Hospital Mtdical School (Tht Unittd Mtdical Schools), London Cardiac arrhythmia* occur commonly during general nr|q'*fttril"fifl for Hfntal extractions. There is a higher inri^^ryf when using halothane as opposed to enflurane—the mechanism suggested being increased sensitivity of the myocardium to <-flt<-r-hr>lflminiT when halothane is used (Wright, 1980). It has been demonstrated that isofhiranc is associated with less myocardial sensitization to catecholamines than halothane (Johnston, Eger and Wilson, 1976). We studied the incidence of rhythm disturbance during dental extractions performed under general anaesthesia using halothane or Uoflurane. Thirty ASA I patients having dental extractions as outpatients were allocated randomly to two groups to receive either halothane or isoflurane. All patients received a sleep dose of thiopentone

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Studies in man (Polacheck et al., 1980) have suggested that lung volume change influences the duration of inspiration during enflurane anaesthesia. This effect was not confirmed in a recent study (Drummond, 1984) and the present study was designed to accentuate this possible effect in nine anaesthetized patients, by increasing lung volume with positive end-expiratory pressure. Nine patients, ASA I or II (age 42±12yr, weight 72±12kg (mean±SD)) were studied before surgery during anaesthesia with an inspired mixture of 2% enflurane and 67% nitrous oxide in oxygen. Respiratory flow and airway pressure were measured during spontaneous ventilation before and during the application of positive expiratory pressures ranging from 0.09 to O.S4kPa. Airway occlusion was applied separately during inspiration and during expiration. Airway pleasure and hrnr-f respiratory riming were measured. Using measurement of tidal volume and the airway pressure generated by occlusion of expiration, the increment of lung volume caused by the application of PEEP was calculated. The duration of inspiration was not significantly changed by airway occlusion neither before nor during the application of PEEP (fig. 2). This suggests that lung volume does not reflexry influence inspiratory duration in man during enflurane and nitrous oxide a.ntt^tn
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BRITISH JOURNAL OF ANAESTHESIA

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TABLE II. Details of patients studied Halothane

Isoflurane

5 10 27.87 (8.98) 18-53 63.97 (13.42) 48-99 19.27 (11.38) 7-44

8 7 25.67 (6.55) 19-44 65.33 (11.80) 44-88 21.40 (10.38) 8-45

Nodal rhythm Ventricular ectopics Supraventricular ectopics

1 5 0

0 0 1

(No arrhythmia*)

9

14

Male Female Age(yr) range Weight (kg) range Time(min) range

Our results are in agreement with previous observations that halothane is associated with a high incidence of ventricular arrhythmias during dental anaesthesia (Ryder, 1970). In this study no patient was noted to have a ventricular arrhythmia during isoflurane anaesthesia and only one patient was noted to have supraventricular ectopic beats. The lower incidence of arrhythmia* associated with isoflurane was statistically significant (P < 0.05). However, the mean heart rates of the patients in the isoflurane group (range 85.26-119.11 beatmin"1) were significantly higher (P<0.001) when compared with the halothane group (range 66.31-97.5 beatmin"1). REFERENCES

Johnston, R. R., Egcr, E. I., and Wilson, C. (1976). Anesth. Analg., 55, 709. Ryder, W. (1970). Anaesthesia, 25,46. Wright, C. J. (1980). Anaesthesia, 35, 775.

THE DIFFERENTIAL NERVE BLOCKING ACTIVITY OF A SERIES OF AMINO-ESTER LOCAL ANAESTHETIC DRUGS J. A . W . WlLDSMTTH, A . J. GlSSEN*, J . GREGUS* AND B . G COVTNO*

Department of Anaesthesia, Harvard Medical School, Brigham and Women's Hospital, Boston, Ma., U.S.A. The nerve axons of peripheral nerve fibres are classified according to their speeds of conduction as types A, B or C. Recent work, concentrating on amide local anaesthetics, has challenged the traditional view that A fibres are less sensitive to blockade by local anaesthetics than C fibres (Gissen, Covino and Gregus, 1980). Since most of the early clinical and laboratory work on which that view was based utilized ester drugs, the present study was designed to examine the in vitro differential nerve blocking activity of a series of ester drugs. Cervical vagus nerves from albino rabbits were desheathed and mounted in an airtight chamber that permitted electrical stimulation (at 0.0167 Hz) of the nerve and recording of compound action potentials (for A, B and C fibres) via storage oscilloscopes. The miHrfli- section of the nerve was perfused with drug solution until rhangr* in all three compound action potentials were stable. Subsequent recovery to 90% of control was required for a valid experiment. All experiments were at room temperature. Submaximally blocking concentrations of procaine, chloroprocaine, amethocaine, procainamide and dimethyl amino ethyl para-amino benzoic acid ester (Di-MAP) were used to construct dose-response curves for the effect of each drug on the three fibre types. Effect was measured in terms of the percent decrease in the amplitude of the compound action potential (at the time of stable block) and was plotted on a probit scale against log drug concentration to allow derivation of the ED JO (Miller and Tainter, 1944). T .ini-nr plots of the decreases in the amplitudes of the compound action potentials with time (rate of block) were made for A and C fibres. The ED JO for the effect of each drug on each fibre type is shown in table m . TABLE HI. ED& for the effect of each drug on each fibre type EDJO (mmol)

Drug Amethocaine Chloroprocaine Procaine Di-MAP Procainamide

A 0.007 0.17 0.41 1.68 2.90

B 0.008 0.20 0.47 1.83 3.22

C 0.014 0.23 0.71 2.87 5.00

The rate of development of C fibre blockade was of the same order with equipment concentrations of each drug. With the drug of greatest potency, amethocaine, A fibre blockade developed before C fibre, whereas it developed considerably more slowly than C fibre with procainamide, the drug of lowest potency. Relating these results to previous studies indicates that the traditional views on differential axon sensitivity may have arisen because of confusion of absolute axon sensitivity with rate of development of blockade.

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followed by suxamethonium 1 mgkg"1 to facilitate nasotracheal intubation. Anaesthesia was maintain**! using 67% nitrous oxide in oxygen with halothane or isoflurane added using a recently calibrated vaporizer (Fluotec Mk 4 or Fortec, Cyprane Ltd). The concentration of the selected agent was adjusted to provide suitable operating conditions. A Bain type co-axial breathing system was used, delivering a fresh gas flow sufficient to minimize rebrrathing during spontaneous respiration. End-tidal carbon dioxide was displayed continuously and recorded using an infrared analyser. An ECG (standard lead H) was displayed continuously and a hard copy made of any rhythm disturbance. Arterial pressure and heart rate were measured at 60-8 intervals using a Dinamap. Table II documents age, weight and sex distributions, operating times and the incidence of arrhythmias in the two groups. Data are expressed as mean (SD), and statistical analysis utilized Fisher's exact and Student's f test as appropriate.

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY REFERENCES

Gisien, A. J., Covino, B. G., and Gregus, J. (1980). Anesthesiology, 53,467. Miller, L. C , and Tainter, M. 1_ (1944). Proc. Soc. Exp. Bid.

THE CEREBRAL FUNCTION ANALYSING MONITOR: AN ASSESSMENT OF THE EFFECTS OF HALOTHANE K. J. WARK*. P. S. SEBEL AND C. VERGHESE*

Anaettherics Unit Dtpanmenx of Clinical Nturopkysiology S. J. W. EVANS*

Dtpartmtnx of Epidemiology, The London Hospital Medical Cotltgt, Whitechaptl, London. Previous studies with the Cerebral Function Analysing Monitor (CFAM) showed that anaesthesia with nitrous oxide in oxygen and halothane produced a progressive decrease in processed EEG amplitude and a shift to lower frequencies (Sebel et al., 1984). When nitrous oxide was used alone, a significant decrease in EEG amplitude with increasing concentrations of nitrous oxide was observed without any major alterations in EEG frequency (Williams et al., 1984). The purpose of this study was to assess the effects of increasing concentrations of halothane, used alone, on the CFAM recording. Following ethics committee approval, eight unpremedkated patients (ASA I) (six female) mean age 36.3 ± 4.00 yr were studied. Anaesthesia was induced with halothane in oxygen and continued, following suxamethonium and cndotracheal intubation, using intermittent positive pressure ventilation. Anaesthesia consisted of 15mineachof 1MAC and 2MAC (0.75% and 1.5%) end-tidal halothane in oxygen measured using an Engstrom EMMA. Arterial pressure, heart rate and respiratory rate were monitored regularly. End-tidal carbon dioxide (measured with a Gould Godart Mk III capnograph) was maintained between 4 and 5%. A continuous CFAM recording was made and transmitted to magnetic tape for off-line analysis. Data are presented as mean ± SEM and statistical analysis was with one-way repeated measures analysis of variance (BMDP2V). The CFAM was recorded for 5min before induction and continuously recorded throughout ISmin each at 1MAC and 2MAC. Data were analysed from the digital tape pre-induction and first and last 5-min of each of 1 MAC and 2MAC halothane.

The mean amplitude rhangi-H significantly over time, increasing at 1MAC and decreasing at 2MAC, but did not return to the pre-induction value. The frequency data were analysed using the ratio of the log delta to beta bands and this ratio showed an increase of delta activity with respect to beta activity with increasing concentrations of hnlnrhnnr (table IV). The Cerebral Function Monitor was limited in that it provided no information on the frequency content of the EEG. The CFAM provides H^T^ilr^ frequency analysis using a modified zero crossing technique. Halothane alone produces predominantly an EEG shift to lower frequency activity with no decrease in overall amplitude. Of the changes seen in our original study (Sebel etal., 1983), the amplitude changes are mainly an effect of nitrous oxide and the frequency shift appears to be attributable to halothane. REFERENCES

Sebel, P. S., Maynard, D. E., Major, E., and Frank, M. (1983). Br. J.Anattth., SS, 1265. Williams, D. J. M., Morgan, R. J. M., Sebel, P. S., and Maynard, D. E. (1984). Anaesthesia, 39, 422.

COMPARING EXTRADURAL AND I.V. DIAMORPHINE AND BUPRENORPHINE AFTER ABDOMINAL SURGERY J. ALEXANDER AND A. M.

S. BLACK

Sir Humphry Davy Department ofAnarnhrnn, University ofBristol

In this continuing study, 47 patients have been studied in four randomly allocated treatment groups: extradural diamorphinc (ED), i. v. diamorphinc (ID), extradural buprenorphine (EB)and i.v. buprenorphine (IB). After premedkation with temazepam, they all received thiopentone, halothane or fentanyl, alcuronium and nitrous oxide in oxygen. In all patients, an extradural catheter was inserted between T5 and T10, depending on the expected incision. Extradural bupivacaine, 0.5% plain, was the principal intraoperative analgesic, supplemented when necessary by halothane and occasional small doses of fentanyl. The ED and ID groups received a loading dose of diamorphine 3 mg at the start of the procedure and an infusion of 20 mg in 0.9% saline 10 ml over the 48 h from their recovery from anaesthesia. The EB and IB groups received a loading dose of buprenorphine 0.15mg, followed by a 48-h infusion containing 0.9 mg. In the ED and EB groups, the test opioids were given extradurally; in the ID and IB groups, they were given i.v. For postoperative analgesia, i.m. injections of pethidine 50 mg were offered 2-houriy and before physiotherapy, to supplement the test regimen, the numbers of such supplements being taken as TABLE IV. Amplitude and log ratios ofthe CFAM ncording(± SEM) the main index of Arfirirnrir* in the regimen. When questioned on the first and second roomings after operation, most patients were satisfied with their analgesia, irrespective of the number of Mean pethidine supplements. The patients were managed on three Log Delta Beta amplitude general surgical wards where extradural opkjid infusions were already well accepted. Respiratory rate was counted every 10 min for the first 2h, hourly for 24h, and 2 hourly thereafter. The 58.9±3.89 Pre-inductiom -0.517 ±0.200 infusion was stopped if the rate decreased to less than 10 b.p.m. 69.4±3.39 First 5 mini MAC 0.067 ±0.295 When this happened, it did so very gradually. Eight patients 71.2±3.13 Last 5 mini MAC 0.028 ±0.284 complained of di//innw or light-headedness. This was seen more 64.0±3.23 First 5 rain 2MAC 0.346±0.308 in preliminary trials with higher doses of buprenorphine, and 63.6±3.11 Last5min2MAC 0.500 ±0.245 limited its dose rate in the study.

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D. E. MAYNARD*

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1284P TABLE V.

Results Treatment group

ID

Efi

IB

12 58 12.9

11 55 12.1

11 51 13.6

13 49 13.3

1.9 1.6 1 1

5.9 3.0 0 1

5.1 4.3 1 1

5.5 3.7 0 5

The resultB «iip""°" T H in table V indicate that the effectiveness of extradural and i. v. infusions may be Hi«ringiri«hahli- in the case of diamorphine, but not with buprenorphine. Differences in the requirements for pethidine supplements between and within the diamorphine groups were not obviously related to differences in morphine concentrations in blood samples taken on the first 2 day* after operation. ACKNOWLEDGEMENT

Graseby Medical Ltd, Watford, gave help with assay cost*.

THE EFFECT OF ADDED POTASSIUM ON AXILLARY NERVE BLOCK WITH PRILOCAINE OR BUPIVACAINE M. R. PAHJUS* AND W. A. CHAMBERS

Department ofAnaesthesiaj Princta Margartt Rose Orthopatdic Hospital, Edinburgh The axillary approach to the brachial plexus is a block which is technically easy to perform. It is used widely in our practice for elective forearm and hand surgery, either solely, with sedation, or combined with a general anaesthetic. It provides good intraoperative and postoperative analgesia; however, the time for the block to become fully effective is often around 30 min. Kircha, Barsa and Fink (1983) have demonstrated potentiatkm of the effects of lignocaine in a rat infraorbital nerve block preparation with the addition of physiological adjuvants; however, no difference was found with the addition of potassium to solutions of prilocaine for i.v. regional anaesthesia (McKeown and Scott, 1984). We wished to determine whether the addition of physiological concentrations of potassium to solutions of prilocaine or bupivacaine had any effect on the pattern of sensory and motor loss following axillary brachial plexus block. Twenty patients received 1% prilocaine 40 ml and 20 received 0.25% bupivacaine 40 ml. In each group of 20, 10 patients were randomly allocated to receive potassium chloride 0.2mmol, which was added to the solution of local anaesthetic immediately before injection. All assessments were carried out "doubleblind". The onset and spread of sensory and motor block were a slutted every 5 min for 30 min after injection, before the start of surgery. In the patients who received prilocaine no «ignifi<-ant differences in the pattern of sensory or motor loss were produced by the addition of potassium. In those who received bupivacaine, however, there was a tignifirnnt inxreate in the speed of onset of sensory loss.

REFERENCES

Bromage, P. R., and Burfoot, M. F. (1966). Br. J. Anaesth., 38, 857. Kircha, S., B a m , J., and Fink, B. R. (1983). Br.J. Anaatk., 55, 549. McKeown, D. W., and Scott, D. B. (1984). Br. J. Anaath.,(jn press).

A DATA ACQUISITION SYSTEM FOR EXPERIMENTAL ANAESTHETICS M. A. STAFFOBD, J. BROOKER* AND C. J. HULL

DepartmentofAnaesthesia, University ofNewcastle upon Tyne The standard method of investigating the Hiniral properties of short-acting anaesthetic agents or adjuvants is a randomized rlinirai evaluation of the effect of the agent during anaesthesia for a standard operative procedure. We present an improved method of collecting and handling the information generated by such a trial, which also decreases observer error and observer bias. This computer-based system appears similar to the anaesthetic record systems previously presented (Cushman and Bushman, 1983). However, emphasis is placed upon protocol conformity, with accuracy and completeness of the experimental data, and no attempt is made to maintain a full Hiniral record. The central computer (Hewlett-Packard 87) and its peripherals are mounted on a wheeled trolley which stands near the anaesthetic machine. Arterial pressure and heart rate data are acquired from a Dinamap 845 connected to the central system. AMagtrak turbine rcspirometer is also connected to the central system to measure respiration. When switched on, the computer reads the details of the procedure from a disc file. Patient identification is then entered from the keyboard. Once satisfactory recording of respiration is established, a set of control readings is taken and the triallist is prompted to start the induction sequence. The time (to 1 ms) and type of each event is recorded by the operator pressing an appropriate key on the computer keyboard. Entries are confirmed and prompts issued by audible tones of varying pitch. Less urgent messages appear on the Visual Display screen, together with a display of the current status of patient and experiment. The complete record is stored on a floppy disc and includes: (a) Mean arterial pressure and heart rate taken every minute. (b) The time and volume of each expiration and the time of the following events: (c) administration of any drugs in the protocol; (d) main features of the operation; (e) start and end of main side-effects such as evoked movement; (f) two indices of recovery. The collected information is analysed off-line, using the same computer type. Drug doses, minute volumes and die rime and length of any apnoeic periods are ralmian-H Results are presented in various ways. First, a narrative form is printed to

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No. of patients Ageyr (SD) No. of pethidine supplements (SD) Infusions stopped Dizziness

ED

Other workers have tried the effects of higher concentrations of potassium (Bromage and Burfoot, 1966), but side effects precluded further investigation. We feel that the addition of physiological concentrations of potassium to local anaesthetic solutions in order to increase the speed of onset of the block deserves further study.

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY become a permanent record. Data from the whole trial population are analysed by standard statistical programs, and in one study the whole database has been transferred to another centre for analysis as part of a multi-centre trial.

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(Jones and Prys-Roberts, 1983). During recovery from methohexitone anaesthesia, rapid and repeated resetting of the baroreflex occurred, consistent with observations made during natural sleep (Smyth, Sleight and Pickering, 1969).

REFERENCE

REFERENCES

Cushman, J., and Bushman, J. A. (1983). Br. J. Anaath., 55, 24OP.

Bristow, J. D., Prys-Roberts, C , Fisher, A., Sleight, P., and Pickering, T. G. (1969). Antstktsiology, 31,422. Jones, D. F., and Prys-Roberts, C. (1983). Br. J. Anaath., 55, 849. Smyth, H., Sleight, P., and Pickering, G. W. (1969). Cm. Rts., 24,109.

J. A. CAJCTEE*, T. N. S. CLARKE AND C. PRYS-ROBERTS

Sir Humphry Davy Dtpartmtnt ofAnaathaia, Univtrsity ofBrutol Although the effects of barbiturates and other anaesthetics in decreasing the sensitivity of the baroreflex control of heart rate have been reported widely, no information has been available on the return of the baroreflex to normal during recovery from anaesthesia. We have studied the recovery of the baroreflex following methohexitone-nitrous oxide anaesthesia in 11 healthy patients aged between 25 and 45 yr undergoing body surface surgical procedures. The patients were premedicated with morphine 0.15mgkg~' 1 h before the study. Anaesthesia was induced with methohexitone 1.5mgkg~' and mnintairwH for 30min before surgery with an infusion of methohexitone at 60 fig kg' 1 min~v to supplement 67% nitrous oxide and oxygen breathed spontaneously from a Magjll system. During surgery the infusion rate of methohexitone was increased to, and mninrairwH at 120ngkg" ! min"1. Baroreflex activity was tm^nn^i by measuring the heart rate response to a phenylephrine (l-2ngkg~')-induced increase (25-30mmHg) in arterial pressure (Bristow etal., 1969). Such assessments were made before induction of anaesthesia, after 30-min infusion of methohexitone at 60 \i% kg"1 min'^attheend of anaesthesia and surgery at a methohexitone infusion rate of 120ngkg-' min-',andat2 ) 5,10,15,30,60,90and 120minafter the *™\ of anaesthesia. During maintenance methohexitone infusion patients showed a decrease (P<0.01) of baroreflex sensitivity (ms increase of RR interval per mmHg increase of systolic arterial pressure) of > 50% of the awake baseline values. Following termination of anaesthesia, seven of the 11 patients showed a gradual increase of baroreflex sensitivity with a return to their awake baseline values at 60 min. The other four patients showed a rapid return of baroreflex sensitivity to awake baseline values within 5 min of stopping the methohexitone infusion. The four patients who showed rapid return of baroreflex sensitivity were distinguished by their much higher baseline baroreflex sensitivities (20.3±1.4SEMms mmHg"1) than those of the other seven patients (7.3 ± 1.2 SEM ms mm Hg"1). All patients showed resetting of the baroreflex during anaesthesia. In eight patients the resetting resulted in higher heart rates for a given systolic arterial pressure, as previously demonstrated for patients shortly after induction with thiopentone or Althesin (Bristow et al., 1969; Jones and Prys-Roberts, 1983), whereas the other three patients showed resetting in the opposite direction as found during maintenance infusion anaesthesia with Althesin

REVERSAL OF BLOCK FROM ATRACURIUM WITH EDROPHONIUM IN ANEPHRIC PATIENTS J. M. HUNTER, C. F. BELL AND R. S. JONES

University Dtpartmtnt ofAnatttkaia, Royal Uvrrpool Hospital Neostigmine adequately re verses residual neuromuscular blockade after atracurium and has been administered to anephric patients (Hunter, Jones and Utting, 1982a). However, neostigmine, itself can cause a depolarizing block (Payne, Hughes and Al Azawi, 1980) and it was thought that the shorter acting edrophonium might be a more appropriate agent when atracurium, which is itself short acting, had been used. Initially, edrophonium 1 ing kg"1 was administered to two patients who had considerable residual blockade, the ratio of first twitch to control (A'/A) being less than 10%. Reversal was unsatisfactory, despite additional edrophonium (0.5 mgkg"1). In addition, one patient had diplopia after operation. After this initial experience edrophonium 1 mgkg"1 was administered to 10 anephric patients when the mean ratio A'/A was 25%. The results were compared with those from 21 patients given neostigmine in one or two doses of 2.5 mg according to a previously published procedure (Hunter, Jones and Utting, 1982b); 16 received the smaller dose and five the larger. The first dose was given when the mean value of A'/A was nimiiar to that in the edrophonium group (28%). In all patients atropine was given before the anticholinesterase. Recovery was more rapid with edrophonium. Thus, both the ratios A'/A and D'/A' (fourth twitch of the train-of-four to the first) were greater for each of the first 5 min after the edrophonium had been given. In addition, at the end of the study period (at least 7 min after the reversal agent had been given) recovery was more complete in the edrophonium group. However, though the rate of reversal was faster with edrophonium there was evidence that it was less well sustained. Thus two of the 10 patients who received this agent complained of diplopia in the period after operation, despite the fact that the initial recovery had been apparently satisfactory. No such complaints were found in the neostigmine group. It would seem that edrophonium is not a suitable agent for reversing neuromuscular blockade in anephric patients, even when atracurium has been administered and spontaneous recovery has reached the stage when A'/A is 25%. ACKNOWLEDGEMENT

This work was financed in part by Roche Products Limited.

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RECOVERY OF BAROREFLEX CONTROL OF HEART RATE AFTER METHOHEXITONE-NITROUS OXIDE ANAESTHESIA IN MAN

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REFERENCES

Hunter, J. M., Jones, R. S., and Utting, J. E. (1982a). Br. J. Anatsth.,54,1251. (1982b). Br. J. Anatsth., 54,1243. Payne, J. P., Hughes, R., and Al Azawi, S. (1980). Br. J. Anaath., 52,69.

Hammond, J., Wright, D. J., and Walmsley, A. (1983). Br. J. Anatsth., 55, 248P. Lehane, J. R., Jordan, C , and Jonei, J. G. (1979). Br. J. Anatsth., 51, 65P. Eiser.N. M.,Mills, J.,Snashall,P. D.,andGuz, A. (1981). dm. Sci., 60, 363.

EFFECT OF INTRAVENOUS RANITIDINE ON BRONCHOMOTOR TONE B. J. M C L E O D * , J. E. HAMMOND AND D. J. WRIGHT*

Both Hi- and H^receptors are known to exist in the lung. The role of the H preceptor and its antagonists is well established, but there has been much debate over the role of H2-receptors in man (Eiseretal., 1981). A previous study by Hammond, Wright and Walmsley (1983) in intubated post-cardiac surgery patients showed that cimetidine caused predominantly bronchodilatation. Whether this was a result of H2-blockade or partial Hi-blockade was unknown. Ranitidine is a pure ^-antagonist, and since it is now aHmini«tered routinely to our cardiac patients after surgery, we were able to study its effect on specific airways conductance (sG. „ ) using the forced oscillation technique developed at Northwick Park (Lehane, Jordan and Jones, 1979). Fifteen patients without a history of respiratory disease were studied. Once the patients were stabilized in the intensive care unit, five baseline measurements were made of sG. „ over ISmin. Eleven patients then received ranitidine 50 mg i.v. as a bolus and four received no drug, acting as controls. A further 10 measurements were then taken over 30 min in all patients. Values of sG. „ were logarithmically converted as sG. „ follows a log normal distribution. Mean conductance was compared before and after administration of the drug, using Student's rtest. Eight patients showed a statistically significant increase ( i ' < 0 . 0 5 ) in sG. „ , one patient showed a decrease, and two did not change. The mean values of s G . n for all 11 patients who received ranitidine showed a statistically significant increase (P < 0.05) using the paired rtest. No changes were detected in the control group.

FIG. 3. Changes in specific airways conductance (sG. n ) following ranitidine SOmgi.v. This study shows that ranitidine causes significant bronchodilatation in this group of patients and supports the view that H^receptors mediate bronchoconstriction in man.

R. L. DOYLE*, P. Fofix, W. A. RYDER* AND L. A. JONES*

Nuffuld Dtpartmmt of Anatsthtrics, University of Oxford, Oxford Despite extensive investigations of the actions of potent inhalation agents on myocardial performance, little has been published concerning the modification of diastolic events by these agents. For enflurane, the time constant of left ventricular isovolumic pressure decline increased when the concentration was increased from 0.5 to 1.5 MAC (Cutfield et al., 1982). Impaired or incomplete relaxation can increase early diastolic myocardial wall tension and cause increased resistance to ventricular filling. This study was undertaken to test the hypothesis that halothane also increases the time constant of isovolumic relaxation, and that the prolonged isovolumic relaxation is associated with a decrease in coronary blood flow. Experiments were conducted in seven dogs in which global haemodynamic responses and left anterior descending coronary blood flow were measured as halothane anaesthesia was deepened. With normocarbic controlled ventilation, four levels of inspired halothane concentration (0.7,1.2,1.7and2.2%)were studied. Sonomicrometry was used to ascertain that normal contractile function was present throughout the dose-response studies. The time constant of relaxation was calculated from high fidelity recordings of left ventricular pressure (LVP) analysed at 4-ms intervals from the time of aortic valve opening to the time (before mitral valve opening) when LVP reached a value lOmmHg greater than left ventricular end-diastolic pressure. During this period, LVP declines exponentially and the time constant of pressure decrease (T^tn) can be calculated (Frcdericksen, Weiss and Weisfeldt, 1978). Phasic coronary blood flow was recorded and volume flow was measured by planimetry. Total, diastolic and isovolumic coronary flow were calculated. Increasing the inspired halothane concentration from 0.7 to 2.2% caused significant dose-dependent depression of mean arterial pressure, LV APIitmMX, aortic blood acceleration, cardiac output, coronary perfusion pressure and coronary blood flow. T^ta increased from 29(±SEM 1.3)ms to 42.5(±SEM 1.9)ms ( P < 0 . 0 5 ) . Systolic coronary blood flow and diastolic coronary blood flow as a percent of total flow remained essentially unchanged, representing between 22 and 27, and 73 and 79% respectively. Coronary flow during isovolumic relaxation, however, decreased significantly from 8.4(SEM± 1.3)% to 3.4(SEM±0.8)% ( P < 0 . 0 5 ) of diastolic coronary flow as the halothane concentration increased from 0.7 to 2.2%. This study demonstrated that halothane prolongs isovolumic relaxation; this is accompanied by a decrease in the isovolumic component of coronary blood flow without an overall disruption of the time-related distribution of coronary flow between diastole and systole.

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Dtpartmmt of Anaesthesia, King't CclUge Hospital, London

EFFECT OF HALOTHANE ON LEFT VENTRICULAR RELAXATION

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY REFERENCES

Cutfidd, G. R., Francis, C. M., Foex, P., Ryder, W. A., and Jones, L. A. (1982). Br. J. Anaesth., 54,1140. Fredericksen, J. W., Weiss, J. L., and Weisfeldt, M. L. (1978). Am. J. PkysioL, 235, H701.

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anaesthexia (Dole, Montville and Bishop, 1981). These results confirm the coronary vasodilating action of isoflurane. Furthermore, they suggest that at the doses of isoflurane studied, the capacity for vasodilatation in response to oxygen lack is reduced, but autoregulation is not abolished. The diminution in coronary vascular reserve was directly related to declining coronary perfusion pressure. REFERENCES

ISOFLURANE ANAESTHESIA AND CORONARY VASCULAR RESERVE

Nuffield Department ofAnaesthetics, University of Oxford It is accepted generally that isoflurane anaesthesia induces coronary vasodilatation (Tamow et al., 1977). Such vasodilatation might prejudice the ability of the coronary vasculature to increase flow in response to sudden increases in myocardial oxygen demand, that is coronary vascular reserve (Klocke et al., 1976) may be diminished by isofhirane anaesthesia. To assess the effect of isoflurane on coronary vascular reserve, experiments were conducted in seven dogs in which overall haemodynamic responses and left anterior descending (LAD) coronary artery blood flow were measured as isoflurane anaesthesia was deepened. With normocarbic controlled ventilation and at 51evelsof alveolar isoflurane (mean values 0.57,0.85,1.13, 1.41 and 1.70%) the effecti of a 10-s occlusion of the LAD artery were recorded. Sonomicrometry was used to ascertain that normal contractile function had been restored in the segment of myocardium supplied by the temporarily occluded artery before proceeding to the next dose.

(1976). Prog. Cardiol.,

5,1.

Tarnow, J., Eberlein, H. J., Osier, G.,Patschke, D., Schneider, E., Schweickel, E., and Wilde, J. (1977). Anaesthesist,26,220.

A COMPARISON OF THE RAT AND GUTNEAPIG PHRENIC NERVE-DIAPHRAGM PREPARATIONS AS MODELS TO INVESTIGATE NEUROMUSCULAR BLOCKING DRUGS E. G. BRADSHAW, N. S. HAKFBK AND B. S. PLEUVRY

Anaesthesia and Pharmacology Departments, University of Manchester

The rat and guineapig phrenic nerve—diaphragm preparations have been used to study neuromuscular blocking agent*. The rat is generally preferred because it is more robust and a cheaper preparation. In the present study the potencies of three neuromuscular blocking agents, atracurium, tubocurarine and suxamethonium, have been compared on the two preparations. Both phrenic nervc-hemidiaphragms were dissected from TABLE VI. Selected data from extremes (0.57% and 1.70% alveolar male rats and guineapigs. The preparations were mounted in an isoflurane) of dose-response studies. Mean data for seven dogs organ bath remaining 75 ml of Krebs solution at 37 "C bubbled (±SEM). *P <0.05, **P <0.01, ***P <0.001 (paired two- with 5% carbon dioxide in oxygen. A pre-load of 4 g was applied tailed Student's t tests) to the central tendon. Supramaximal square wave stimuli of Alveolar isoflurane: 0.57%

1.70% TABLE VII. EC so and molar potency ratios relative to tubocurarine

CPP(mmHg) LAD flow (ml min"1) CVR (units) Volume debt (ml) Volume repayment (ml)

83 (5) 43 (4) 2.00 (0.82) 2.8 (0.8) 10.8 (2.3)

49 (3)*** 49 (5)n.s. 1.06 (0.16)** 3.0 (0.5)n.s. 1.8 (0.7)*

Selected data from the extremes of these dose-response studies are presented in table VI. Over the dose range examined (and measured before LAD occlusion) there was a 41% reduction in coronary perfusion pressure (CPP). Mean LAD flow increased slightly, so that effective coronary vascular resistance (CVR) declined in a dose-related fashion by 51 ± 4%. Occlusion of the LAD artery for precisely 10 s produced a "volume debt" equivalent to the product of flow and duration. "Volume repayment", calculated by planimetry of the area of the hyperaemic response above pre-occtusion mean flow, was found to decline as anaesthesia was deepened. The ratio of repayment to debt decreased from 4.6± 1.0 at0.56%to0.8±0.1 at 1.70% alveolar isoflurane. The relationship of repayment/debt ratio to coronary perfusion pressure was highly linear ( r - 1.00) and exactly similar to previously reported relationships under steady state a-chloralose

Guineapig

Rat

Man

ECJO

EC» xlO-'M

x 10'6M

±SEM

MPR

±SEM

MPR

MPR

Atracurium

15.5 (+0.80, -0.76)

10.3

0.75 (+0.10, -0.08)

0.39

0.33

Tubocurarine

1.5 (+0.80, -0.18)

1.88 (+0.14, -0.13)

1

1

10.1 (+2.3, -1.8)

5.37

2.04

15.1 Suxamethonium (+0.33, -0.32)

10.06

B=9

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G. R. CUTFIKLD, C. M. FRANCIS, P. Fofix, W. A. RYDER* AND L. A. JONES*

Dole, W. P., MontvOk, W. J., and Bishop, V. S. (1981). Am. J. Physiol., 240, H709. Klocke, F. J., Mates, R. E., Copley, D. P., and Orlick, A. E.

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benzodiazepine concentrations by gas-liquid chromatography. There was a larger peak-to-trough variation seen with the first dose in the midazolam group(239-37 ng ml"1) as compared with the diazepam group (190-66 ng ml" 1 ). Trough plasma concentrations of midazolam were stable within 6h, whereas diazepam concentrations increased steadily (table VOX). TABLE VHI. Mean (±SEM) trough plasma concentrations of bentodiazepine (ngml''). ND = None detected Time from first dose (h) Drug

8

10

Midazolam

ND

37± 6.5

46± 8.6

62± 62± 63± 11.2 10.0 11.5

Diazepam

ND

66± 12.8

75± 7.5

98± 10.1

12 64± 4.6

130± 127± 149± 17.1 8.5 15.9

Following discontinuation, plasma midazolam concentrations decreased rapidly and were tub-therapeutic within 6 h, whereas plasma diazepam concentrations remained increased 24 h later. On this basis, recovery will be much quicker after midazolam and this agrees with our clinical finHingn REFERENCE

MIDAZOLAM V. DIAZEPAM FOR SEDATION IN A CARDIAC SURGICAL INTENSIVE CARE UNIT

Harper, K. W., Lowry, K. G., Elliott, P., Collier, P. S., HaUiday, N. J., and Dundee, J. W. (1984). Br. J. Anaesth., 56, - (in press).

K. G. LOWRY, S. M. LYONS, I. W. CARSON, I. A. ORR AND J. W. DUNDEE

Department of Anaesthetics, The Queen's University of Belfast and Department of Clinical Anaesthesia, Royal Victoria Hospital, Belfast It is common practice to institute a short (6-18h) period of controlled ventilation following open heart surgery. In order to facilitate this, a sedative regimen, usually including a benzodiazepine, is prescribed. Until recently, diazepam has been the agent of choice. However, it has a long elimination half-life and its main metabolite is also hypnotically active: these combine to produce prolonged recovery unless dosage is kept to a minimum. The recently introduced water soluble imidazo-benzodiazepine miHmnlanij with a short half-life, would appear to offer an alternative to diazepam for repeat usage. The elimination half-life of midazolam varies from 2 to 3 h in healthy volunteers and young adults undergoing minor surgical procedures. However, following cardiopulmonary bypass (Harper et al., 1984) it may be prolonged to about 7 h; even this is much shorter than diazepam (20-3Oh). To study the cumulative effect of diazepam or midazolam, 19 patients, following open heart surgery, were randomly allocated to receive Smg of either drug i.v. every 2 h as postoperative sedation. They had received no benzodiazepine for at least 2 weeks before operation and none was administered during anaesthesia. Supplementary i.v. doses of morphine 2 mg were oHminintered as required in both groups. Blood was drawn from each patient before the administration of the benzodiazepine and at 7.5, IS, 30,60,90and 120 min after the font dose, then every 2 h immediately before the next dose until 12 h after the first dote. After discontinuation further sample* were taken at 6, 12 and 24 h for estimation of plasma

AGE AND NATURE OF OPERATION INFLUENCE THE PHARMACOKINETICS OF MIDAZOLAM K. W. HARPER, P. S. COLUER, J. W. DUNDEE, P. ELLIOTT, N. J. HALUDAY AND K. G. LOWRY

Departments of Anaesthetics and Pharmacy, The Queen'% University ofBelfast Midazolam (MDZ) is used in high doses as an i.v. induction agent with some success. We here report the effects of age and operation on the elimination half-life and other pharmacokinetic parameters of 0.3 mg kg"1. Fit patients having minor or major operation or following coronary artery surgery were studied. Fifty years was taken as the division between young and older subjects. No patient had a benzodiazepine for 48 h before operation; all received nitrous oxide in oxygen and an opioid or a competitive neuromuscular blocking drug as required. Halothanc and enflurane were avoided. Plasma MDZ was estimated using GLC at intervals for up to 18h. Distribution half-life (Tj*) was obtained from a biexponential fit of the data from individual patients. Elimination half-life ( T / ) , clearance (CI) and volumes of distribution (V) were obtained by a non-modelling method from the terminal slope and area unHw the decay curve. Compared with minor operations, Tf was significantly longer ( P < 0.005) in patient! having major procedure! or following cardiac operations (P<0.02). Age had a fig"•*•"•*" effect ( P < 0 . 0 2 ) on Tf in patients having minor but not major operations (table DC). In young patiena, Tf was longer following

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0.5 ms duration were applied to the phrenic nerve at a frequency of 0.1 Hz. The force of contraction was measured using an isometric force transducer and displayed on a Grass 79C polygraph. Concentration-response curves were constructed for the three agents using a Latin square technique and at least three concentrations applied to the preparation. A 5-min contact time was used and a 20-min dose cycle. Separate preparations were used for each drug. Log concentration-response curves were plotted for each preparation and the log ECJO determined. For convenience these results have been expressed as EC50 (table VH). Tubocurarine was approximately equipotent on the two preparations. Suxamethonium was less potent than tubocurarine on both preparations but the guineapig was more sensitive. In contrast, atracurium was less potent than tubocurarine on the rat diaphragm and more potent than tubocurarine on the guineapig diaphragm. There was almost a 20-fold difference in the ECJO for atracurium between the two preparations. The results have also been expressed as molar potency ratios (MPR) relative to tubocurarine (table VII). In addition, the table shows the MPR for tubocurarine, atracurium and suxamethonium in man calculated from published EDJO values. It can be seen that the guineapig preparation is a much better predictor of the relative potencies of these agents in man.

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TABLE IX. MeantSEM, half-life, clearance (mgkg-'h-'), and volume of distribution (litre kg~I)foryovng (— 50yr) and older (SO + yr) patients undergoing minor or major operation, and older patients after cardiac surgery Operation

Age(yr) n

a V

18

50 + 7

18±4 19±2 2.4±0.24 4.1 ±0.59 284±28 386±44 1.2±0.12 1.6±0.22 1.1 ±0.15 1.3±0.16

-50

50 +

24

14

7

31±3 30±4 29±4 3.8±0.33 3.9±0.43 4.6±0.39 374 ±32 347 ±37 412±40 2.1 ±0.22 1.9±0.24 2.4±0.10 1.7±0.16 1.5±0.19 1.4±0.15

major as compared with minor operations. Operation had no significant effect on clearance. The influence of age on d is shown in pooled groups, averaging 402 ±29 ml kg"1 h"1 in older subjects (i><0.05). In young but not older subjects V"** and V" were both significantly greater (P<0.02) in patients having major as compared with minor operations. V1"* was greater in older patients undergoing major (P<0.02) and cardiac surgery ( P < 0.001), but not significantly so with minor operations. The elimination half-life was prolonged with increased age and the extent of operation. The prolongation of Tj' with age is probably a result of reduced clearance and increased volume of distribution in the elderly. The effect of operation appears to be the result of increase in volume of distribution.

had rejection episodes sufficiently severe and prolonged, despite treatment, to warrant renal biopsy. One of these will need a new graft in due course. The remaining two achieved satisfactory renal function, albeit delayed by a week or two. The six patients with complicated rliniral progress were older than the other six. They tended to have more pronounced decreases in fibronectin. Five of them had subnormal concentrations of a2-macroglobulin before operation, and these remained subnormal after operation. The sixth started normally, but his X2-macTOglobulin concentrations decreased until the 4th day after operation, when his graft, which had infarcted, was removed. Subsequently he had a successful transplant. Otherwise, the two patients who lost their grafts early showed marked changes in the concentrations of some of the other acute phase proteins (ai-antitrypsin and orosomucoid in one, fibronectin and caeruloplasmin, in the other). They seemed to be associated with particular untoward events in the diniral course. ACUTE PHASE PROTEIN CHANGES AFTER RENAL Further studies of acute phase proteins, with larger numbers of TRANSPLANTATION patients undergoing different types of operation, may be of some value in predicting outcome and in undemanding the response to S. G. RADFORD* AND A. M. S. BLACK Sir Humphry Davy Dtpartmtnt ofAnaesthesia, University of Bristol surgical trauma. Acute phase proteins undergo marked rhangra in concentration during periods of inflammation (Whicher, 1981), or in the 7-10 days following trauma or surgery (Aronsenetal., 1972). They are predominantly gtycoproteins and are involved in blood coagulation, Cbrinolysis and phagocytosis. They regulate protease activity and influence healing. Knowledge of the effects of different surgical procedures and variations in anaesthetic and analgesic technique on protein change is still at a descriptive stage. In a pilot study, we have monitored the concentrations of C-reactivc protein, ai-antitrypsin aj-antichymotrypsin, caeruloplasmin, orosomucoid, aj-macroglobulin and fibronectin in 12 consecutive patients who received renal allographs. Protein concentrations were measured using the rocket immunoelectrophoresis technique. In six patients, the postoperative progress was smooth, complicated by minor episodes of suspected rejection which responded promptly to a standard regimen of heparin and methyl prednisolone. In the remaining six, the postoperative period was more complicated. Two lost their grafts within 4 weeks, and a further patient lem his at four-and-a-half months. The nrnaining three

REFERENCES

Aronsen, K. F., Ekelund, G., Kindmark, C. O., and Laurell.C. B. (1972). Scand. J. din. Lab. Invest., 29 (Suppl. 124), 127. Whkher, J. T. (1981). Diagnostic Medicine, May/June, 52.

TENS, ANALGESIA AND PLASMA [MET]ENKEPHALIN A. DINGWALL*

Departments of Anaesthesia and Pharmacology, University of Manchester Transcutaneous electrical nerve stimulation (TENS) has been advocated for post-operative analgesia because of its lack of side effects (Tyler, Caldwell and Ghia, 1982). Whilst its mechanism of action can be explained by the gate theory of pain, it is possible that release of endogenous opioid peptides plays a role. Electrical stimulation has been shown to increase CSF [met]enkephalin

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7Y(min) 7V(h)

-SO

Post cardiac

Major

Minor

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content concurrent with observed analgi*m> activity (Stocking, 1980). Furthermore, the parenteral administration of synthetic analogues of [met]enkephalin have been found to be analgesic. The present study was HrmgnfH to investigate three questions: (1) Does TENS lower the nnn1gi-«ir requirements in postoperative thoracotomy patients? (2) Does TENS cause any consistent changes in plasma [mct]enkephalin content? (3) Can rhangr* in pla«ma [mftfrnlrrphalin piwlifr rh^ analgririr requirement of the patient?

REFERENCES

Clement Jones, V., Lowry, P. J., Rees, L. H.,andBesser,G. M. (1980). Nature (Loud.), 283,295. Stoelting, R. N. (1980). Antstk. Analg., 59,874. Tyler, E., Caldwell, C , and Ghia, J. (1982). Anath. Analg., 61, 449.

INTERACTIONS BETWEEN MEPTAZINOL AND NEUROMUSCULAR BLOCKING AGENTS

TABLE X. Effect of mepuaxnol on the twitch response of the rat phrenic nerve-diaphragm preparation to tubocurarine and suxamethonium. 'Significantly different from time matched control: P <0.05. tTime-matched control preparations are not mated with meptazinol LogECjoCigml"1')(mean±SEM) Tubocurarine Meptazinol concn GigmT') 0 0.25 0.5 1.0 2.0 4.0

Test prep.

Timematched controlt

-0.01 ±0.03 0.03 ±0.05 0.05* ±0.04 0.08* ±0.01 0.05* ±0.03 -0.05 ±0.03

-0.01 ±0.03 -0.05 ±0.04 -0.07 ±0.04 -0.05 ±0.03 -0.09 ±0.04 -0.10 ±0.05

rthnniiiTn

Test prep.

Timematched controlt

0.91 ±0.01 0.86 ±0.02

0.88 ±0.01 0.87 ±0.01

0.61* ±0.03

0.82 ±0.02

0.24* ±0.04

0.79 ±0.03

This study has shown that meptazinol can modify the actions of neuromuscular blocking agents in vitro. Experiments are continuing to determine whether this has any clinical significance. REFERENCE

K. STRAHAN AND B. J. PLBUVRY

Departments of Anaesthesia and Pharmacology, University of Manchester In the experimental animal the analgesic action of meptazinol has been shown to depend upon both opioid and cholinergic mechanisms (Bill et al., 1983). Since meptazinol can be used during operation, it seemed that there is a potential for interactions between the cholinergic activity of meptazinol and neuromuscu-

Bill, D. J., Hartley, J. E., Stephens, R. J., and Thompson, A. M. (1983). Br. J. Pharmacol, 79,191.

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Thoracotomy paticna with one major pathology were selected. Informed consent was obtained and 10-m] blood samples were collected before operation, immediately after operation and 24 h after operation. After the first postoperative sample all patients had TENS electrodes applied and adjusted. However, only in the test group was the stimulator switched on. Additional nnaler«ig in the form of papaveretum i.m. was available on request and analogue pain scores were obtained every 2 h. Each blood sample was centrifuged, the plasma frozen and extracted later via an ODS silica column. [Met]enkephalin was determined by radkrimmunoassay (Clement Jones etal., 1980). [Metjenkephalin content was expressed as percentage change from preoperative values and plotted as scattergrams against mean analogue pain scores over the subsequent 24 h. The mean analgesic requirement in the control group was for papaveretum 1.35±O.35mgkg~' 24h"' (n = 6). Patients receiving TENS required less papaveretum (0.75±0.17mgkg-' 24h->, (n = 9) (P<0.05). TENS had no significant effect upon plasma [metjenkephalin, as the changes observed in TENS patients were similar to those which occurred in control patients. However, control patients exhibited a significant negative correlation between the change in [met]enkephalin immediately after operation and the subsequent mean 24-h analogue pain score, that is the greater the increase in [met]enkephalin after operation the less the analogue pain score (r=-0.84,P<0.05). In patients given TENS this correlation was lost, suggesting that TENS was a more effective analgesic in patients with low post-operative [met]enkephalin.

lar blocking agents. This possibility has been investigated in vitro using the rat phrenic nerve-diaphragm preparation. Paired preparations were set up for indirect stimulation (0.1 Hz, 0.5 ms supramaximal voltage) in Krebs-Henseleit solution bubbled with 5% carbon dioxide in oxygen at 37°C. Concentration—effect relationships were obtained for either (+)tubocurarine or suxamethonium alone and in the presence of meptazirjol 0.25-4.0 ng ml"1. Preliminary ^n^i inr»»nt« indicated that, once applied, meptazinol was difficult to remove from the tissue. Thus, gradually increasing concentrations of meptazinol were used on the test preparation and its effects on tubocurarine and suxamethonium were assessed by comparison with a time-matched control which had not been exposed to meptazinol. In the control preparation the log EC30 for both tubocurarine and suxamethonium decreased slightly with time (table X). Meptazinol 0.5-2 ngml~'sjgniftrantry increased the log EC» for tubocurarine, indicative of antagonism. However, this effect was lost with higher concentrations. In contrast meptazinol caused a dose-dependent decrease in log EC50 for suxamethonium.

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY MAINTENANCE OF DRUG CONCENTRATIONS AT THE THERAPEUTIC THRESHOLD M. J. HARRISON

Dtpai Intent of Anaesthesia, Queen's Medical Centrt, Nottingham

FIG. 4. Relation between the "infusion factor" and ij and ti generated using the pharmacoldnetic model and a 1:1:0.5 ratio of doses.

second. The duration, in minutes, over which the second (ti) and third (t£) doses act is noted and the factor by which the third dose should be multiplied is read from the table or graph (fig. 4). If this is shown to be practicable clinically, then it should be possible to determine infusion rates for any individual regardless of their size or metabolic pathology from the two parameters—dose and time. ACKNOWLEDGEMENT

lam indebted to Dr F. Johnson and Professor C.J. Hull for thenhelp.

THE EFFECT OF ANAESTHETIC INDUCTION USING ETOMIDATE UPON PITUITARY-ADRENOCORTICAL FUNCTION P. M. YEOMAN*, I. W. FELLOWS*, A. J. BYRNE AND C. SELBY*

University and City Hospitals, Nottingham Intravenous infusions of etomidate used for sedation have been shown to produce a reversible suppression of the adrenocortical response to trauma (Fellows et al., 1983). Two recent studies of the effect of an induction dose of etomidate on cortisol secretion have given conflicting results (Fragen, Shanks and Moltcni, 1983; Sebel, Verghese and Makin, 1983). Furthermore, neither study reported the effect on pituitary ACTH response. Ten adult male patients who had given informed consent were studied. All were A.S.A Grade 1 or 2, and underwent uncomplicated surgery for repair of inguinal hernia starting around 9.00 am. All patients received an oral premedication of diazepam 10-20 mg and were allocated randomly to receive either thiopentone 4mgkg"' or etomidate 0.3mgkg~' for induction. Anaesthesia was maintain^ with nitrous oxide in oxygen and halothane or enflurane by face mask, supplemented with fentanyl 50-150 ug. Venous blood samples were taken from an indwelling mnnnli inserted at least 30 min before induction, two samples being taken

TABLE XI. Cortisol and ACTH concentrations afttr induction of anaesthesia with thiop€Hton* (n-=5) or ttomidau (n — 5) (median values and rangt). P <0.05 (unpairtd Wilcoxon test): * for cortisol; ** for ACTH Pre-induction Thiopentone Cortisol 405 (nmol litre" •) (250-430) ACTH (ng litre"1)

60 (40-90)

Etomidate Cortisol 480 (nmol litre" ') (300-635) ACTH (ng litre"1)

60 (20-100)

lh

2h

3h

680 (390-910)

900* (630-975)

130 (90-230)

120 (100-250)

90** (90-130)

90** (60-100)

390 (305-550)

415* (320-510)

405 (330-570)

610 (480-710)

260 (170-390)

230 (110-610)

190** (130-620)

360** (180-400)

6h

590 380 (360-1060) (260-1080)

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To infuse a drug at a rate that maintain* its concentration just above the value at which it produces its effect is a desirable aim. Biological variation makes the strict adherence to a formula, with fixed constants, for the determination of the infminn rate impractical. Arnnth^rnorifqlmanipulation of exponential functions has enabled the infusion rate of a drug to be determined from the time that data of the drug have their therapeutic effect. Initially, the factor by which the infusion rate was determined was obtained using an iterative technique using a single compartment model. A table of such values was produced. This proved unreliable. On receipt of a two-compartment simulation program (Hull, Newcastle Upon Tyne), the problem was inverted. Knowing the answer (the factor by which the infusion rate was to be determined) enabled the construction of a table «Jmi1nr to that described above. Three doses of the drug are given in the ratio of 1:1:0.5. The first dose increases the circulating concentration above the therapeutic threshold. The second dose is given at the time of recovery from the first dose, and the third on recovery from the

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ACKNOWLEDGEMENT

Financial support by Janssen Pharmaceutical for this study is gratefully acknowledged. REFERENCES

Fellows, I. W., Bastow, M. D., Byrne, A. J., and Allison, S. P. (1983). Br. Mtd. J., 287, 1835. Fragen, R. J., Shanks, C. A.,andMolteni, A. (1983). Lanctt,2, 625. Sebel, P. S., Verghese.C,andMakin.H. L. J. (1983). Lanctt,2, 625.

THE EFFECT OF INDUCTION OF ANAESTHESIA BY ETOMIDATE ON CORTTCOSTEROID SYNTHESIS IN MAN D . J. R. DUTHIE*, R. FRASER* AND W. S. NIMMO

Department ofAnaesthesia and Medical Research Council Blood Pressurt Unit, Wtsttrn Infirmary, Glasgow Suppression of cortisol production and an increased mortality was reported to accompany the use of etomidate by infusion in trauma patients (Ledingham u d Wan, 1983). In this study, the effects of i single bohu dose of etomidate or thiopentone on the synthesis of corticosteroid hormones and adrenocorticotropic hormone (ACTH) were studied for 24 h in 12 patients, who underwent minor surgery to the body surface under general nng^yhr^iw Twelve male patients, without evidence of endocrine disease, were randomly allocated to receive thiopentone 5mgkg~', or etomidate 0.3mgkg~' i.v. to induce anaesthesia, which was maintained with 1.5% halothme and 6% nitrous oxide in oxygen. Respiration was spontaneous. Anaesthesia was induced between 10.45 am. and 4.15 pm. and lasted 34 ± 16min. Blood samples were withdrawn 30min before ("control"), immediately after, and at 15 min, 1,4, and 24 h after induction of anaesthesia. At no time were the plasma concentrations of cortisol, corticosterone or ACTH significantly different between the two groups. Taking all 17. parii-ntt tngi-thcr, thi-n- m< aOTatwtirally«ignifimnt decrease in die cortisol concentration at 15min (i><0.01) and 60min ( P < 0 . 0 5 ) from induction of anaesthesia compared with the "control" cortisol concentration, but cortisol concentrations remained within the laboratory references range.

At 4 and 24 h, plasma 11-deoxycorticosteroid concentrations were significantly higher in the etomidate group than in the thiopentone group. This is consistent with etomidate's known inhibition of 11/}hydroxylase. This inhibition was partial, as it failed to reduce the plasma concentrations of the hormones, cortisol and corticosterone, and there was no discernable increase in ACTH. Thus, a bolus of etomidate 0.3 mg kg*1 used to induce anaesthesia causes no significant adrenocortical suppression. REFERENCE

Ledingham, I. M. A., and Wan, I. (1983). Lanctt, 1,1270.

THE EFFECT OF INCISIONAL INFILTRATION OF 0.5% BUPIVACAINE ON PAIN AFTER SURGERY H. OWEN* AND D. J. GALLOWAY*

Untoertity Department ofAnaesthesia, and Department of Surgery, Wtstern Infirmary, Glasgow Considerable pain may follow excision of benign breast lumps under local or general anaesthesia (Chetty et al., 1983). Repeated instillation of bupivacaine to wounds can provide postoperative analgesia (Hashemi and Middleton, 1983) but intra-incisional saline is also effective (Patd et al., 1983). Patients presenting for excision biopsy of a benign breast lump were studied using these agents double-blind. Premedication andflnflMthwiawere standardized and subjects were randomly allocated to receive either 10ml of 0.5% bupivacaine (group I) or 0.9% saline (group II) infiltrated to the wound before closure. Postoperative analgesia was provided by morphine or paracetamol given at the discretion of the nursing staff. Pain was assessed on a four-point scale (0 = no pain; 1 = mild pain; 2 = moderate pain; 3 = severe pain) at 1 and 24 h. Analgesic consumption over the first 24 h was recorded and the wounds examined approximately 1 week later. Table XH shows pain scores and analgesicrequirementsover the first 24h.

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before and eight sample* following induction over a 6-h period. Serum cortisol and plasma ACTH concentrations were measured (in-house and "Amersham" IM66 kit methods, respectively). The following morning at 9.00 am a short Synacthen test was performed. Cortisol and ACTH concentrations were within the normal range in both groups before induction, the difference between groups being non-significant ( P > 0.05) (table XI). Following induction, the m«-wimiim cortisol response in the etomidate group was significantly less than that for the thiopentone group, this difference becoming non-significant at 3 h after induction. A significant increase in ACTH in patients who received etomidate was observed. In conclusion, a single bolus dose of etomidate produced a significant reduction in the cortisol response to a standard surgical procedure in healthy male patients during the first 3 h.

TABLE XII. Pain scores and analgesic requirements. *Using a Fisher exact utt; **using a Mann- Whitney U test Pain scores lh

24 h

Morphine alone

Any analgesia

0 12 3

0 12

Group I

2

5

8600

1130

Group n

8

9

1533

363

0.018*

0.107*

0.0012**

0.0045**

Despite being given significantly more opioid analgesia, group H patients still had more pain than the local anaesthetic infiltration group. All wounds healed normally.

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY REFERENCES

Chetty, U., Nixon, S. J., Steele, R. J. C , and Forrest, A. P. M. (1983). / . R. Coll. Surg. Edn., 28,14. Hashemi, I. T., and Middleton, M. D. (1983). Ann. R. CoU. Surg.Eng.,6S,S&. Patd, J. M., Lanzafame, R. J., Williams, J. S., Mullen, B. U., and Hinshaw, J. R. (1983). Surg. Gyntcol. Obaet., 157,338.

J. BROOKES*, M. A. STAFFORD AND C. J. HULL

depression. While group B patients were the first to recover, the higher incidence of evoked movement and slower recovery from respiratory depression may be regarded as disadvantages. REFERENCE

Hull, C. J., and Jacobson, L. (1983). Br. J. Anaesth., 55,173S.

NASAL OBSTRUCTION, ALVEOLAR VENTILATION AND TRANSCUTANEOUS OXYGEN M. E. RAMADAN*, K. LINGE*, A. C. SWIFT* AND L. CAMPBELL

T.

Royal Liverpool Hospital, Liverpool

Department ofAnaesthesia, University of Newcastle upon Tynt Methohexitone has a number of undesirable side-effects when used as both induction and maintenance agent for short cases. These may be ameliorated by the use of an opioid before induction. Alfentanil, a short-acting opioid, has a pharmacokinetic profile ideally suited to short case anaesthesia. However, a previous study (Hull and Jacobson, 1983) comparing alfentanil 750 ng with fcntany1100 /ig (given as a pre-induction bolus) did not show any measurable improvement in the quality of anaesthesia as judged by the incidence of apnoea, severity of evoked movement, or rate of recovery. We therefore decided to use alfentanil 250 ng before induction and to compare three concentrations of alfentanil in methohexitone with methohexitone alone as the incremental agent. Four groups of 32 patients due to undergo short gynaecological procedures took part in a randomized, double-blind study using the computer data acquisition system described at this meeting. After a bolus of alfentanil 250ng, anarsthrsia was induced with 1% methohexitone with 0.1% lignocaine at a standard rate and ynpinrairwH by mrflmr of i.v. increments. In group A, each increment contained methohexitone 5 mg, while in groups B, C and D each increment consisted of alfentanil 15.6, 31.2,46.5 ug together with methohexitone 2.5 mg. Each patient was given 60% nitrous oxide in oxygen until the end of cervical dilatation, thereafter breathing oxygen alone. Recovery was assessed as the time from the last increment to the mean of that required for the patient to show her tongue, and then her left thumb, on command. The study showed clear differences between the groups. Alt patients developed respiratory depression, with minute volumes decreasing to approximately 40% of control values by the time skin preparation began. Minute volume in all group A patients had returned to that measured during the control period by the end of cervical dilatation. Patients in group B recovered more gradually, while patients in groups C and D showed no significant recovery at that time. Moreover, a large proportion (73%) of patients in groups C and D moved in response to surgery, with the least incidence of movement recorded in group A (30%). The most rapid recovery was exhibited by patients in group B (2.5min); significantly faster than patients in group A (4 min) or D (3.5 min). Ten per cent of patients complained of pain on injection with methohexitone. While all patient groups showed increased heart rate and decreased mean arterial pressure, there were no significant inter-group differences. It was concluded that the higher dose mixtures (groups C and D) were associated with an unacceptable degree of respiratory

It is a common observation that patients with blocked noses feel "under the weather" and often have difficulty sleeping. This discomfort improves when the obstruction is relieved. Likewise, neonates and young animaU are obligatory nose breathers and chronic obstruction in young rabbits has been shown to produce chronic hypoxaemia and hypercarbia (Ramadan, 1983). The effect of the route of breathing (nasal or oral) on pulmonary ventilation, physiological deadspace and transcutaneous oxygen tension was investigated in 42 healthy young adults aged 20-30 yr (28 men) free of disease of the respiratory tract. Mouth breathing was induced with a nose clip. Expired air was collected into a bell spirometer, using an RAF face mask. Tidal volume, minute volume and respiratory frequency were recorded by the spirometer. Mixed expired PCO2 and end-tidal PCO2 were measured using a mass spectrometer. V D / VT and total deadspace were calculated from the Bohr equation. Physiological deadspace was calculated from the total deadspace less the deadspace of the mask. Transcutaneous oxygen tension was measured on the forearm using a Radiometer TCM1 TC Oxygen Monitor. After the reading had stabilized and following the ventilation measurements, subjects breathed, first, through either the nose or mouth for 10 min and the transcutaneous oxygen tfnm'nn during the last 5 min was recorded. They then breathed via the other route for 10 min and again transcutaneous oxygen tension was recorded during the last 5 min. The order of nasal or oral breathing first was randomized for both the ventilation and the transcutaneous measurements. None of the subjects was aware of the object of the investigation. In the male subjects nose breathing was associated with a significantly hiflhw minute volume than mouth breathing (mean±SEM; nose: 1O.71O±O.55O litremin-'; mouth: 9.040±0.530 litre min"1 (P<0.01)) and a significantly higher alveolar ventilation (nose 7.910±0.3O0 litre min"1; mouth 6.670 ± 0.280 litre min"1 (J>< 0.001). This was entirely the result of a higher respiratory frequency (nose: 15.5± l.Ob.p.m.; mouth: 13.3±0.8b.p.m. (P<0.01)). There was no difference between nose and mouth breathing in tidal volume nor physiological deadspace. Nose breathing was associated with a small (0.17-kPa) but significantly higher transcutaneous oxygen tension (P<0.01). In women there was no difference in minute volume, tidal volume, alveolar ventilation, respiratory frequency, physiological deadspace or transcutaneous oxygen tension between nose and mouth breathing. The decreased alveolar ventilation and the lower transcutane-

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ANAESTHESIA FOR SHORT PROCEDURES: A COMPARISON OF DIFFERING CONCENTRATIONS OF ALFENTANIL IN METHOHEXITONE

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BRITISH JOURNAL OF ANAESTHESIA surgery ( P < 0.005). We suggest that this improvement could be the result of differences in alveolar ventilation brought about by the operation. In a similar population of 34 patients there was a significant correlation (r = 0.51, P < 0 . 0 1 ) hnin» n rnmnnitanrous oxygen tension and arterial oxygen tension. REFERENCE

Ramadan, M. F. (1983). dm. Otolaryngoi., 8,245.

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