Anaesthesia, 1992, Volume 47, pages 741-746

Vecuronium: an anthropometric comparison

I. T. HOUGHTON. C. S . T. AUN

AND

T. E. OH

Summary This study set out to determine if there was any resistance to vecuronium in Nepalese studied in Nepal compared with Nepalese, Chinese and European patients studied in Hong Kong. The four groups, each of 10 male and 10 female patients, were intubated 60 s after administration of 0.1 mg.kg-' vecuronium. The Nepalese patients in Nepal had significantly less satisfactory intubating conditions ( p = 0.002). Similarly, male patients had significantly less satisfactory conditions than female patients ( p = 0.004). Some anthropometric measurements were significantly different between the patients in Nepal and those in Hong Kong. There were also sex-related anthropometric differences. It is suggested that differences in response to vecuronium could be explained by differences in distribution volume and muscle mass

Key words Neuromuscular relaxants; vecuronium. Genetic factors; race.

Although genetic variation causing differences in drug metabolism is well recognised [I], little work has been done on the effect of race or geography on muscle relaxants, other than the incidence of cholinesterase variants [2]. However, Katz et al. noted that the durations of action and magnitude of neuromuscular blockade of suxamethonium and tubocurarine were prolonged in Americans compared with the British [3]. This transatlantic difference was also found in USAF servicemen stationed in the UK. Levy [4], in a pharmacokinetic analysis of Katz's data and also that of Walts and Dillon [S] who had investigated the interaction of tubocurarine and suxamethonium in Los Angeles, suggested that the transatlantic differences with suxamethonium could be explained by a slower elimination in the New York population compared with those in Los Angeles or the UK. On a visit to Nepal on Operation Nightingale [6] to help with earthquake relief at the British Military Hospital in Dharan (Nepal), the anthropometric differences between the Nepalese living in Nepal and the Nepalese soldiers and their families serving in Hong Kong (Ghurkas) were very obvious. It was therefore decided to extend an ethnic comparison of vecuronium in the three groups of patients encountered in Hong Kong military medical practice, namely Nepalese, Chinese and European

to include a study of the indigenous Nepalese in eastern Nepal.

Methods The study received ethics committee approval from the Army Medical Research Executive and the Research Ethics Committee of the Chinese University of Hong Kong and all patients gave written consent. There were 20 healthy adult patients (aged 18-55 years) in each group, namely indigenous Nepalese in Nepal, (NN); Ghurka soldiers (recruited in Nepal) and their dependents (Nepalese) posted to Hong Kong, (NH); indigenous Hong Kong Chinese soldiers, their dependants and civilians locally employed by the Ministry of Defence in Hong Kong, (CH) and, British servicemen, United Kingdom based civil servants and their dependants posted to Hong Kong, (EH). There were equal numbers of male and female patients in each group, who were selected consecutively from those scheduled for elective surgery where tracheal intubation using antidepolarising muscle relaxants was indicated. Those with known hepatic or renal disease were not studied. Anaemia did not debar patients from being included in the Nepal part of the study.

I.T. Houghton, LLB, FRCAnaes, Consultant in Anaesthesia and Resuscitation, British Military Hospital, Hong Kong and Honorary Lecturer, C.S.T. Aun, FRCAnaes, Senior Lecturer, T.E. Oh, FRCP (E.), FRCAnaes, FANZCA, Professor and Chairman, Department of Anaesthesia and Intensive Care, Dean, Faculty of Medicine, Chinese University of Hong Kong and Honorary Civilian Consultant Anaesthetist to the Army in Hong Kong. Correspondence should be addressed to Professor T.E. Oh, Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. Accepted 9 December 1991. 0003-2409/92/090741+ 06 $03.00/0

@ 1992 The Association of Anaesthetists of G t Britain and Ireland

741

142

I.T. Houghton, C.S.T. Aun and T.E. O h Table 1. Assessment of intubation by ethnic group.

Relaxation of jaw Excellent Satisfactory

Fair Poor

Relaxation of vocal cords

Overall assessment

Excellent (widely abducted) Satisfactory (slight movement of cords on intubation) Fair (moderate movement of cords, cough on intubation)

Excellent (no reaction)

Satisfactory (slight movement or bucking) Fair (moderate movement or bucking)

Poor

Poor

(cords adducted and held)

(intubation impossible)

All the anaesthetics (including the intubations) were given by the same anaesthetist (1.T.H) and comparable anaesthetic equipment and drugs were used in all cases. All patients received a standard anaesthetic. Premedication was with oral diazepam given approximately 1 h before the estimated time of surgery. Those weighing under 45 kg received Smg, those between 45 and 70 kg IOmg, and those over 70 kg 15 mg. Anaesthesia was induced with thiopentone in a dose not exceeding 5mg.kg-l body weight, given over approximately 20 s until loss of verbal response, and vecuronium (0.1 mg.kg-l) was given immediately following. Intubation was attempted a t exactly 60 s following the end of the injection of vecuronium and was assessed according to the scale in Table 1. The anaesthetics and assessment were carried out by the same anaesthetist (I.T.H.). Where the intubating conditions were poor or impossible, a further attempt was made 30 s later, at 90 s after injection of the vecuronium. If intubation was still difficult, another attempt was made 30 s later at 120 s. An increment of vecuronium (0.05 mg.kg-') was given after this to facilitate intubation, if required. A Magill folding laryngoscope with an adult Macintosh blade was used for the intubations with a Magill oral polyvinyl tracheal tube (Portex Ltd) of appropriate size. Anaesthesia was maintained with 70% nitrous oxide in oxygen plus enflurane 1.0-2.0% and was administered with a continuous flow anaesthesia machine using a coaxial breathing attachment. The lungs of all patients were mechanically ventilated, the ventilation being adjusted to keep the end-tidal concentration of carbon dioxide between 4.5 and 5.5 kPa. Neuromuscular function was monitored and further vecuronium (1-2 mg) was given as needed. The time and dose were recorded. At the end of surgery, the neuromuscular block was antagonised with neostigmine mixed with atropine. For the purpose of statistical analysis, grading of intubation at 60 s was categorised into satisfactory (excellent and satisfactory) and unsatisfactory (fair and poor). The patients' age, height, weight, skinfold thickness over the triceps and subscapular muscles and arm circumference were noted pre-operatively. All the skinfold thicknesses were measured with the same Lange skinfold calipers by the same investigator. Mean arm muscle circumference was calculated from the formula: Arm muscle circumference = Arm circumference-(3.14 x triceps skinfold) with all measurements in centimetres. Ideal anthropometric measurements were taken from Blackburn and colleagues [7]. Haemoglobin and biochemical tests for hepatic and renal functions were carried out in the respective laboratory

where the patients were located. Pulse and blood pressure were recorded using a noninvasive automztic recorder (Dinamap). Neuromuscular block of the ulnar nerve supplying the rn. abductor digiti rninirni was monitored with an anaesthesia and brain activity monitor (Datex, ABM) in Hong Kong and with a functionally similar neuromuscular transmission monitor (Datex, Relaxograph) in Nepal. Full relaxation was defined as t, = 0%. The hand and wrist were splinted and the forearm kept warm with a heat reflecting blanket. Oxygen and carbon dioxide concentrations in the circuit were measured with a carbon dioxide and oxygen analyser (Datex C D 102) in both locations. Analysis of variance was used for anthropometric data, drug dose and relaxant times, and Chi-squared tests for intubation data. For statistical analyses p < 0.05 was considered significant. All data are expressed as mean (SD) unless specified otherwise.

Results

Patient details and their demographic values (Table 2 ) show that the indigenous Nepalese (NN) are generally lighter and slimmer than the Nepalese, Chinese and Europeans in Hong Kong, although only the Europeans are significantly taller than the other groups. Eighty-five percent of patients in the NN group had unsatisfactory intubating conditions after the administration of vecuronium, whereas only 20% had unsatisfactory intubating conditions in the N H group. The proportion of satisfactory to unsatisfactory intubating conditions in the CH group (40%:60%) and the EH group (50%) were approximately equal. The differences were significant between the N N and the other groups ( p = 0.002) using contingency table analysis and Chi-squared test (Fig. I ) . The individual p values between groups were:

NN NH CH

NH

CH

0.001

> 0.05

-

0.004

-

-

EH

0.020 0.048

> 0.05

Following the administration of vecuronium, the times to full relaxation were shorter in the N N and EH groups than those in the N H and C H groups (Table 3). The duration of full relaxation in the N N group was shorter than the other three groups. None of these differences was statistically significant. The mean doses of thiopentone used were N N 4.55 (0.48) N H 4.21 (0.09) C H 4.30 (0.42) EH 4.13 (0.72)mg.kg-'. The

Anthropometric comparison of vecuronium

743

Table 2. Demographic data by ethnic group and sex. Values are expressed as mean (SD). Group

NN

NH

Mean age; years Combined 38.2 ( I 1.8)* Male 37.9 (11.3) Female 38.5 (12.2) Mean height; m Combined 1.56 (0.08) Male 1.61 (0.05) Female 1.51 (0.08) Mean weight; kg Combined 50.0 (7.7)' Male 49.7 (6.8) Female 50.2 (8.4) % ideal weight Combined 89.7 (14.5) Male 81.6 (11.0) Female 97.8 (12.9) Triceps skinfold; mm Combined 9.18 (4.54)* Male 6.13 (2.12) 12.23 (4.26) Female Subscapular skinfold; mm I I .24 (4.83)' Combined 9.13 (4.08) Male 13.34 (4.60) Female Mid arm circumference; m m Combined 239.8 (33.4)' Male 232.5 (36.9) Female 247.0 (27.7) Arm muscle circumference; mm Combined 210.9 (27.8)' Male 213.2 (32.6) Female 208.6 (21.8) % standard arm muscle circumference Combined 87.1 ( I 1.6) Male 84.3 (12.9) Female 89.9 (9.4) Surface area; m? Com bined 1.47 (0.13) Male 1.50 (0.10) Female 1.44 (0.14)

29.2 31.8 26.5

(5.1) (5.2) (3.5)

1.59 (0.06) 1.64 (0.03) 1.53 (0.03)

EH

CH 33.4 31.1 35.7

(6.3) (4.8) (6.8)

1.63 (0.09) 1.70 (0.06) 1.56 (0.04)

34.1 31.5 36.6

(8.9) (8.8) (8.2)

1.71 (0.12)' 1.81 (0.09) 1.62 (0.07)

All groups 33.7 33.1 34.3

(9.0) (8.5) (9.5)

1.62 (0.1 1) 1.69 (0.10) 1.56 (0.07)

63.0 (1 1.2) 67.6 (7.0) 58.5 (12.6)

60.2 (1 1.3) 68.2 (6.5) 52.3 (9.4)

73.3 (14.7)' 78.5 (12.2) 68.0 (15.0)

61.6 (14.2) 66.0 (13.4) 57.2 (13.6)

109.6 (18.2) 107.5 (9.3) I11.8 (23.7)

100.0 (14.3) 101.9 (9.5) 98.0 (17.6)

110.3 (21.8) 104.1 (12.7) 116.5 (26.6)

102.4 (19.3) 98.7 (14.7) 106.0 (22.5)

13.98 (5.84) 10.82 (3.92) 17.14 (5.73)

14.05 (6.23) 10.32 (3.10) 17.77 (6.35)

13.79 (6.44) 9.70 (2.57) 17.88 (6.55)

12.75 (6.16) 9.24 (3.52) 16.26 (6.24)

17.13 (8.23) 13.78 (5.53) 20.47 (9.08)

17.17 (6.24) 14.42 (4.20) 19.92 (6.72)

15.67 (7.19) 13.05 (3.57) 18.29 (8.77)

15.30 (7.16) 12.60 (4.86) 18.01 (8.02)

276.0 (42.2) 288.5 (18.5) 263.5 (54.0)

280.9 (33.1) 290.0 (15.3) 271.8 (42.3)

304.8 (42.7) 312.0 (27.1) 297.5 (53.2)

275.4 (44.7) 280.8 (39.1) 270.0 (49.0)

232.1 (39.0) 254.5 (10.6) 209.6 (43.8)

236.8 (29.2) 257.6 ( I 1.6) 216.0 (26.7)

261.4 (38.9) 281.5 (22.2) 241.3 (41.6)

235.3 (38.6) 251.7 (32.4) 218.9 (37.2)

95.5 (14.6) 100.6 (4.2) 90.4 (18.9)

97.4 (9.8) 101.8 (4.6) 93.1 (11.5)

107.6 (14.6) 111.3 (8.8) 104.0 (17.9)

96.9 (14.7) 99.5 (12.8) 94.3 (16.0)

1.64 (0.15) 1.73 (0.14) 1.55 (0.14)

1.64 (0.18) 1.79 (0.10) 1.49 (0.11)

1.85 (0.23) 1.98 (0.19) 1.72 (0.19)

1.65 (0.22) 1.75 (0.18) 1.55 (0.21)

For explanation of abbreviations see Legend to Figure I . 'represents difference is significant compared with all other groups ( p < 0.05).

percentage of smokers in the groups were NN 30%, N H lo%, CH 15% and EH 50%. Liver function tests were within normal limits in all four groups of patients, although the mean total bilirubin level

20

2 15 c -

+ a 0

b 10 L

m

n

5

2

5 n -

NN

NH

CH

Fig. 1. Ease of intubation by ethnic group at 60 s.

.,

EH

satisfactory; 0,unsatisfactory; NN. indigenous Nepalese in Nepal; NH, Ghurka soldiers and their dependants posted to Hong Kong; CH, indigenous Hong Kong Chinese soldiers, their dependants, and civilians employed by the Ministry of Defence; EH, British servicemen, UK based civil servants and dependants posted to Hong Kong.

in the NN group was 17.1 (2.1) mol.1-I compared with 14.4 ( I 1.0) rnol.1-l in the NH group, 11.2 mol.1-I in the CH group and 10.2 mo1.l-l in the EH group. The mean haemoglobin level of 12.7 g.100 ml-'(two patients having values of less than 1 0 g . l O O m l ~ l in ) the N N group was significantly lower than the range of 14.1-14.3 (1.4) g.lOOml-' in the other groups (p < 0.05). Gamma glutamyl transferase was 29.7 (22.6) IU in NH, 20.7 (1 1.0) IU in CH, and 30.4 (25.6) IU in EH. The data were further analysed by sex grouping. The women had significantly larger mean triceps and subscapular skinfold thicknesses, but their mean arm muscle circumference was less, being 94% of ideal (female) compared to 99% of ideal (male) for men (Table 2). The men had a mean percentage of ideal weight of 99 (15%) compared with the women's 106 (22%). The mean thiopentone dose was 4.26 mg.kg-' for males and 4.18 mg.kg-' for females. The ease of intubation conditions is displayed diagrammatically by race and sex in Figure 2. The females had better intubating conditions at 60 s after vecuronium (p < 0.004). There was no difference in either the time to full relaxation or the duration of relaxation between males and females (Table 4).

744

I.T. Houghton, C.S.T. Aun and T.E. Oh Table 3. Muscle relaxation. Time to reach full relaxation and duration of full relaxation by ethnic

group. Values are expressed as mean (SD). Group

Time to full relaxation; min Duration of full relaxation; min

NN

NH

CH

EH

3.9 (0.8) 16.8 (6.9)

4.4 (1.5) 21.2 (7.6)

4.7 (0.6) 20.8 (6.6)

3.8 (1.5) 23.5 (10.4)

For explanation of abbreviations see legend to Figure I . Table 4. Muscle relaxation. Time to reach full relaxation and duration of full relaxation by sex.

Values are expressed as mean (SD). NH

NN

CH

EH

All groups ~~

Time to full relaxation; min Male

3.86 (0.87)

3.75 (0.78)

Female 3.91 (0.73) 5.10 (1.66) Duration of full relaxation; min Male 14.4 (4.0) 23.2 (8.6) Female 19.2 (7.8) 19.2 (5.4)

4.50 (0.41) 4.95 (0.65) 23.3 (7.3) 18.9 (4.6)

4.05 (1.59) 3.55 (1.17) 20.9 (6.2) 26.1 (12.4)

4.03 (1.06) 4.40 (1.32) 20.4 (7.7) 20.0 (8.7)

For explanation of abbreviations see legend to Figure I . Thirty percent of males smoked compared to only 23% of the females.

Discussion This study shows that the Nepalese patients living in Nepal had less satisfactory intubating conditions at 60 s following the administration of vecuronium compared with Nepalese and other ethnic patients in Hong Kong. Our method of assessment was based on a study of intubation conditions by Clarke and Mirakhur [8]. Their assessment of intubations at 60 s after a dose of vecuronium 0.1 mg.kg-’ appeared to be a good combination to investigate and compare the sensitivity to vecuronium. It was impossible for observers to be blind, but we had a single assessor (I.T.H.) together with another observer in order to minimise the interobserver bias. We feel that our assessment is comparable with Clarke’s study: we saw a similar percentage of patients with satisfactory intubating conditions in our European and Chinese patients (50% European and 40% Chinese versus 40% in Clarke’s patients), whereas in the Nepalese patients, 80% in the Hong Kong (NH) group were satisfactory but only 15% in the Nepal (NN) group which, as is suggested later,

.,

Fig. 2. Ease of intubation by sex at 60s. satisfactory; 8 , unsatisfactory. Abbreviations as for Figure 1 and (M), male; (F)

female.

may be the result of differences in muscle mass and in the distribution volume of the muscle relaxant. Ease of tracheal intubation depends upon the degree of muscular relaxation, depth of anaesthesia and technical proficiency [9]. We measured neuromuscular transmission to the m. abductor digiri minimi electromyographically [lo]; there were no intergroup differences in the time to reach 100% block of neuromuscular transmission (4.2 (1.2) min). Casson and Jones [I I] showed, with a dose of vecuronium 0.1 mg.kg-l, a latent onset time of 74 (19) s and a manifest onset time of 85 (27) s. Agoston [12], Kreig and co-workers [13], and Mirakhur [I41 have suggested that vecuronium produces complete relaxation of the vocal cords when the hand muscles are only about 50% paralysed. It is possible that we may have accomplished intubation before the muscle relaxant was effective, but Clarke in his study had observed that intubating conditions after thiopentone could not be related to the onset of neuromuscular blockade [8]. Young, Clarke and Dundee [ 151 have suggested that thiopentone in a dose of 5mg.kg-’ produces sufficient jaw relaxation to permit laryngoscopy. The mean dose of thiopentone required in our study was less than 5 mg.kg-l in all the groups, although the Nepalese in Nepal (NN) were found to have received more thiopentone on a weight basis than the other groups. Goat and colleagues [I61 showed that the speed of muscle paralysis after injection of a muscle relaxant depended on muscle blood flow; and as tissue perfusion is inversely related to blood viscosity, alterations in blood viscosity may affect onset time [17]. Although patients in Nepal had a lower mean haemoglobin value, they had less satisfactory intubating conditions, which suggests that their anaemia did not significantly enhance the speed of onset of the muscle relaxant. Duvaldestin and Henzel showed that only 30% of vecuronium is bound to plasma proteins, mainly to albumen [ I81 and therefore the modest alterations in protein binding with age, sex, oral contraceptives and cyesis are unlikely to be associated with clinically important effects. The lower mean concentration of albumen in the N N group, which is within the normal clinical range, was unlikely to affect the action of vecuronium. We had equal numbers of males and females in the groups; none of the women were pregnant.

Anthropometric comparison of vecuronium The Nepalese studied in Nepal were significantly older but none was older than 53 years and therefore this is unlikely to be of clinical significance. d’Hollander and colleagues could show no difference in the sensitivity to vecuronium between patients aged less than 40 and those aged 40-60 years [ 191. The patient’s lungs were ventilated with 1 % enflurane in nitrous oxide and oxygen prior to intubation. Enflurane can potentiate vecuronium [20], but in the short time of less than 60 s before intubation it was unlikely to produce significant individual differences. There was no difference between mean onset time and mean duration of vecuronium between the males and females, but the women had significantly better intubating conditions. Thus, better intubating conditions were found both in women and in patients living in Hong Kong. This is similar to what Donati and Bevan [21] found in women with pancuronium, that the onset time of muscle relaxation was shorter, and they suggested that this could have been due to differences in distribution volume and body composition. Differences in sensitivity to muscle relaxants have been demonstrated in paediatric patients, with nondepolarising muscle relaxant requirements being age dependent. Meretoja [22] suggests that the more rapid effect of muscle relaxants in neonates and infants can be explained by changes in sensitivity, distribution volume and muscle mass. Extracellular fluid volume mirrors the distribution volume of muscle relaxants, but whilst this cannot be the sole explanation for any differences, changes in the body composition during growth could be the reason, because of the major changes in the fat and muscle compartments after the age of one year [23]. N o changes in sensitivity would be expected in adult patients but there are sex differences in muscle mass and there may have been a difference in distribution volume, with those living in Nepal having lower mean weights and skinfold thicknesses. A larger dose of muscle relaxant is needed when there is less fat and more muscle [22], a factor common to both males and the Nepalese in Nepal (NN). Katz and others compared the effects of tubocurarine and suxamethonium in patients in London (UK) and New York (USA) and found that the magnitude and duration of action of tubocurarine was less in patients living in London than in New York [3]. He then went on to study American servicemen stationed in England and found that they responded similar to patients in New York. In our study, we also found a geographical difference, but unlike Katz’s Americans, our Nepalese have altered their response on settling in Hong Kong. Although no anthropometric data were available on Katz’s patients, it is unlikely that American servicemen would have changed their standard of living with their ready access to the PX (military shopping facility for US sourced goods) and USAF Commissary (US Air Force facility for US sourced groceries, vegetables and meat) and therefore they would not have altered their anthropometric measurements significantly. In contrast, Nepal is a poor country with a very low standard of living and those who are recruited into the British Army become relatively wealthy and receive adequate nutrition, unlike the indigenous population. The increase in mean body weight, mean triceps skinfold thickness and mean arm muscle circumference of the N H group compared with the N N group suggests a considerable increase in both fat and muscle bulk in the N H group. This

145

could well affect the pharmacokinetics of vecuronium and hence the different response to vecuronium observed. Unfortunately, we were unable to determine the pharmacokinetics of vecuronium because of a lack of the necessary logistic facilities in Nepal. In conclusion, this study has suggested that anthropometric factors are associated with differences in the effect of vecuronium on early intubation. The need for different countries to undertake their own research into the effects of drugs on their own populations is borne out by this study. Further work on the influence of anthropometry on other muscle relaxants is suggested. Acknowledgments The work was performed at the British Military Hospital, Hong Kong and the British Military Hospital, Dharan, Nepal.* The authors thank all the operating theatre and laboratory staff who helped with the trial, and in particular, Colonel A.I. Booth, L/RAMC and Major J. Stone, RAMC who helped with the data collection and observations during anaesthesia. The military author is grateful to the Director General of Army Medical Services for permission to publish. References [I]KALOWW. Ethnic differences in drug metabolism. Clinical Pharmacokinetics 1982;I: 373400. H. On the geographical distribution of [2]STEEGMULLER pseudocholinesterase variants. Humangenetik 1975; 2 6 167-85. [3]KATZRL, NORMANJ, SEEDRF, CONRAD L. A comparison of the effects of suxamethonium and tubocurarine in patients in London and New York. British Journal of Anaesthesia 1969; 41: 1041-7. [4]LEVYG . Differences in effect of suxamethonium in London, Los Angeles and New York. British Journal of Anaesthesia 1970;42 979-80. [5]WALTSLF, DILLON JB. Clinical studies of the interaction between d-tubocurarine and succinylcholine. Anesthesiology 1969;31: 39-44, [6]INESON N, GUY PJ, BAILLIER. Response of the British Gurkha camp to the 1988 Nepal earthquake. In: 6th World Congress on Emergency and Disaster Medicine, Congress Abstracts Book 1. 1989: 84-5. GL, BISTRIANBR, MAINI BS, SCHLAMM HT, [7]BLACKBURN

SMITHMF. Nutritional and metabolic assessment of the hospitalized patient. Journal of Parenteral and Enteral Nutrition 1977; 1: 11-22. RSJ, MIRAKHURRK. Intubating conditions after [8]CLARKE vecuronium: a study of three doses and a comparison with suxamethonium and pancuronium. In: AGOSTONS , BOWMAN WC, MILLERRD, VIBY-MOGENSEN J, eds. Clinical experiences with Norcuron Org NC 45, (vecuronium bromide). Current

Clinical Practice Series 11, Amsterdam: Excerpta Medica, 1983: 145-9. [9]GERGISSD, SOKOLL MD, MEHTAM, KEMMOT~U 0, RUDD

GD. lntubation conditions after atracurium and suxamethonium. British Journal of Anaesthesia 1983; 55: 83S-6s. [lo]FWGH ND, KAY B, HEALYTEJ. Electromyography in anaesthesia. A comparison between two methods. Anaesthesia 1984;3 9 574-7. [ I I] CASSONWR, JONESRM. Vecuronium induced neuromuscular blockade. The effect of increasing dose on speed of onset. Anaesthesia 1986;41: 354-7. [I21 AGOSTONS, SALTP, NEWTON D, BENCINIA, BOOMSMAP, ERDMANN W. The neuromuscular blocking action of Org NC 45, a new pancuronium derivative, in anaesthetised *British Military Hospital, Dharan, closed on 31 December 1989.

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patients. A pilot study. British Journal of Anaesthesia 1980; 5 2 53s-9s. [I31 KREIG N, MAZUR L, BOOIJ LHDJ, CRUL JF. lntubating conditions and reversibility of a new non-depolarizing neuromuscular blocking agent, Org-NC 45. Acta Anaesthesiologica Scandinavica 1980; 2 4 423-5. [I41 MIRAKHUR RK, FERRE~ CJ, CLARKERSJ, BALIIM, DUNDEE JW. Clinical evaluation of Org N C 45. Brirish Journal I$ Anaesthesia 1983; 5 5 1 19-24. [I51 YOUNG HSA, CLARKE RSJ, DUNDEE JW. Intubating conditions with AH 8165 and suxamethonium. Anaesthesia 1975; 30:30-33. [I61 GOATVA, YEUNGML, BLAKENEY C, FELDMAN SA. The effect of blood flow upon the activity of gallamine triethiodide. British Journal of Anaesthesia 1976; 48: 69-73. [I71 GRAMSTAD L, LILLEAASEN P, MINSAASB. Onset time for alcuronium and pancuronium after cremophor-containing anaesthetics. Acta Anaesthesiologica Scandinavica I98 I ; 25: 484-6. [I81 DUVALDESTIN P, HENZEL D. Binding of tubocurarine,

fazadinium, pancuronium and Org N C 45 to serum proteins in normal man and in patients with cirrhosis. British Journal of Anaesthesia 1982; 54: 513-6. (191 D’HOLLANDER A, MASSAUXF, NEVELSTEEN M, AGOSTONS. Age-dependent dose-response relationship of Org N C 45 in anaesthetized patients. British Journal of Anaesthesia 1982; 54: 653-7. [20] MCINDEWAR IC, MARSHALLRJ. Interactions between the neuromuscular blocking drug Org NC45 and some anaesthetic, analgesic and antimicrobial agents. British Journal of Anaesthesia 1981; 5 3 785-92. [21] DONATIF, BEVANDR. The influence of patient’s sex, age and weight on pancuronium onset time. Canadian Anaesthetists’ Society Journal 1986; 3 3 S86. [22] MERETOJAOA. Neuromuscular blocking agents in paediatric patients: influence of age on the response. Anaesthesia and Intensive Care 1990; 1 8 440-8. [23] FRIIS-HANSEN B. Body composition during growth. In vivo measurements and biochemical data correlated to differential anatomical growth. Paediatrics 1971; 47: 26474.

Vecuronium: an anthropometric comparison.

This study set out to determine if there was any resistance to vecuronium in Nepalese studied in Nepal compared with Nepalese, Chinese and European pa...
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