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Comparative use of muscle relaxants and their reversal in three European countries: a survey in France, Germany and Great Britain

Osmer, C.; Vogele, C.; Zickmann, B.; Hempelmann, G.

European Journal of Anaesthesiology: July 1996 - Volume 13 - Issue 4 - p 389-399
Original Papers
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A survey was conducted among British, French and German anaesthetists to evaluate possible national differences in the peri-operative use of muscle relaxants and their reversal agents. The same non-depolarizing relaxants are used in all three countries, with the exception of d-tubocurarine, which is only available in Great Britain, and alcuronium which is mainly used in Germany. The French anaesthetists seem to use significantly less succinylcholine than their peers in Great Britain or Germany for both elective and emergency intubation. Monitoring of neuromuscular blockade still relies mainly on 'clinical judgement'. Reversal of non-depolarizing muscle relaxants is performed routinely in Great Britain, while a substantial number of French anaesthetists avoid the use of a reversal. Dose regimes for neostigmine vary largely, with German anaesthetists administering the lowest, and British anaesthetists administering the highest doses. Side effects of reversal agents are reported by colleagues from all three countries in too high a percentage to justify uncritical administration of these drugs. In Germany there seems to be a noteworthy lack of recovery facilities.

Department of Anaesthetics and Surgical Intensive Care, Justus-Liebig-University, Giessen, Department of Psychology, Philipps-University, Marburg, Germany

Accepted January 1996

Correspondence: Dr Christian Osmer, Abteilung für Anaesthesiologie und Operative Intensivmedizin, Justus-Liebig-Universität, Rudolf-Buchcheim-Str., D-35392 Giessen, Germany.

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Introduction

Since the introduction of d-tubocurarine more than 50 years ago, neuromuscular blockade has become a well established part of balanced anaesthesia. But even though neuromuscular blockers have been in use for such a long time, and despite readily available references on the pharmacokinetic and pharmacodynamic properties of these drugs, many different 'local habits' seem to have evolved in clinical practice. As the European countries grow closer, and there is an increasing professional migration over language boundaries, it was considered of interest to investigate differences in the peri-operative use of neuromuscular blockers and their reversal agents in three European countries.

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Material and methods

A questionnaire was developed and sent to anaesthetists in France, Germany and Great Britain in order to evaluate the peri-operative use of neuromuscular blockers and cholinesterase inhibitors. In France and Germany, 100 anaesthetists were chosen at random out of the membership lists of the respective Associations of Anaesthetists (France: 'Société Française d'Anesthésie et de Réanimation', Germany: 'Berufsverband Deutscher Anästhesisten'), in Great Britain 80 questionnaires were distributed by the Royal College of Anaesthetists' tutor working in the SouthWest Thames Region.

The questions were to be answered on six point rating scales, giving six frequency ranks from 0 = 'never' (used) to 5 = 'always' (used). For each question, ratings were averaged within nations, resulting in a 'frequency index' as a measure of the frequency of the use of a certain drug or a certain procedure in that nation. These frequency indices were used to test for differences between nations using non-parametric statistical procedures. In a first analysis step, Kruskal-Wallis one-way analyses of variance were used to test for overall differences between the three countries. If the effect was significant, pairwise comparisons were carried out between countries using Mann-Whitney U-tests. The results of these paired tests are reported in the tables under the heading 'comparison between nations'.

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Results

The survey was conducted between April and June 1992. The return of the questionnaires was 80% for France, 75% for Germany and 45% for Great Britain. All of the British and French data were eligible for statistical analysis, four of the German questionnaires had to be discarded. The professional experience of the responders was on a high and comparable level, with 81% of the British anaesthetists being 'consultants' or 'senior registrars', 95% 'praticien hospitalier' or 'professeur' in France and 95% 'Facharzt für Anästhesie' in Germany.

As shown in Table 1, succinylcholine was the relaxant most commonly used in Great Britain (47%) and Germany (67%) for tracheal intubation in routine cases with no increased risk of regurgitation and aspiration of gastric contents. In contrast, 63% of the French anaesthetists reported never using this drug for elective tracheal intubation but preferred the intermediate acting, non-depolarizing neuromuscular blockers, or intubated the trachea without the help of a neuromuscular relaxant. The difference between France and the other two countries was statistically significant (Table 1).

Table 1

Table 1

In an emergency situation or with an anticipated increased risk of aspiration, succinylcholine was almost the only choice in Great Britain (97%) and Germany (90%), while in France it was used significantly less frequently: only 48% of the respondents reported using succinylcholine for that indication 'always' or 'most of the time'. French anaesthetists significantly more often reported the use of atracurium, vecuronium or intubated the trachea without any relaxant as valid alternatives to succinylcholine for emergency intubation (Table 2).

Table 2

Table 2

Peri-operatively, the same relaxants were used in all three countries, with d-tubocurarine being available only in Great Britain, and alcuronium mainly used in Germany. One German anaesthetist mentioned one 'other', unspecified relaxant; one French anaesthetist was still using gallamine (Fig. 1).

Fig. 1

Fig. 1

The timing of additional doses of the respective relaxant was mainly by the 'clinical judgement of the anaesthetist' in all three countries (Table 3). Only in Great Britain was a peripheral nerve stimulator used by a significantly higher number of the participating anaesthetists. A further question addressed the exact timing of additional muscle relaxant when monitoring with a nerve stimulator. Because this device was rarely used by anaesthetists in France and Germany, differences between nations could not be analysed. Therefore, frequency indices for the respective 'train-of-four' ratios are given without further interpretation (Fig. 2).

Table 3

Table 3

Fig. 2

Fig. 2

The use of a cholinesterase inhibitor at the end of surgery to reverse possible residual neuromuscular blockade was handled differently in the three participating countries. Many German and French anaesthetists did not routinely use a reversal agent after atracurium, vecuronium or pancuronium, the agent for post-operative reversal for all the neuromuscular blockers (see Table 4). Fifteen per cent of the French anaesthetists stated that they never gave a cholinesterase inhibitor at all - some of the participants in the survey explicitly noted this to be a 'policy of the department'.

Table 4

Table 4

Neostigmine was the cholinesterase inhibitor of choice in Great Britain and France. In Germany, 34% used neostigmine as their only cholinesterase inhibitor, but pyridostigmine (12%) and physostigmine (7%) were also mentioned as the single cholinesterase inhibitor of choice. The remaining German participants in this survey had two or all three of these cholinesterase inhibitors at their disposal, so that neostigmine was mentioned by a total of 62% of the respondents, pyridostigmine by 43% and physostigmine by 40% of the German participants.

The 'normal' and the 'maximum' dose of neostigmine given for an average, healthy adult patient of 70 kg varied considerably between the countries (see Table 5). The British questionnaires reported the highest 'normal' and 'maximum' doses for neostigmine with the smallest inter-individual variation. They were significantly higher than the reversal doses used in the other two countries. The neostigmine doses used in Germany were the smallest reported in this survey, with the French dose regime in between. While maximum doses of neostigmine could be as high as 5.0 mg in France and Great Britain, no single German anaesthetist reported using more than 2.5 mg of neostigmine.

Table 5

Table 5

The side effects attributable to cholinesterase inhibitors were also sought. The events had to be noticed by the respective anaesthetist and only in patients in whom an appropriate dose of an anticholinesterase had been given. Furthermore, the questionnaire asked whether any of the witnessed side effects needed therapeutic intervention at any time.

As shown in Table 6, there was no significant difference between the three countries in the frequency of cardiovascular side effects reported by the participating anaesthetists. 'Bronchial hyperactivity' had been observed significantly more often in France and Germany than in Great Britain, while 'increased gut motility' had a low frequency in all three countries. Even though a substantial number of the participating anaesthetists had witnessed untoward reactions to cholinesterase inhibitors which required intervention, the total was too small for statistical analysis.

Table 6

Table 6

Another question sought the reasons for with-holding a cholinesterase inhibitor at the end of an operation. There were no predetermined reasons to allow for national idiosyncrasies. The results are given in Table 7.

Table 7

Table 7

Recovery facilities for post-operative supervision of the patient were available for (almost) every patient in Great Britain and France, while in Germany only 36% of the participants had such facilities available for all routine cases Fig. 3.

Fig. 3

Fig. 3

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Discussion

Neuromuscular blocking agents and their antagonists are established components of balanced anaesthesia but it appears that there is a wide range of strategies for handling similar clinical situations. A survey was conducted therefore to identify current national differences in the peri-operative use of neuromuscular blockers and their reversal in a more systematic fashion.

Sample surveys have been a research tool in academic social science since the end of the 1950s, and they have also been used in medical research [1]. Among the available survey techniques the postal questionnaire can be a valuable source of information, provided certain precautions have been taken, such as an appropriately representative and up-to-date source of mailing addresses, a self-explanatory and easy to fill in questionnaire, and a reminder for nonresponders to send back their questionnaires [2]. Care was taken to construct this survey correctly.

Problems did arise because the survey was conducted in different countries, and especially the mode of distribution of the questionnaires was different in Great Britain compared with the other two countries. While the French and German questionnaires could be mailed directly to anaesthetists chosen at random from the respective membership lists of the French and German Societies of Anaesthetists, British questionnaires were distributed indirectly, i.e. by the Royal College of Anaesthetists tutors. Since the individual British participants were not known to the investigators, it was not possible to contact the British non-responders with a second letter to remind them to send back their questionnaires. This resulted in a lower over-all response rate from British anaesthetists. Nevertheless the response rate for Britain (45%) was acceptable, and the response rates for France (80%) and Germany (75%) were much higher than might be expected for such a postal survey [3]. The results reported in the current study cannot, therefore, be taken as a truly representative evaluation of the current opinion about neuromuscular blockade among anaesthetists in France, Germany and Great Britain. They do, however, indicate significant differences in clinical practice, within this study population.

The use of succinylcholine has recently been criticised, particularly when used in children, because of possible severe cardiovascular complications [4]. It is interesting, in this context, that while still being the routine relaxant for tracheal intubation in Germany and Great Britain, 78% of the French anaesthetists 'never' or 'rarely' used succinylcholine for elective tracheal intubation. The intermediate duration, nondepolarizing neuromuscular blockers seem to be a widely used alternative in France. The question arises, should the benefits and risks of succinylcholine be reevaluated in Britain and Germany? Even for tracheal intubation in an emergency situation or with the anticipated risk of aspiration, only 48% of the French respondents stated that they 'always' or 'most of the time' used succinylcholine. One has to keep in mind, though, that the majority of the participants in this survey had completed higher professional education and the figures may not represent the general approach to emergency tracheal intubation by anaesthetists in training.

Peri-operative monitoring of neuromuscular blockade is handled quite differently by anaesthetists in the three countries. Apparatus for monitoring the depth of neuromuscular blockade have been available for almost 20 years [5,6,7], and has become more easy to handle in the clinical setting. Also with the increasing use of intermediate neuromuscular blocking agents, there remains a risk of residual neuromuscular blockade at the end of surgery [8,9]. Insufficient recovery of muscular function after intra-operative neuromuscular blockade has been reported to be one reason for postoperative admission to an intensive care unit [10-12]. In spite of this, a majority of anaesthetists in all three countries relied on their 'clinical judgement' for the timing of additional doses of relaxant. Only in Great Britain is a peripheral nerve stimulator being used by a substantial number of anaesthetists.

Although many British anaesthetists monitor neuromuscular blockade intra-operatively, they use a reversal agent, even after using neuromuscular blockers such as vecuronium and atracurium. The incidence of residual block after these drugs is relatively low, while on the other hand there are inherent risks in giving reversal agents. (For a thorough review see [13].) In Britain, anaesthetists do not seem to be overly concerned about cardiac or pulmonary side effects when reversing neuromuscular blockade at the end of an operation, even though about 50% of them had witnessed unwanted effects of cholinesterase inhibitors at some time in their professional careers. At the other end of the spectrum, a substantial proportion of French anaesthetists explicitly stated that they never use a reversal agent. Many of them stated that it was a policy of their department to keep a patient ventilated post-operatively until full return of muscular strength.

We did not specifically ask for the reasons for either administering or withholding a reversal agent at the end of an operation, but the question arises as to what clinical guidelines are available for French and German anaesthetists when deciding reversal. Many studies have tried to correlate different bedside variables with TOF ratio and ventilatory tests [14,15,16]. However, the majority of these studies were performed in healthy, non-surgical young volunteers and it is therefore questionable whether one can rely on the result of a head lift test, the grip strength or the maximum inspiratory force before or after reversal of neuromuscular blockade when predicting a safe recovery in patients. Residual neuromuscular blockade as well as application of an anticholinesterase both have specific risks and it was not the aim of this survey to determine correct practice. However, the study does demonstrate two very different approaches to the same clinical situation with Great Britain on one side, and France and Germany on the other.

Possible problems in the immediate post-operative period are controlled by the close supervision guaranteed in France and Britain by the provision of recovery facilities. Noteworthy is the apparent lack of recovery beds in Germany. Complications caused by residual neuromuscular blockade or by recurarization might go unnoticed there.

There appears to be a difference in the 'observed effects' of cholinesterase inhibitors in Great Britain and the two other countries: while hypotension is the main complication seen in Britain, French and German anaesthetists point to arrhythmias and bronchial hypersecretion/bronchospasm as the main side effects seen after giving a reversal agent. The reason for this difference is not clear from the questionnaire. One possible explanation could be the use of different anticholinergic drugs with the cholinesterase inhibitor thus resulting in a different pharmacodynamic profile of both components of the reversal mixture. Another reason could be the different dose regimens for neostigmine in the three countries, especially in respect of bronchial side effects. One might speculate that with the dose of 0.5-1.0 mg given in Germany, the patients might have increased bronchial secretions but still have some residual neuromuscular block presenting bronchial clearing. Anaesthetists from the three participating countries stated that they had witnessed episodes of increased gut motility. After bowel surgery this can be a significant complication which, being mentioned by such a high percentage, prompts reconsideration of the routine use of reversal agents.

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Conclusions

Even though neuromuscular blockade is a well established component of balanced anaesthesia, there appear to be substantial national differences in the intra-operative use of these drugs. Considering that a large majority of the participants in this study had completed higher professional training, it may be assumed that there is more than one way to provide intra-operative relaxation. Nonetheless national preferences might be reconsidered by looking over the European borders.

Do we really have to use succinylcholine, taking the risks of malignant hyperthermia and severe cardiac complications? In view of many French colleagues abandoning the use of succinylcholine, even for emergency tracheal intubation, one might re-evaluate its indication in Britain and Germany and possibly restrict its use. Does a patient really need a reversal agent after an intermediate-duration non-depolarizing relaxant? With increased use of monitoring of neuromuscular function one might be able to tailor muscle paralysis to the individual situation and have the patient sufficiently recovered at the end of surgery. Is it plausible for the side effects of drugs to show a cross channel difference? Maybe we all tend to weigh such witnessed incidents rather subjectively and according to the tradition of our medical training and careers. Certainly, the situation regarding recovery facilities in Germany has to be improved, and the results from this study should be verified by future surveys. With Europe growing together, European anaesthetists should consider sharing knowledge and experience across national and language borders for the benefit of patients.

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Acknowledgments

The authors are grateful to Professor Dr H.-N. Herden, Head of the Anaesthetic Department, Altona General Hospital, Hamburg, as well as to Dr H. F. Seeley, Dean of Postgraduate Medical Education, British Postgraduate Medical Foundation, London and to Professor Dr J.-C. Otteni, Chef de Service, Service d'Anesthésie et de Réanimation, Hôpital de Hautepierre, Strasbourg for their encouragement and help in conducting this survey.

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References

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Keywords:

NEUROMUSCULAR RELAXANTS, neuromuscular blockade, cholinesterase-inhibitors, survey

© 1996 European Academy of Anaesthesiology