Editorial II

Sedation and analgesia—which way is best?

G.R. Park

Practices vary in many areas of patient care, but one with a large degree of variability is the use of drugs to make patients comfortable—sedation and analgesia. Sedation and analgesia are common practice, with over 90% of patients in intensive care units (ICUs) needing them,1 and costing 0.8–1.2 billion dollars in 1997.2 The drugs used are potentially dangerous. Not only do they act on the central nervous system to reduce pain and suffering, but they also have many other effects.3 These effects are widespread and as yet poorly understood; an example is their effect on the immune system.46 What is clear is that if used carelessly, these drugs are a cause of morbidity, mortality and increased costs.

In these days of evidenced-based medicine, what is surprising is the large differences that exist between clinicians in using these drugs, even those working in the same ICU. Some of these differences may result from the background of the clinician. For example, physicians may lack some of the skills in regional analgesia possessed by anaesthetists, resulting in a greater use of parenteral opioids. Other reasons for the differences may involve availability (perhaps related to cost) or personal preference or prejudice. In this edition of the Journal, a group from Brussels7 describe a survey, using email, of sedative and analgesic practices that looks at differences in 16 countries across western Europe. This survey is interesting for two reasons: (i) the method by which it was done; and (ii) the large differences in international variation that were shown.

The use of e-mails to send a questionnaire is novel and makes a pleasant change from the four sheets of paper and the (sometimes) stamped addressed envelope often used for such an exercise. The e-mail addresses used by the authors were collected from various sources, including conferences, databases, etc. This does, however, mean that only those who routinely use e-mails were available to respond. Those not used to using e-mails are unlikely to give their e-mail addresses, even if they have one. Furthermore, the advent of free e-mail addresses has led to many people changing their e-mail addresses at regular intervals. In the Eastern Area Intensive Care Group in the UK, 15–20% of members change their e-mail address every 2 years (M. Blunt, personal communication). This may, in part, explain the rather low response rate (20%) seen in this survey.

A further reason for the low response rate may have been the questionnaire being treated as just another uninvited, unexpected e-mail (‘spam’) and so being deleted on receipt. With the ease and low cost of sending email questionnaires, this way of doing surveys is likely to become popular. The risk is that it may lead to a barrage of questionnaires about aspects of the way we treat patients. I have no doubt some will be valuable and others of less value; even the good ones may be deleted just because of the number that may arrive.

The paper showed intriguing, marked national variations in sedative and analgesic practice. There are many possible reasons for them. For example, sedation and analgesia have many components. Most of these, such as anxiety or perception of pain, have a very strong cultural overlay. Stoical Northern Europeans may respond to these stimuli differently from temperamentally different Southern Europeans. However, the 75% need for continuous intravenous sedation in patients needing mechanical ventilation in the UK compared with only 30% in Italy is difficult to explain on grounds of temperament alone. An alternative explanation is the availability and cost of drugs. Midazolam only became available in Italy in the last 3 years. Propofol usage would be expected to be high as a consequence. Similarly, sufentanil is not available in the UK while alfentanil is. The recent licensing of dexmedetomidine by the Food and Drug Administration in USA, but the delay of its licence by the European Licensing Authority, may result in some interesting differences in sedative and analgesic practice between the USA and Europe. The likely future licensing of remifentanil for use in the critically ill in Europe will accentuate these differences.

A further reason for the difference is cost. This has been recognized as an important feature of sedative and analgesic drugs. Recent presentations8 9 at the European Society of Intensive Care Meeting in October 2000 recognized the impact of new drugs in reducing these costs. Until recently, propofol was an expensive drug. This high cost may have influenced some countries in their choice of sedative and analgesic agents. If this is so, what is surprising is the high usage of propofol in the UK, a country with a relatively low expenditure on health care in Europe; perhaps it is a reflection of the large proportion of anaesthetists practicising intensive care in the UK.

This study,7 in common with many others and some clinicians, assumes that midazolam and propofol are different versions of the same drug. This is clearly not so. Propofol is extremely good at inducing sleep, while midazolam is better at producing anxiolysis and amnesia. Perhaps some of the differences shown in this study result from clinicians in some countries recognizing these differences while those in others do not.

One surprising feature is the low usage of lorazepam. According to the American Society of Critical Care Medicine Guidelines,10 lorazepam is the drug of choice for long-term sedation. It is inexpensive, thought to have inactive metabolites and is effective. Why, then, is it not used? There is some concern about the toxicity of the solvent, propylene glycol, which may inadvertently be given in large amounts with the potential risk of serious toxicity.11 However, this is an unlikely explanation. More likely is that the guidelines are just not being followed, a common feature in this area of critical care. Other guidelines have also been developed to help with sedation and analgesia. Bair and colleagues12 have looked at how well clinicians followed agreed guidelines about sedation. While the initial choice of drugs was as recommened in guidelines in 60% of patients, only guidelines were followed throughout a patient’s ICU stay for only 23% of patients. The reasons given for not following the protocol were patient variability, clinicians’ preference for other drugs and the guideline learning curve of residents. Why clinicians do not follow guidelines is an area of worthy study, since the introduction of guidelines has been shown to reduce significantly the mortality, morbidity and costs in this area.2 1316

One of the difficulties in applying guidelines about sedation and analgesia is their applicability to individual patients. Part of this difficulty is how the effects of these drugs are measured. As yet there is no magic black box that generates a number to say if the effects are adequate or not. Perhaps one day! The bispectral index (BIS) looks promising,17 but it is too early in its development to say how useful it will be. In the meantime we have to rely on clinical scales and scores.1822 These rarely have precise endpoints, unlike the measurement of heart rate or blood pressure used when giving catecholamines, or blood glucose concentration to guide insulin dosage. There are some measures of outcome, for example the Brussels group23 have shown a reduction in sedative needs when a score is introduced. It is surprising, therefore, that in some countries sedation scoring is so poorly used, with only one in five ICUs in Austria routinely using one.

Sedation and analgesia are complex subjects. Sedation and analgesia are universally practised in ICUs throughout the world but, surprisingly, we know little about them. This study adds yet more questions for investigators to answer. By trying to explain these differences, it is hoped that we will improve the comfort of our patients while reducing risks and costs.

G.R. Park

Addenbrooke's Hospital

Cambridgeshire CB2 2QQ, UK

References

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