1Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Route de Lennik 808, B-1070 Brussels, Belgium*Corresponding author
This article is accompanied by Editorial II.
Accepted for publication: January 16, 2001
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Abstract |
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Br J Anaesth 2001; 87: 18692
Keywords: analgesia; sedation; intensive care
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Introduction |
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The aim of our study was to assess differences in the clinical use of sedative and analgesic drugs, alone or in combination, in western European ICUs.
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Methods |
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Results |
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Sixty-three per cent of respondents said they used midazolam often or always in patients requiring sedation, and 35% used propofol (Table 3). Although midazolam was the most commonly used sedative drug in both medical and surgical units, the common (often or always) use of propofol was more frequent in surgical units than in medical units (34% and 12%, respectively; P<0.05); the reverse was true for midazolam (55% and 88%, respectively; P<0.05). There was a highly significant difference (P<0.01) in the use of midazolam and propofol between countries. Midazolam was often or always used by 85% of respondents in Norway, but only by 39% in Denmark, and propofol was often or always used by 65% of Italian respondents, but only by 3% of respondents from Norway (Figure 1). Midazolam was more commonly used than propofol in France, Germany, the Netherlands, Norway and Austria (P<0.05), and propofol appeared to be more commonly used than midazolam in Italy, and Belgium and Luxemburg, although this was not significant (Figure 1). Lorazepam was used often or always by only three (0.5%) respondents.
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Discussion |
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However, excessive sedation can have negative side-effects, including an increased risk of venous thrombosis, decreased intestinal motility, hypotension, reduced tissue oxygen extraction capabilities, prolonged ICU stay and increased costs.2630 An acute withdrawal syndrome following prolonged use of sedative or analgesic drugs has also been reported in ICU patients.31 Ideally, administration of sedative and analgesic drugs should aim to keep the patient comfortable but easily aroused.32 Attitudes may have changed over time, as suggested by two enquiries in the UK: in 1981, Merriman33 reported that 67% of ICUs aimed to keep patients completely detached from the environment, whereas by 1987, Bion and Ledingham noted that 69% of respondents preferred patients sleepy but easily awakened.14
In 1995, the Society of Critical Care Medicine (SCCM) published practice parameters for intravenous analgesia and sedation in the ICU.1 Evidence-based medicine recommendations regarding the preferred agents were developed by a task force of more than 40 experts. Midazolam and propofol were preferred for short-term sedation, lorazepam for long-term sedation and haloperidol for treating delirium, while morphine and fentanyl were the preferred analgesic agents in critically ill patients.1 Despite such guidelines, there are large differences in the use of sedative and analgesic agents among units and across national and international boundaries.1318 34 A survey of head nurses from 164 hospitals across the USA in 1991 found that 18 different sedative agents were used, with a preference for benzodiazepines and opiates.15 Also in the USA, Dasta and colleagues16 reported the use of 23 different agents for sedation and relief of anxiety and pain in their surgical ICU with extensive use of benzodiazepines (including, most commonly, lorazepam) and morphine. In our study, 22 different drugs were cited as being used often or always for sedation or analgesia, with midazolam, morphine and fentanyl generally being the preferred agents.
Benzodiazepines, e.g. diazepam, lorazepam and midazolam, are widely used as sedative agents in the ICU. Diazepam use has become less common as newer shorter-acting benzodiazepines have become available. Lorazepam is more potent than midazolam and, because of its low lipid solubility, crosses the bloodbrain barrier more slowly, delaying its onset of action and prolonging the sedative effect.6 35 Hence, it is recommended for longer-term sedation while midazolam is preferred for short-term sedation.1 Propofol, another frequently used sedative agent, resembles midazolam in terms of pharmacological profile.35 Studies comparing midazolam and propofol have generally shown the two agents to be of similar efficacy and safety in sedating various groups of critically ill patients.4 5 9 36 37 Midazolam is, however, cheaper than propofol,9 12 38 39 which may account for the preferred use of midazolam seen in our study and others.17 18 40 Nevertheless, some would argue that propofol, when used as a sedative in mechanically ventilated patients, is associated with shorter weaning times and hence, while midazolam may be cheaper, the overall costbenefit analysis taking into account duration of mechanical ventilation and ICU stay may in fact be better with propofol.2 8
We also found great differences in the drugs most commonly used for analgesia, although morphine and fentanyl were most commonly prescribed, a finding supported by other groups15 16 18 34 40 and in accord with the recommendations of the SCCM.1 Opioids, generally administered as a continuous intravenous infusion, remain the mainstay of ICU analgesia. Morphine is the most widely used of the opioids, possibly again related to its lower cost,38 although the shorter-acting fentanyl and sufentanil are preferred by some.
Importantly, sedative and analgesic drugs are distinct agents, having separate, although complementary and sometimes synergistic, actions.41 42 Combined use of these drugs is common in the ICU patient; Watling and colleagues34 reported that 25% of patients received combination drug therapy, 46% of whom received a benzodiazepineopiate combination. Magarey17 reported that, in Australia, the most common form of sedation was a benzodiazepineopiate combination (used in 88% of ICUs), notably morphine with midazolam. In our study, the particular combination of drugs differed among countries, with, for example, midazolam and fentanyl preferred in France, but midazolam and morphine preferred in Norway.
While it was not the aim of the questionnaire, it is interesting to speculate on the reasons behind the differences in sedative and analgesic use seen among western European countries. The costs of drug therapy are certainly important and international differences in drug price may exist as a result of individual pricing policies, costs of transport and packing, and the cost of the mark-up added to the price of drugs by the importer and distributor.43 Several groups have reported lorazepam to be an effective sedative agent with lower costs than midazolam or propofol,6 11 12 and yet lorazepam was used often or always by only three of our respondents.
Differences in the timing of drug registration in various countries may account for certain preferences. As an example, the fact that midazolam has only recently been registered in Italy may explain why propofol was used more than midazolam in Italy, while the fact that sufentanil is less easily available in the UK may explain why morphine and fentanyl were used more than sufentanil in the UK. The primary speciality of the intensivist questioned may also influence drug choice; for example, anaesthetists may favour anaesthetic agents more than intensivists with a general medical background. While the design of our questionnaire did not allow us to investigate this aspect specifically, it is interesting to note that propofol was used more frequently on surgical than on medical units, perhaps related to its common use as an anaesthetic agent. It may also be preferred to facilitate earlier weaning and extubation.3 12 Communication with patients by verbal and non-verbal methods, such as touch by staff or relatives, is very important and depends on individual cultural, educational and socio-economic differences.44 This may decrease the need for sedation, although it may not significantly affect the choice of agent.
Both under- and over-sedation can have negative effects on the ICU patient,10 and in this population, particularly those who are mechanically ventilated, the level of sedation is often difficult to assess. Various sedation scales and scores have been developed in order to facilitate this process,4550 and the use of a sedation scale has been shown to reduce the numbers of patients with excessive degrees of sedation.50 However, many units still rely on staff assessment of sedation rather than routinely employing any of the available scoring systems. Watling and colleagues34 reported that just 26% of the respondents in their survey of ICUs in the USA used a sedation scale, while Christensen and Thunedborg18 noted that only 16% of Danish ICUs used a sedation scoring system. In our study, we found that 43% of units used a scale, but this figure varied greatly among individual countries. As we report, the Ramsay scale45 is generally the most widely used sedation assessment system, probably chiefly because it is easy to apply, although it has never been scientifically tested for reliability or validity.51
In conclusion, our enquiry has revealed substantial international differences in the clinical use of drugs for sedation and analgesia in western European countries, and in the use of sedation scales to monitor levels of sedation. While we acknowledge the inherent limitations of questionnaire surveys and accept that the response rate was relatively low, we received replies from a broad cross-section of ICUs and hospital types, and have no reason to believe the data obtained are not representative of the current situation in western Europe. Such information can encourage valuable discussion about the reasons behind the variations seen, and perhaps help in the development of sedation and analgesic protocols, which have been shown to improve outcome.52
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