Sedative and analgesic practice in the intensive care unit: the results of a European survey
2001; Elsevier BV; Volume: 87; Issue: 2 Linguagem: Inglês
10.1093/bja/87.2.186
ISSN1471-6771
AutoresHend Soliman, Christian Mélot, Jean‐Louis Vincent,
Tópico(s)Cardiac, Anesthesia and Surgical Outcomes
ResumoSedation and analgesia are important aspects of patient care on the intensive care unit (ICU), yet relatively little information is available on common sedative and analgesic practice. We sought to assess international differences in the prescription of sedative and analgesic drugs in western European ICUs by means of a short, self-administered questionnaire. Six hundred and forty-seven intensive care physicians from 16 western European countries replied to the questionnaire. Midazolam was used as a sedative often or always by 63% of respondents and propofol by 35%. There were considerable international variations, with midazolam being preferred over propofol in France, Germany, the Netherlands, Norway and Austria. For analgesia, the drugs most commonly used were morphine (33%), fentanyl (33%) and sufentanil (24%). Morphine was preferred over fentanyl and sufentanil in Norway, UK and Ireland, Sweden, Switzerland, the Netherlands, and Spain and Portugal. Fentanyl was preferred in France, Germany and Italy. Sufentanil was preferred in Belgium and Luxemburg and in Austria. Multivariate analysis showed that the combination of midazolam with fentanyl was most often used in France; propofol with morphine in Sweden, the UK and Ireland, and Switzerland; midazolam with morphine in Norway; and propofol with sufentanil in Belgium and Luxemburg, Germany and Italy. The use of a sedation scale varied from 72% in the UK and Ireland to 18% in Austria. When used, the most common sedation scale was the Ramsay scale. This study demonstrates substantial international differences in sedative and analgesic practices in western European ICUs. Sedation and analgesia are important aspects of patient care on the intensive care unit (ICU), yet relatively little information is available on common sedative and analgesic practice. We sought to assess international differences in the prescription of sedative and analgesic drugs in western European ICUs by means of a short, self-administered questionnaire. Six hundred and forty-seven intensive care physicians from 16 western European countries replied to the questionnaire. Midazolam was used as a sedative often or always by 63% of respondents and propofol by 35%. There were considerable international variations, with midazolam being preferred over propofol in France, Germany, the Netherlands, Norway and Austria. For analgesia, the drugs most commonly used were morphine (33%), fentanyl (33%) and sufentanil (24%). Morphine was preferred over fentanyl and sufentanil in Norway, UK and Ireland, Sweden, Switzerland, the Netherlands, and Spain and Portugal. Fentanyl was preferred in France, Germany and Italy. Sufentanil was preferred in Belgium and Luxemburg and in Austria. Multivariate analysis showed that the combination of midazolam with fentanyl was most often used in France; propofol with morphine in Sweden, the UK and Ireland, and Switzerland; midazolam with morphine in Norway; and propofol with sufentanil in Belgium and Luxemburg, Germany and Italy. The use of a sedation scale varied from 72% in the UK and Ireland to 18% in Austria. When used, the most common sedation scale was the Ramsay scale. This study demonstrates substantial international differences in sedative and analgesic practices in western European ICUs. Anxiety and pain are commonly encountered by intensive care unit (ICU) patients, and almost all critically ill patients, particularly those receiving mechanical ventilation, will receive either a sedative or analgesic agent; many will receive both. A wide variety of pharmacological agents are now available for sedation and analgesia and, while recommendations have been made regarding the 'best' sedative and analgesic regimes for ICU patients,1Shapiro BA Warren J Egol AB et al.Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.Crit Care Med. 1995; 23: 1596-1600Crossref PubMed Scopus (349) Google Scholar practice varies widely between and within ICUs. The choice of agent can be based on many factors, including the relative needs for sedation and analgesia, the pharmacodynamics and pharmacokinetics of the drug in question, route and ease of administration, the tolerance profile and the cost. While many studies have been conducted comparing the effectiveness of various agents,2Carrasco G Molina R Costa J Soler JM Cabre L Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost–benefit analysis.Chest. 1993; 103: 557-564Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar, 3Polster MR Gray PA O'Sullivan G McCarthy RA Park GR Comparison of the sedative and amnesic effects of midazolam and propofol.Br J Anaesth. 1993; 70: 612-616Crossref PubMed Scopus (69) Google Scholar, 4Ronan KP Gallagher TJ George B Hamby B Comparison of propofol and midazolam for sedation in intensive care unit patients.Crit Care Med. 1995; 23: 286-293Crossref PubMed Scopus (135) Google Scholar, 5Kress JP O'Connor MF Pohlman AS et al.Sedation of critically ill patients during mechanical ventilation. A comparison of propofol and midazolam.Am J Respir Crit Care Med. 1996; 153: 1012-1018Crossref PubMed Scopus (147) Google Scholar, 6Cernaianu AC DelRossi AJ Flum DR et al.Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost.Crit Care Med. 1996; 24: 222-228Crossref PubMed Scopus (53) Google Scholar, 7Chamorro C de Latorre FJ Montero A et al.Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial.Crit Care Med. 1996; 24: 932-939Crossref PubMed Scopus (160) Google Scholar, 8Barrientos-Vega R Mar S Morales-Garcia C Robas-Gomez A Cuena-Boy R Ayensa-Rincon A Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs.Crit Care Med. 1997; 25: 33-40Crossref PubMed Scopus (272) Google Scholar, 9Weinbroum AA Halpern P Rudick V Sorkine P Freedman M Geller E Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison.Intensive Care Med. 1997; 23: 1258-1263Crossref PubMed Scopus (123) Google Scholar, 10Shafer A Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens.Crit Care Med. 1998; 26: 947-956Crossref PubMed Scopus (201) Google Scholar, 11Swart EL van Schijndel RJ van Loenen AC Thijs LG Continuous infusion of lorazepam versus midazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective.Crit Care Med. 1999; 27: 1461-1465Crossref PubMed Scopus (77) Google Scholar, 12McCollam JS O'Neil MG Norcross ED Byrne TK Reeves ST Continuous infusions of lorazepam, midazolam, and propofol for sedation of the critically ill surgery trauma patient: a prospective, randomized comparison.Crit Care Med. 1999; 27: 2454-2458Crossref PubMed Scopus (70) Google Scholar there is relatively little published information on variations in sedative and analgesic drug use among units or across national and international boundaries.13Merriman HM The techniques used to sedate ventilated patients. A survey of methods used in 34 ICUs in Great Britain.Intensive Care Med. 1981; 7: 217-224Crossref PubMed Google Scholar, 14Bion JF Ledingham IM Sedation in intensive care—a postal survey.Intensive Care Med. 1987; 13: 215-216PubMed Google Scholar, 15Hansen-Flaschen JH Brazinsky S Basile C Lanken PN Use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation for respiratory failure. A national survey.J Am Med Assoc. 1991; 266: 2870-2875Crossref PubMed Scopus (292) Google Scholar, 16Dasta JF Fuhrman TM McCandles C Patterns of prescribing and administering drugs for agitation and pain in patients in a surgical intensive care unit.Crit Care Med. 1994; 22: 974-980Crossref PubMed Scopus (87) Google Scholar, 17Magarey JM Sedation of adult critically ill ventilated patients in intensive care units: a national survey.Aust Crit Care. 1997; 10: 90-93Abstract Full Text PDF PubMed Scopus (40) Google Scholar, 18Christensen BV Thunedborg LP Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs 1996/97. A national survey.Intensive Care Med. 1999; 25: 186-191Crossref PubMed Scopus (75) Google Scholar 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. A short questionnaire was sent by e-mail to all names on a database, obtained from the European Society of Intensive Care Medicine, Intensive Care Symposium activities and other academic meetings, of ICU doctors in 17 western European countries: Belgium, Luxemburg, France, Germany, Netherlands, UK, Ireland, Finland, Denmark, Switzerland, Spain, Portugal, Greece, Italy, Austria, Sweden and Norway. The short questionnaire (Table 1) asked seven questions about the clinical use of sedative and analgesic drugs in ICU patients. Of the 3639 e-mail addresses, 340 were found to be incorrect and the messages were returned.Table 1Questionnaire used in studyNAME: ………………………COUNTRY: ………………………1.In your ICU, what percentage of mechanically ventilated patients require continuous i.v. sedation?□ <50%□ 50–75%□ 75–90%□ 100%2.In patients requiring a continuous infusion of sedative agents, how often do you use the following agents?midazolam:□ never□ seldom□ regularly□ often□ alwayspropofol:□ never□ seldom□ regularly□ often□ alwaysother (please specify):□ never□ seldom□ regularly□ often□ always3.What other intravenous sedative agents do you use regularly?haloperidol:□ never□ seldom□ regularly□ oftenother (please specify):□ never□ seldom□ regularly□ often4.Do you use a sedation score?□ yes□ noIf yes, what type?:□ Ramsay score□ locally developed score□ SAS score□ other5.In patients requiring continuous infusion of analgesic agents, how often do you use the following agents?morphine:□ never□ seldom□ regularly□ often□ alwaysfentanyl:□ never□ seldom□ regularly□ often□ alwayssufentanil:□ never□ seldom□ regularly□ often□ always6.Type of ICU (several answers possible)□ medical□ surgical□ trauma□ coronary□ paediatric□ burns7.Type of hospital (one answer)□ university/academic□ city□ community Open table in a new tab The answers were collected on a computer database. Univariate statistical analysis consisted of χ2 tests or Fisher's exact tests. Multivariate statistical analysis was also performed, using multiple correspondence analysis. The level of statistical significance was set at P 75% of their ventilated patients required continuous intravenous sedation while in Italy the figure was just 30%. 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.Table 3Prevalence of frequent use (often or always) of sedative and analgesic drugs. *Used regularly or often.Sedative drugNumber (%)Analgesic drugNumber (%)Midazolam408 (63)Morphine214 (33)Propofol229 (35)Fentanyl214 (33)Haloperidol*58 (9)Sufentanil153 (24)Clonidine12 (1.8)Piritramide5 (0.7)Ketamine8 (1.2)Others7 (1)Flunitrazepam6 (0.9)Droperidol5 (0.7)Alfentanil5 (0.7)Lorazepam3 (0.5)Diazepam2 (0.3)Methohexital2 (0.3) Open table in a new tab Thirty-three per cent of respondents stated that they used morphine often or always in patients requiring continuous intravenous analgesia, 33% said they used fentanyl and 24% sufentanil (Table 3), with significant differences among countries. The common (often or always) use of morphine varied from 88% in Norway to 3% in Germany, that of fentanyl from 58% in Italy to 0% in the Netherlands, and that of sufentanil from 52% in Belgium and Luxemburg to 0% in Switzerland. Morphine was used more commonly than the other agents in the UK and Ireland, Sweden, Norway, Switzerland, Spain and Portugal, and the Netherlands (P<0.05). Fentanyl was preferred over the other agents in France, Germany and Italy (P<0.05), and sufentanil was preferred in Belgium and Luxemburg, and Austria (P<0.05) (Figure 2). There was no significant difference in the use of analgesic drugs between different types of ICU. Multivariate analysis showed that the combination of midazolam and fentanyl was most often used in France, and that the combination of propofol and morphine was most used in Sweden, the UK and Ireland, and Switzerland. The combination of midazolam with morphine was most often used in Norway. The combination of propofol and sufentanil was most often used in Belgium and Luxemburg, Germany, and Italy (Figure 3). The use of a sedation scale varied widely (P<0.01) around a mean of 43% (Figure 4), with doctors from the UK and Ireland most frequently using a sedation scale (72%), and those in Austria using one least often (18%). When a sedation scale was used, the Ramsay scale was employed most commonly (74% of cases). The ICU environment can appear hostile, even threatening, to patients; the noisy ICU environment, unfamiliar monitoring and support equipment, medical jargon, loss of day–night cycle and painful invasive procedures are associated with a high incidence of psychological problems and sleep deprivation.19Lloyd GG Psychological problems and the intensive care unit.Br Med J. 1993; 307: 458-459Crossref PubMed Scopus (27) Google Scholar, 20Meyer TJ Eveloff SE Bauer MS Schwartz WA Hill NS Millman RP Adverse environmental conditions in the respiratory and medical ICU settings.Chest. 1994; 105: 1211-1216Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar, 21Schwab RJ Disturbances of sleep in the intensive care unit.Crit Care Clin. 1994; 10: 681-694Abstract Full Text PDF PubMed Google Scholar Sedation and analgesia are important to ensure patient comfort, from both psychological and physical points of view. The stress response can lead to profound changes in endocrine function, hypermetabolism, sodium and water retention, mobilization of substrates from energy stores and increased lipolysis.22Koepke JP Effect of environmental stress on neural control of renal function.Mineral Electrolyte Metab. 1989; 15: 83-87PubMed Google Scholar 23Roth-Isigkeit A Brechmann J Dibbelt L Sievers HH Raasch W Schmucker P Persistent endocrine stress response in patients undergoing cardiac surgery.J Endocrinol Invest. 1998; 21: 12-19Crossref PubMed Scopus (45) Google Scholar Pain can have many adverse consequences, including sympathetic overactivity with an increase in heart rate and myocardial oxygen consumption, increased respiratory rate and hypoxaemia, altered gastrointestinal motility, impaired urinary tract function, changes in blood viscosity, clotting time and platelet aggregation, diminished immune function and impaired wound healing.24Bonica JJ Importance of effective pain control.Acta Anaesthesiol Scand Suppl. 1987; 85: 1-16Crossref PubMed Scopus (46) Google Scholar 25Lewis KS Whipple JK Michael KA Quebbeman EJ Effect of analgesic treatment on the physiological consequences of acute pain.Am J Hosp Pharm. 1994; 51: 1539-1554PubMed Google Scholar 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.26Burns AM Shelly MP Park GR The use of sedative agents in critically ill patients.Drugs. 1992; 43: 507-515Crossref PubMed Scopus (77) Google Scholar, 27Van der Linden P Vincent JL The effects of sedative agents.in: Edwards D Shoemaker E Vincent JL Oxygen Transport: Principles and Practice. Ballière Tindall, London1993: 209-225Google Scholar, 28Durbin Jr, CG Sedation in the critically ill patient.New Horiz. 1994; 2: 64-74PubMed Google Scholar, 29Bosscha K Nieuwenhuijs VB Vos A Samsom M Roelofs JM Akkermans LM Gastrointestinal motility and gastric tube feeding in mechanically ventilated patients.Crit Care Med. 1998; 26: 1510-1517Crossref PubMed Scopus (87) Google Scholar, 30Kollef MH Levy NT Ahrens TS Schaiff R Prentice D Sherman G The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation.Chest. 1998; 114: 541-548Abstract Full Text Full Text PDF PubMed Scopus (738) Google Scholar An acute withdrawal syndrome following prolonged use of sedative or analgesic drugs has also been reported in ICU patients.31Cammarano WB Pittet JF Weitz S Schlobohm RM Marks JD Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients.Crit Care Med. 1998; 26: 676-684Crossref PubMed Scopus (238) Google Scholar Ideally, administration of sedative and analgesic drugs should aim to keep the patient comfortable but easily aroused.32Tung A Rosenthal M Patients requiring sedation.Crit Care Clin. 1995; 11: 791-803Abstract Full Text PDF PubMed Google Scholar Attitudes may have changed over time, as suggested by two enquiries in the UK: in 1981, Merriman33Merriman HM The techniques used to sedate ventilated patients. A survey of methods used in 34 ICUs in Great Britain.Intensive Care Med. 1981; 7: 217-224Crossref PubMed Scopus (114) Google Scholar 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.14Bion JF Ledingham IM Sedation in intensive care—a postal survey.Intensive Care Med. 1987; 13: 215-216PubMed Google Scholar In 1995, the Society of Critical Care Medicine (SCCM) published practice parameters for intravenous analgesia and sedation in the ICU.1Shapiro BA Warren J Egol AB et al.Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.Crit Care Med. 1995; 23: 1596-1600Crossref PubMed Scopus (349) Google Scholar 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.1Shapiro BA Warren J Egol AB et al.Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.Crit Care Med. 1995; 23: 1596-1600Crossref PubMed Scopus (349) Google Scholar Despite such guidelines, there are large differences in the use of sedative and analgesic agents among units and across national and international boundaries.13Merriman HM The techniques used to sedate ventilated patients. A survey of methods used in 34 ICUs in Great Britain.Intensive Care Med. 1981; 7: 217-224Crossref PubMed Google Scholar, 14Bion JF Ledingham IM Sedation in intensive care—a postal survey.Intensive Care Med. 1987; 13: 215-216PubMed Google Scholar, 15Hansen-Flaschen JH Brazinsky S Basile C Lanken PN Use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation for respiratory failure. A national survey.J Am Med Assoc. 1991; 266: 2870-2875Crossref PubMed Scopus (292) Google Scholar, 16Dasta JF Fuhrman TM McCandles C Patterns of prescribing and administering drugs for agitation and pain in patients in a surgical intensive care unit.Crit Care Med. 1994; 22: 974-980Crossref PubMed Scopus (87) Google Scholar, 17Magarey JM Sedation of adult critically ill ventilated patients in intensive care units: a national survey.Aust Crit Care. 1997; 10: 90-93Abstract Full Text PDF PubMed Scopus (40) Google Scholar, 18Christensen BV Thunedborg LP Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs 1996/97. A national survey.Intensive Care Med. 1999; 25: 186-191Crossref PubMed Scopus (75) Google Scholar 34Watling SM Dasta JF Seidl EC Sedatives, analgesics, and paralytics in the ICU.Ann Pharmacother. 1997; 31: 148-153Crossref PubMed Scopus (69) Google Scholar 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.15Hansen-Flaschen JH Brazinsky S Basile C Lanken PN Use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation for respiratory failure. A national survey.J Am Med Assoc. 1991; 266: 2870-2875Crossref PubMed Scopus (292) Google Scholar Also in the USA, Dasta and colleagues16Dasta JF Fuhrman TM McCandles C Patterns of prescribing and administering drugs for agitation and pain in patients in a surgical intensive care unit.Crit Care Med. 1994; 22: 974-980Crossref PubMed Scopus (87) Google Scholar 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 blood–brain barrier more slowly, delaying its onset of action and prolonging the sedative effect.6Cernaianu AC DelRossi AJ Flum DR et al.Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost.Crit Care Med. 1996; 24: 222-228Crossref PubMed Scopus (53) Google Scholar 35Young C Knudsen N Hilton A Reves JG Sedation in the intensive care unit.Crit Care Med. 2000; 28: 854-866Crossref PubMed Scopus (132) Google Scholar Hence, it is recommended for longer-term sedation while midazolam is preferred for short-term sedation.1Shapiro BA Warren J Egol AB et al.Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.Crit Care Med. 1995; 23: 1596-1600Crossref PubMed Scopus (349) Google Scholar Propofol, another frequently used sedative agent, resembles midazolam in terms of pharmacological profile.35Young C Knudsen N Hilton A Reves JG Sedation in the intensive care unit.Crit Care Med. 2000; 28: 854-866Crossref PubMed Scopus (132) Google Scholar 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.4Ronan KP Gallagher TJ George B Hamby B Comparison of propofol and midazolam for sedation in intensive care unit patients.Crit Care Med. 1995; 23: 286-293Crossref PubMed Scopus (135) Google Scholar 5Kress JP O'Connor MF Pohlman AS et al.Sedation of critically ill patients during mechanical ventilation. A comparison of propofol and midazolam.Am J Respir Crit Care Med. 1996; 153: 1012-1018Crossref PubMed Scopus (147) Google Scholar 9Weinbroum AA Halpern P Rudick V Sorkine P Freedman M Geller E Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison.Intensive Care Med. 1997; 23: 1258-1263Crossref PubMed Scopus (123) Google Scholar 36Snellen F Lauwers P Demeyere R Byttebier G Van Aken H The use of midazolam versus propofol for short-term sedation following coronary artery bypass grafting.Intensive Care Med. 1990; 16: 312-316Crossref PubMed Scopus (74) Google Scholar 37Sanchez IRJ Caballero-Cubedo RE Perez-Vela JL Ambros-Checa A Cantalapiedra-Santiago JA Alted-Lopez E Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient.Anesth Analg. 1998; 86: 1219-1224PubMed Google Scholar Midazolam is, however, cheaper than propofol,9Weinbroum AA Halpern P Rudick V Sorkine P Freedman M Geller E Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison.Intensive Care Med. 1997; 23: 1258-1263Crossref PubMed Scopus (123) Google Scholar 12McCollam JS O'Neil MG Norcross ED Byrne TK Reeves ST Continuous infusions of lorazepam, midazolam, and propofol for sedation of the critically ill surgery trauma patient: a prospective, randomized comparison.Crit Care Med. 1999; 27: 2454-2458Crossref PubMed Scopus (70) Google Scholar 38Armstrong DK Crisp CB Pharmacoeconomic issues of sedation, analgesia, and neuromuscular blockade in critical care.New Horiz. 1994; 2: 85-93PubMed Google Scholar 39Ostermann ME Keenan SP Seiferling RA Sibbald WJ Sedation in the intensive care unit: a systematic review.J Am Med Assoc. 2000; 283: 1451-1459Crossref PubMed Scopus (333) Google Scholar which may account for the preferred use of midazolam seen in our study and others.17Magarey JM Sedation of adult critically ill ventilated patients in intensive care units: a national survey.Aust Crit Care. 1997; 10: 90-93Abstract Full Text PDF PubMed Scopus (40) Google Scholar 18Christensen BV Thunedborg LP Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs 1996/97. A national survey.Intensive Care Med. 1999; 25: 186-191Crossref PubMed Scopus (75) Google Scholar 40Sun X Weissman C The use of analgesics and sedatives in critically ill patients: physicians' orders versus medications administered.Heart Lung. 1994; 23: 169-176PubMed Google Scholar 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 cost–benefit analysis taking into account duration of mechanical ventilation and ICU stay may in fact be better with propofol.2Carrasco G Molina R Costa J Soler JM Cabre L Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost–benefit analysis.Chest. 1993; 103: 557-564Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar 8Barrientos-Vega R Mar S Morales-Garcia C Robas-Gomez A Cuena-Boy R Ayensa-Rincon A Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs.Crit Care Med. 1997; 25: 33-40Crossref PubMed Scopus (272) Google Scholar 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 groups15Hansen-Flaschen JH Brazinsky S Basile C Lanken PN Use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation for respiratory failure. A national survey.J Am Med Assoc. 1991; 266: 2870-2875Crossref PubMed Scopus (292) Google Scholar 16Dasta JF Fuhrman TM McCandles C Patterns of prescribing and administering drugs for agitation and pain in patients in a surgical intensive care unit.Crit Care Med. 1994; 22: 974-980Crossref PubMed Scopus (87) Google Scholar 18Christensen BV Thunedborg LP Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs 1996/97. A national survey.Intensive Care Med. 1999; 25: 186-191Crossref PubMed Scopus (75) Google Scholar 34Watling SM Dasta JF Seidl EC Sedatives, analgesics, and paralytics in the ICU.Ann Pharmacother. 1997; 31: 148-153Crossref PubMed Scopus (69) Google Scholar 40Sun X Weissman C The use of analgesics and sedatives in critically ill patients: physicians' orders versus medications administered.Heart Lung. 1994; 23: 169-176PubMed Google Scholar and in accord with the recommendations of the SCCM.1Shapiro BA Warren J Egol AB et al.Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.Crit Care Med. 1995; 23: 1596-1600Crossref PubMed Scopus (349) Google Scholar 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,38Armstrong DK Crisp CB Pharmacoeconomic issues of sedation, analgesia, and neuromuscular blockade in critical care.New Horiz. 1994; 2: 85-93PubMed Google Scholar 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.41Gilliland HE Prasad BK Mirakhur RK Fee JP An investigation of the potential morphine sparing effect of midazolam.Anaesthesia. 1996; 51: 808-811Crossref PubMed Scopus (38) Google Scholar 42Carrasco G Cabre L Sobrepere G et al.Synergistic sedation with propofol and midazolam in intensive care patients after coronary artery bypass grafting.Crit Care Med. 1998; 26: 844-851Crossref PubMed Scopus (87) Google Scholar Combined use of these drugs is common in the ICU patient; Watling and colleagues34Watling SM Dasta JF Seidl EC Sedatives, analgesics, and paralytics in the ICU.Ann Pharmacother. 1997; 31: 148-153Crossref PubMed Scopus (69) Google Scholar reported that 25% of patients received combination drug therapy, 46% of whom received a benzodiazepine–opiate combination. Magarey17Magarey JM Sedation of adult critically ill ventilated patients in intensive care units: a national survey.Aust Crit Care. 1997; 10: 90-93Abstract Full Text PDF PubMed Scopus (40) Google Scholar reported that, in Australia, the most common form of sedation was a benzodiazepine–opiate 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.43Park GR Drugs used to make critically ill patients comfortable.Curr Opin Crit Care. 1999; 5: 249-250Crossref Scopus (2) Google Scholar Several groups have reported lorazepam to be an effective sedative agent with lower costs than midazolam or propofol,6Cernaianu AC DelRossi AJ Flum DR et al.Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost.Crit Care Med. 1996; 24: 222-228Crossref PubMed Scopus (53) Google Scholar 11Swart EL van Schijndel RJ van Loenen AC Thijs LG Continuous infusion of lorazepam versus midazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective.Crit Care Med. 1999; 27: 1461-1465Crossref PubMed Scopus (77) Google Scholar 12McCollam JS O'Neil MG Norcross ED Byrne TK Reeves ST Continuous infusions of lorazepam, midazolam, and propofol for sedation of the critically ill surgery trauma patient: a prospective, randomized comparison.Crit Care Med. 1999; 27: 2454-2458Crossref PubMed Scopus (70) Google Scholar 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.3Polster MR Gray PA O'Sullivan G McCarthy RA Park GR Comparison of the sedative and amnesic effects of midazolam and propofol.Br J Anaesth. 1993; 70: 612-616Crossref PubMed Scopus (69) Google Scholar 12McCollam JS O'Neil MG Norcross ED Byrne TK Reeves ST Continuous infusions of lorazepam, midazolam, and propofol for sedation of the critically ill surgery trauma patient: a prospective, randomized comparison.Crit Care Med. 1999; 27: 2454-2458Crossref PubMed Scopus (70) Google Scholar 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.44Vincent JL Communication in the ICU.Intensive Care Med. 1997; 23: 1093-1098Crossref PubMed Scopus (24) Google Scholar 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,10Shafer A Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens.Crit Care Med. 1998; 26: 947-956Crossref PubMed Scopus (201) Google Scholar 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,45Ramsay MAE Savage TM Simpson BRJ Goodwin R Controlled sedation with alphaxalone–alphadolone.Br Med J. 1974; ii: 656-659Crossref Scopus (2239) Google Scholar, 46Chernik DA Gillings D Laine H et al.Validity and reliability of Observer's Assessment of Alertness/Sedation Scale. Study with intravenous midazolam.J Clin Psychopharmacol. 1990; 10: 244-247Crossref PubMed Google Scholar, 47Wang DY Pomfrett CJ Healy TE Respiratory sinus arrhythmia: a new, objective sedation score.Br J Anaesth. 1993; 71: 354-358Crossref PubMed Scopus (35) Google Scholar, 48Riker RR Picard JT Fraser GL Prospective evaluation of the Sedation–Agitation Scale for adult critically ill patients.Crit Care Med. 1999; 27: 1325-1329Crossref PubMed Scopus (725) Google Scholar, 49Devlin JW Boleski G Mlynarek M et al.Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit.Crit Care Med. 1999; 27: 1271-1275Crossref PubMed Scopus (288) Google Scholar, 50Detriche O Berre J Massaut J Vincent JL The Brussels sedation scale: use of a simple clinical sedation scale can avoid excessive sedation in patients undergoing mechanical ventilation in the intensive care unit.Br J Anaesth. 1999; 83: 698-701Abstract Full Text PDF PubMed Scopus (45) Google Scholar and the use of a sedation scale has been shown to reduce the numbers of patients with excessive degrees of sedation.50Detriche O Berre J Massaut J Vincent JL The Brussels sedation scale: use of a simple clinical sedation scale can avoid excessive sedation in patients undergoing mechanical ventilation in the intensive care unit.Br J Anaesth. 1999; 83: 698-701Abstract Full Text PDF PubMed Scopus (45) Google Scholar However, many units still rely on staff assessment of sedation rather than routinely employing any of the available scoring systems. Watling and colleagues34Watling SM Dasta JF Seidl EC Sedatives, analgesics, and paralytics in the ICU.Ann Pharmacother. 1997; 31: 148-153Crossref PubMed Scopus (69) Google Scholar reported that just 26% of the respondents in their survey of ICUs in the USA used a sedation scale, while Christensen and Thunedborg18Christensen BV Thunedborg LP Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs 1996/97. A national survey.Intensive Care Med. 1999; 25: 186-191Crossref PubMed Scopus (75) Google Scholar 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 scale45Ramsay MAE Savage TM Simpson BRJ Goodwin R Controlled sedation with alphaxalone–alphadolone.Br Med J. 1974; ii: 656-659Crossref Scopus (2239) Google Scholar 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.51Hansen-Flaschen J Cowen J Polomano RC Beyond the Ramsay scale: need for a validated measure of sedating drug efficacy in the intensive care unit.Crit Care Med. 1994; 22: 732-733Crossref PubMed Scopus (159) Google Scholar 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.52Brook AD Ahrens TS Schaiff R et al.Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation.Crit Care Med. 1999; 27: 2609-2615Crossref PubMed Scopus (809) Google Scholar
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