Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients.

RATIONALE Mechanically ventilated intensive care unit (ICU) patients are frequently managed using a continuous-infusion sedative. Although recent guidelines suggest avoiding benzodiazepines for sedation, this class of drugs is still widely used. There are limited data comparing sedative agents in terms of clinical outcomes in an ICU setting. OBJECTIVES Comparison of propofol to midazolam and lorazepam in adult ICU patients. METHODS Data were obtained from a multicenter ICU database (2003-2009). Patient selection criteria included age greater than or equal to 18 years, single ICU admission with single ventilation event (>48 h), and treatment with continuously infused sedation (propofol, midazolam, or lorazepam). Propensity score analysis (1:1) was used and mortality measured. Cumulative incidence and competing risk methodology were used to examine time to ICU discharge and ventilator removal. MEASUREMENTS AND MAIN RESULTS There were 2,250 propofol-midazolam and 1,054 propofol-lorazepam matched patients. Hospital mortality was statistically lower in propofol-treated patients as compared with midazolam- or lorazepam-treated patients (risk ratio, 0.76; 95% confidence interval [CI], 0.69-0.82 and risk ratio, 0.78; 95% CI, 0.68-0.89, respectively). Competing risk analysis for 28-day ICU time period showed that propofol-treated patients had a statistically higher probability for ICU discharge (78.9% vs. 69.5%; 79.2% vs. 71.9%; P < 0.001) and earlier removal from the ventilator (84.4% vs. 75.1%; 84.3% vs. 78.8%; P < 0.001) when compared with midazolam- and lorazepam-treated patients, respectively. CONCLUSIONS In this large, propensity-matched ICU population, patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of mechanical ventilation.

[1]  Jesse B. Hall,et al.  Rapidly reversible, sedation-related delirium versus persistent delirium in the intensive care unit. , 2014, American journal of respiratory and critical care medicine.

[2]  G. Bernard,et al.  Long-term cognitive impairment after critical illness. , 2013, The New England journal of medicine.

[3]  R. Jaeschke,et al.  Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit , 2013, Critical care medicine.

[4]  D. Roberts,et al.  Sedation for Critically Ill or Injured Adults in the Intensive Care Unit , 2012, Drugs.

[5]  G. Brophy,et al.  Perceived Versus Actual Sedation Practices in Adult Intensive Care Unit Patients Receiving Mechanical Ventilation , 2012, The Annals of pharmacotherapy.

[6]  E. Ely,et al.  Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients* , 2010, Critical care medicine.

[7]  G. Bernard,et al.  Delirium as a predictor of long-term cognitive impairment in survivors of critical illness , 2010, Critical care medicine.

[8]  Torben Martinussen,et al.  A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial , 2010, The Lancet.

[9]  J. Dasta,et al.  An Updated Focused Review of Dexmedetomidine in Adults , 2009, The Annals of pharmacotherapy.

[10]  S. Greenfield,et al.  Comparative Effectiveness Research: A Report From the Institute of Medicine , 2009, Annals of Internal Medicine.

[11]  Bryan R Luce,et al.  Rethinking Randomized Clinical Trials for Comparative Effectiveness Research: The Need for Transformational Change , 2009, Annals of Internal Medicine.

[12]  A Simon Pickard,et al.  Comparative effectiveness research: Relevance and applications to pharmacy. , 2009, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[13]  J. Devlin,et al.  Perceived barriers to the use of sedation protocols and daily sedation interruption: a multidisciplinary survey. , 2009, Journal of critical care.

[14]  G. Bernard,et al.  Delirium and sedation in the intensive care unit: Survey of behaviors and attitudes of 1384 healthcare professionals* , 2009, Critical care medicine.

[15]  E. Ely,et al.  Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. , 2009, JAMA.

[16]  H. Wunsch,et al.  A new era for sedation in ICU patients. , 2009, JAMA.

[17]  A. MacLullich,et al.  Delirium and long-term cognitive impairment , 2009, International review of psychiatry.

[18]  T. Murphy,et al.  Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population* , 2009, Critical care medicine.

[19]  A. Morandi,et al.  Delirium in the intensive care unit , 2009, International review of psychiatry.

[20]  P. Halpern,et al.  Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison , 1997, Intensive Care Medicine.

[21]  J. Maldonado Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment. , 2008, Critical care clinics.

[22]  J. Tebbs,et al.  An Introduction to Categorical Data Analysis , 2008 .

[23]  K. Ho,et al.  The use of propofol for medium and long-term sedation in critically ill adult patients: a meta-analysis , 2008, Intensive Care Medicine.

[24]  P. Pandharipande,et al.  Delirium in the intensive care unit , 2008, Critical care.

[25]  Russell R. Miller,et al.  Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. , 2007, JAMA.

[26]  C. Spies,et al.  Changes in sedation management in German intensive care units between 2002 and 2006: a national follow-up survey , 2007, Critical care.

[27]  B. Pun,et al.  The sedation of critically ill adults: part 2: management. , 2007, The American journal of nursing.

[28]  B. Pun,et al.  The sedation of critically ill adults: Part 1: Assessment. The first in a two-part series focuses on assessing sedated patients in the ICU. , 2007, The American journal of nursing.

[29]  Karen Sakakeeny-Zaal Pediatric Orthopnea and Total Airway Obstruction , 2007 .

[30]  J. Payen,et al.  Current Practices in Sedation and Analgesia for Mechanically Ventilated Critically Ill Patients: A Prospective Multicenter Patient-based Study , 2007, Anesthesiology.

[31]  Russell R. Miller,et al.  Delirium and cognitive dysfunction in the intensive care unit , 2006, Current psychiatry reports.

[32]  Jesse B. Hall,et al.  Sedation in the mechanically ventilated patient , 2006, Critical care medicine.

[33]  Jesse B. Hall,et al.  A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients* , 2006, Critical care medicine.

[34]  Sangeeta Mehta,et al.  Canadian survey of the use of sedatives, analgesics, and neuromuscular blocking agents in critically ill patients* , 2006, Critical care medicine.

[35]  G. Bernard,et al.  Lorazepam Is an Independent Risk Factor for Transitioning to Delirium in Intensive Care Unit Patients , 2006, Anesthesiology.

[36]  P. Pandharipande,et al.  Delirium: acute cognitive dysfunction in the critically ill , 2005, Current opinion in critical care.

[37]  Theodore Speroff,et al.  Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. , 2004, JAMA.

[38]  G. Bernard,et al.  Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: A survey of 912 healthcare professionals* , 2004, Critical care medicine.

[39]  D. Rhoney,et al.  National Survey of the Use of Sedating Drugs, Neuromuscular Blocking Agents, and Reversal Agents in the Intensive Care Unit , 2003, Journal of intensive care medicine.

[40]  S. Cook,et al.  Project IMPACT: Results from a Pilot Validity Study of a New Observational Database , 2002, Critical care medicine.

[41]  Philip D Lumb,et al.  Sedation, analgesia, and neuromuscular blockade of the critically ill adult: revised clinical practice guidelines for 2002. , 2002, Critical care medicine.

[42]  Philip D Lumb,et al.  Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. , 2002, Critical care medicine.

[43]  G. Bernard,et al.  Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). , 2001, JAMA.

[44]  J. Magarey Propofol or midazolam--which is best for the sedation of adult ventilated patients in intensive care units? A systematic review. , 2001, Australian critical care : official journal of the Confederation of Australian Critical Care Nurses.

[45]  J. Rello,et al.  International Conference for the Development of Consensus on the Diagnosis and Treatment of Ventilator-associated Pneumonia. , 2001, Chest.

[46]  Theodore Speroff,et al.  Evaluation of delirium in critically ill patients: Validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) , 2001, Critical care medicine.

[47]  D. Moher,et al.  Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial. , 2001, Chest.

[48]  S. Inouye,et al.  Delirium in the Intensive Care Unit: An Under-Recognized Syndrome of Organ Dysfunction , 2001, Seminars in respiratory and critical care medicine.

[49]  G. Biggio,et al.  Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. , 2000, Current medicinal chemistry.

[50]  E. Alted-López,et al.  Propofol Versus Midazolam: Safety and Efficacy for Sedating the Severe Trauma Patient , 1998, Anesthesia and analgesia.

[51]  R. Barrientos-Vega,et al.  Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. , 1997, Critical care medicine.

[52]  M. Barrios,et al.  Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial. , 1996, Critical care medicine.

[53]  S. Nasraway,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. , 1995, Critical care medicine.

[54]  R. Levine Pharmacology of intravenous sedatives and opioids in critically ill patients. , 1994, Critical care clinics.

[55]  G. Carrasco,et al.  Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost-benefit analysis. , 1993, Chest.

[56]  A. Agresti An introduction to categorical data analysis , 1997 .

[57]  E. Gepts,et al.  Pharmacokinetic Implications for the Clinical Use of Propofol , 1989, Clinical pharmacokinetics.

[58]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .