Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation
Esko Ruokonen| Ilkka Parviainen| Stephan M. Jakob| Silvia Nunes| Maija Kaukonen| Stephen T. Shepherd| Toni Sarapohja| J. Raymond Bratty| Jukka Takala
Pages 282 - 290
To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay.
A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n = 85) within the first 72 h of ICU stay with an expected ICU stay of ≥48 h and sedation need for ≥24 h after randomization. Patients were assigned to either DEX (≤1.4 μg kg−1 h−1; n = 41) or SC (n = 44), with daily sedation stops.
Non-inferiority of DEX versus SC was not confirmed. Target Richmond agitation–sedation score (RASS) was reached a median of 64% (DEX) and 63% (SC) of the sedation time (ns). The length of ICU stay was similar in DEX and SC. Patients with RASS target 0–3 (DEX 78%, SC 80%) were at target sedation 74% (DEX) and 64% (SC) of the time (ns), whereas those with RASS target −4 or less reached the target 42% (DEX) and 62% (SC) of the time (P = .006). Post hoc analyses suggested shorter duration of mechanical ventilation for DEX (P = 0.025).
This pilot study suggests that in long-term sedation, DEX is comparable to SC in maintaining sedation targets of RASS 0 to −3 but not suitable for deep sedation (RASS −4 or less). DEX had no effect on length of ICU stay. Its effects on other relevant clinical outcomes, such as duration of mechanical ventilation, should be tested further.
- Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, Kollef MH (1999) Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med 27:2609–2615
- Kress JP, Pohlman AS, O’Connor MF, Hall JB (2000) Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 342:1471–1477
- Sydow M, Neumann P (1999) Sedation for the critically ill. Intensive Care Med 25:634–636
- Virtanen R, Savola JM, Saano V, Nyman L (1988) Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol 150:9–14
- Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ (2000) Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 90:699–705
- Venn RM, Grounds RM (2001) Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth 87:684–690
- Venn RM, Hell J, Grounds RM (2000) Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care 4:302–308
- Bloor BC, Ward DS, Belleville JP, Maze M (1992) Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 77:1134–1142
- Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD (2000) The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 93:382–394
- Herr DL, Sum-Ping ST, England M (2003) ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens. J Cardiothorac Vasc Anesth 17:576–584
- Corbett SM, Rebuck JA, Greene CM, Callas PW, Neale BW, Healey MA, Leavitt BJ (2005) Dexmedetomidine does not improve patient satisfaction when compared with propofol during mechanical ventilation. Crit Care Med 33:940–945
- Shehabi Y, Ruettimann U, Adamson H, Innes R, Ickeringill M (2004) Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects. Intensive Care Med 30:2188–2196
- Venn M, Newman J, Grounds M (2003) A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med 29:201–207
- Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW (2007) Effect of sedation with dexmedetomidine vs. lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 298:2644–2653
- Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O’Neal PV, Keane KA, Tesoro EP, Elswick RK (2002) The Richmond Agitation–Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 166:1338–1344
- Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 22:707–710
- Bennett-Guerrero E, Welsby I, Dunn TJ, Young LR, Wahl TA, Diers TL, Phillips-Bute BG, Newman MF, Mythen MG (1999) The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery. Anesth Analg 89:514–519
- Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R (2001) Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU. JAMA 286:2703–2710
- MacLaren R, Forrest LK, Kiser TH (2007) Adjunctive dexmedetomidine therapy in the intensive care unit: a retrospective assessment of impact on sedative and analgesic requirements, levels of sedation and analgesia, and ventilatory and hemodynamic parameters. Pharmacotherapy 27:351–359
- Siobal MS, Kallet RH, Kivett VA, Tang JF (2006) Use of dexmedetomidine to facilitate extubation in surgical intensive-care-unit patients who failed previous weaning attempts following prolonged mechanical ventilation: a pilot study. Respir Care 51:492–496
- Pandharipande P, Ely EW (2005) Narcotic-based sedation regimens for critically ill mechanically ventilated patients. Crit Care 9:247–248
- Mayo-Smith MF (1997) Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA 278:144–151
- Prielipp RC, Wall MH, Tobin JR, Groban L, Cannon MA, Fahey FH, Gage HD, Stump DA, James RL, Bennett J, Butterworth J (2002) Dexmedetomidine-induced sedation in volunteers decreases regional and global cerebral blood flow. Anesth Analg 95:1052–1059