Log in | Register

Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis

Jen A. Tan| Kwok M. Ho
Review
Volume 36, Issue 6 / June , 2010

Pages 926 - 939

Abstract

Purpose

To assess the effects of using dexmedetomidine as a sedative and analgesic agent on length of intensive care unit (ICU) stay, duration of mechanical ventilation, risk of bradycardia, and hypotension in critically ill adult patients.

Methods

Two researchers searched MEDLINE, EMBASE, and the Cochrane controlled trial register independently for randomized controlled trials comparing dexmedetomidine with a placebo or an alternative sedative agent, without any language restrictions.

Results

A total of 2,419 critically ill patients from 24 trials were subject to meta-analysis. Dexmedetomidine was associated with a significant reduction in length of ICU stay [weighted mean difference −0.48 days, 95% confidence interval (CI) −0.18 to −0.78 days, P = 0.002], but not duration of mechanical ventilation, when compared with an alternative sedative agent. There was, however, significant heterogeneity in these two outcomes between the pooled studies. Dexmedetomidine was associated with increased risk of bradycardia requiring interventions in studies that used both a loading dose and maintenance doses >0.7 μg kg−1 h−1 [relative risk (RR) 7.30, 95% CI 1.73–30.81, P = 0.007]. Risks of hypotension requiring interventions (RR 1.43, 95% CI 0.78–2.6, P = 0.25), delirium (RR 0.79, 95% CI 0.56–1.11, P = 0.18), self-extubation, myocardial infarction, hyperglycemia, atrial fibrillation, and mortality were not significantly different between dexmedetomidine and traditional sedative and analgesic agents.

Conclusions

Significant heterogeneity existed between the pooled studies. The limited evidence suggested that dexmedetomidine might reduce length of ICU stay in some critically ill patients, but the risk of bradycardia was significantly higher when both a loading dose and high maintenance doses (>0.7 μg kg−1 h−1) were used.

Keywords

References

  1. Gravel NR, Searle NR, Sahab PG, Carrier M (1999) Sedation in critically ill patients: practical recommendation. CNS Drugs 11:9–22
    • View reference on publisher's website
  2. Ho KM, Ng JY (2008) The use of propofol for medium and long-term sedation in critically ill adult patients: a meta-analysis. Intensive Care Med 34:1969–1979
  3. Riker RR, Fraser GL (2009) Altering intensive care sedation paradigms to improve patient outcomes. Crit Care Clin 25:527–538
    • View reference on publisher's website
    • View reference on PubMed
  4. Tan JA, Ho KM (2009) Use of remifentanil as a sedative agent in critically ill adult patients: a meta-analysis. Anaesthesia 64:1342–1352
    • View reference on publisher's website
    • View reference on PubMed
  5. Paris A, Tonner PH (2005) Dexmedetomidine in anaesthesia. Curr Opin Anaesthesiol 18:412–418
    • View reference on publisher's website
    • View reference on PubMed
  6. Guo TZ, Jiang JY, Buttermann AE, Maze M (1996) Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology 84:873–881
    • View reference on publisher's website
    • View reference on PubMed
  7. Venn RM, Hell J, Grounds RM (2000) Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care 4:302–308
    • View reference on publisher's website
    • View reference on PubMed
  8. Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, Vedio A, Singer M, Feneck R, Treacher D, Willatts SM, Grounds RM (1999) Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 54:1136–1142
    • View reference on publisher's website
    • View reference on PubMed
  9. Huupponen E, Maksimow A, Lapinlampi P, Särkelä M, Saastamoinen A, Snapir A, Scheinin H, Scheinin M, Meriläinen P, Himanen SL, Jääskeläinen S (2008) Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol Scand 52:289–294
    • View reference on publisher's website
    • View reference on PubMed
  10. Sichrovsky TC, Mittal S, Steinberg JS (2008) Dexmedetomidine sedation leading to refractory cardiogenic shock. Anesth Analg 106:1784–1786
    • View reference on publisher's website
    • View reference on PubMed
  11. Venn RM, Karol MD, Grounds RM (2002) Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care. Br J Anaesth 88:669–675
    • View reference on publisher's website
    • View reference on PubMed
  12. Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219
    • View reference on publisher's website
    • View reference on PubMed
  13. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560
    • View reference on publisher's website
    • View reference on PubMed
  14. Wahlander S, Frumento RJ, Wagener G, Saldana-Ferretti B, Joshi RR, Playford HR, Sladen RN (2005) A prospective, double-blind, randomized, placebo-controlled study of dexmedetomidine as an adjunct to epidural analgesia after thoracic surgery. J Cardiothorac Vasc Anesth 19:630–635
    • View reference on publisher's website
    • View reference on PubMed
  15. Akin S, Aribogan A, Arslan G (2008) Dexmedetomidine as an adjunct to epidural analgesia after abdominal surgery in elderly intensive care patients: a prospective, double-blind, clinical trial. Curr Ther Res Clin Exp 69:16–28
    • View reference on publisher's website
  16. Kaneko T (2008) Postoperative management of carotid endarterectomy with dexmedetomidine—a comparison with propofol. Masui 57:696–703
    • View reference on PubMed
  17. Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J (2009) Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology 111:1075–1084
    • View reference on publisher's website
    • View reference on PubMed
  18. Triltsch AE, Welte M, von Homeyer P, Grosse J, Genähr A, Moshirzadeh M, Sidiropoulos A, Konertz W, Kox WJ, Spies CD (2002) Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebo-controlled phase II study. Crit Care Med 30:1007–1014
    • View reference on publisher's website
    • View reference on PubMed
  19. 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
    • View reference on publisher's website
    • View reference on PubMed
  20. Martin E, Ramsay G, Mantz J, Sum-Ping ST (2003) The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med 18:29–41
    • View reference on publisher's website
    • View reference on PubMed
  21. Memiş D, Hekimoğlu S, Vatan I, Yandim T, Yüksel M, Süt N (2007) Effects of midazolam and dexmedetomidine on inflammatory responses and gastric intramucosal pH to sepsis, in critically ill patients. Br J Anaesth 98:550–552
    • View reference on publisher's website
    • View reference on PubMed
  22. Memiş D, Dökmeci D, Karamanlioğlu B, Turan A, Türe M (2006) A comparison of the effect on gastric emptying of propofol or dexmedetomidine in critically ill patients: preliminary study. Eur J Anaesthesiol 23:700–704
    • View reference on publisher's website
    • View reference on PubMed
  23. 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
    • View reference on publisher's website
    • View reference on PubMed
  24. Elbaradie S, El Mahalawy FH, Solyman AH (2004) Dexmedetomidine vs. propofol for short-term sedation of postoperative mechanically ventilated patients. J Egypt Natl Cancer Inst 16:153–158
  25. Ruokonen E, Parviainen I, Jakob SM, Nunes S, Kaukonen M, Shepherd ST, Sarapohja T, Bratty JR, Takala J, “Dexmedetomidine for Continuous Sedation” Investigators (2009) Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med 35:282–290
  26. Memiş D, Kargi M, Sut N (2009) Effects of propofol and dexmedetomidine on indocyanine green elimination assessed with LIMON to patients with early septic shock: a pilot study. J Crit Care 24:603–608
    • View reference on publisher's website
    • View reference on PubMed
  27. Tasdogan M, Memis D, Sut N, Yuksel M (2009) Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis. J Clin Anesth 21:394–400
    • View reference on publisher's website
    • View reference on PubMed
  28. Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, Mangano DT (1995) Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The study of perioperative ischemia research group. Anesthesiology 82:620–633
    • View reference on PubMed
  29. Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, Heard S, Cheung A, Son SL, Kallio A (2000) The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 90:834–839
    • View reference on publisher's website
    • View reference on PubMed
  30. 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
    • View reference on publisher's website
    • View reference on PubMed
  31. Reade MC, O’Sullivan K, Bates S, Goldsmith D, Ainslie WR, Bellomo R (2009) Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit Care 13:R75
    • View reference on publisher's website
    • View reference on PubMed
  32. Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA (2009) Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics 50:206–217
    • View reference on publisher's website
    • View reference on PubMed
  33. Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG, SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group (2009) Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 301:489–499
    • View reference on publisher's website
    • View reference on PubMed
  34. 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
    • View reference on publisher's website
    • View reference on PubMed
  35. Ozkan N, Sahin N, Karakaya Kabukcu H, Celikbilek G, Aydogdu Titiz T (2007) Comparison of the effects of dexmedetomidine with midasolam on haemodynamics and oxygen profile in patients undergoing coronary artery bypass grafting. Gogus-Kalp-Damar Anestezi ve Yogun Bakim Dernegi Dergisi 13:161–168
  36. Esmaoglu A, Ulgey A, Akin A, Boyaci A (2009) Comparison between dexmedetomidine and midazolam for sedation of eclampsia patients in the intensive care unit. J Crit Care 24:551–555
    • View reference on publisher's website
    • View reference on PubMed
  37. Dasta JF, Kane-Gill SL, Pencina M, Shehabi Y, Bokesch PM, Wisemandle W, Riker RR (2010) A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit. Crit Care Med 38:497–503
    • View reference on publisher's website
    • View reference on PubMed
  38. 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
    • View reference on publisher's website
    • View reference on PubMed
  39. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW (2008) Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (awakening and breathing controlled trial): a randomised controlled trial. Lancet 371:126–134
    • View reference on publisher's website
    • View reference on PubMed
  40. Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, Spears L, Miller M, Franczyk M, Deprizio D, Schmidt GA, Bowman A, Barr R, McCallister KE, Hall JB, Kress JP (2009) Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 373:1874–1882
    • View reference on publisher's website
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement