title: Safety and efficacy of dexmedetomidine for long-term sedation in critically ill patients.
abstract: OBJECTIVE
  We evaluated the safety and efficacy of long-term administration of dexmedetomidine in patients in the intensive care unit (ICU). Primary endpoint was the incidence of hypotension, hypertension, and bradycardia. Secondary endpoints were withdrawal symptoms, rebound effects, the duration of sedation with Richmond Agitation-Sedation Scale (RASS) ≤ 0 relative to the total infusion time of dexmedetomidine, and the dose of additional sedatives or analgesics.
  
  
  METHODS
  Dexmedetomidine 0.2-0.7 μg/kg/h was continuously infused for maintaining RASS ≤ 0 in patients requiring sedation in the ICU. Safety and efficacy of short-term (≤ 24 h) and long-term (>24 h) dexmedetomidine administration were compared.
  
  
  RESULTS
  Seventy-five surgical and medical ICU patients were administered dexmedetomidine. The incidence of hypotension, hypertension, and bradycardia that occurred after 24 h (long-term) was not significantly different from that occurring within 24 h (short-term) (P = 0.546, 0.513, and 0.486, respectively). Regarding withdrawal symptoms, one event each of hypertension and headache occurred after the end of infusion, but both were mild in severity. Increases of mean arterial blood pressure and heart rate after terminating the infusion of dexmedetomidine were not associated with the increasing duration of its infusion. The ratio of duration with RASS ≤ 0 was ≥ 85 % until day 20, except day 9 (70 %) and day 10 (75 %). There was no increase in the dose of additional sedatives or analgesics after the first 24-h treatment period.
  
  
  CONCLUSIONS
  Long-term safety of dexmedetomidine compared to its use for 24 h was confirmed. Dexmedetomidine was useful to maintain an adequate sedation level (RASS ≤ 0) during long-term infusion.
authors.affiliation: Department of Anesthesiology, Tokyo Women's Medical University Hospital, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozaki
authors.forename: Junzo
authors.initials: J
authors.lastname: Takeda
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shiokawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Matsuyuki
authors.initials: M
authors.lastname: Doi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kakihana
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fujino
authors.forename: Masanori
authors.initials: M
authors.lastname: Takinami
authors.forename: Misa
authors.initials: M
authors.lastname: Kawai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use*; D016638:Critical Illness; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D007022:Hypotension / Q000453:epidemiology; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000700:Analgesics; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine
references.citation: Respir Med. 2011 Aug;105(8):1109-17
references.pmid: 21354774
references.citation: Am J Respir Crit Care Med. 1999 Jun;159(6):1742-6
references.pmid: 10351912
references.citation: Crit Care Med. 1998 May;26(5):947-56
references.pmid: 9590327
references.citation: Anesth Analg. 2000 Mar;90(3):699-705
references.pmid: 10702460
references.citation: Anesthesiology. 2000 Nov;93(5):1345-9
references.pmid: 11046225
references.citation: Curr Opin Crit Care. 2008 Aug;14(4):403-7
references.pmid: 18614903
references.citation: Pharmacotherapy. 2005 May;25(5 Pt 2):8S-18S
references.pmid: 15899744
references.citation: Anesthesiology. 2002 Apr;96(4):1004-17
references.pmid: 11964611
references.citation: Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44
references.pmid: 12421743
references.citation: Crit Care Med. 2001 Mar;29(3):573-80
references.pmid: 11373423
references.citation: Anaesthesia. 1987 Jun;42(6):619-26
references.pmid: 3618995
references.citation: Crit Care Med. 2013 Jan;41(1):263-306
references.pmid: 23269131
references.citation: Postgrad Med. 2002 Feb;111(2):59-60, 63-4, 67-70 passim
references.pmid: 11868314
references.citation: Crit Care Nurs Clin North Am. 2005 Sep;17(3):211-23
references.pmid: 16115529
references.citation: Chest. 1993 Feb;103(2):557-64
references.pmid: 8432154
references.citation: Anesthesiology. 2000 Aug;93(2):382-94
references.pmid: 10910487
references.citation: Curr Drug Saf. 2010 Jan;5(1):6-12
references.pmid: 20210713
references.citation: Anesth Analg. 2008 Jul;107(1):167-70
references.pmid: 18635484
references.citation: Stat Med. 2010 Dec 30;29(30):3186-93
references.pmid: 21170912
references.citation: Psychosomatics. 2009 May-Jun;50(3):206-17
references.pmid: 19567759
references.citation: Anesthesiology. 2004 Nov;101(5):1066-76
references.pmid: 15505441
references.citation: JAMA. 2009 Feb 4;301(5):489-99
references.pmid: 19188334
references.citation: Crit Care Med. 2001 Jul;29(7):1370-9
references.pmid: 11445689
references.citation: J Anesth. 2009;23(1):147-50
references.pmid: 19234843
references.citation: JAMA. 2012 Mar 21;307(11):1151-60
references.pmid: 22436955
references.citation: Intensive Care Med. 2004 Dec;30(12):2188-96
references.pmid: 15338124