Addition of dexmedetomidine to benzodiazepines for patients with alcohol withdrawal syndrome in the intensive care unit: a randomized controlled study

Kateryna Bielka, Iurii Kuchyn, Felix Glumcher, Kateryna Bielka, Iurii Kuchyn, Felix Glumcher

Abstract

Background: Dexmedetomidine (DEX) is a centrally acting alpha-2-adrenoceptor agonist that has potential in the management of alcohol withdrawal syndrome (AWS) owing to its ability to produce arousable sedation and to inhibit the adrenergic system without respiratory depression. The objective of this randomized controlled study was to evaluate whether addition of DEX to benzodiazepine (BZD) therapy is effective and safe for AWS patients in the intensive care unit (ICU).

Methods: Eligible participants were randomly assigned to intervention (Group D; n = 36) or control (Group C; n = 36). In Group D, DEX infusion was started at a dose of 0.2-1.4 μg/kg/h and titrated to achieve the target sedation level (-2 to 0 on the Richmond Agitation Sedation Scale (RASS)) with symptom-triggered BZD (10 mg diazepam bolus) was used as needed. Patients in Group C received only symptom-triggered 10 mg boluses of diazepam. The primary efficacy outcomes were 24-h diazepam consumption and cumulative diazepam dose required over the course of the ICU stay; secondary outcomes included length of ICU stay, sedation and communication quality and haloperidol requirements.

Results: Median 24-h diazepam consumption during the study was significantly lower in Group D (20 vs. 40 mg, p < 0.001), as well as median cumulative diazepam dose during the ICU stay (60 vs. 90 mg, p < 0.001). The median percentage of time in the target sedation range was higher in Group D (median 90 % (90-95) vs. 64.5 % (60-72.5; p < 0.001). DEX infusion was also associated with better nurse-assessed patient communication (<0.001) and fewer patients requiring haloperidol treatment (2 vs. 10 p = 0.02). One patient in Group D and four in Group C were excluded owing to insufficient control of AWS symptoms and use of additional sedatives (p = 0.36). There were no severe adverse events in either group. Spontaneous breathing remained normal in all patients. Bradycardia was a common adverse event in Group D (10 vs. 2; p = 0.03).

Conclusions: DEX significantly reduced diazepam requirements in ICU patients with AWS and decreased the number of patients who required haloperidol for severe agitation and hallucinations. DEX use was also associated with improvement in diverse aspects of sedation quality and the quality of patient communication.

Trial registration: ClinicalTrials.gov: NCT02496650.

Keywords: Alcohol withdrawal syndrome; Benzodiazepines; Dexmedetomidine; Randomized controlled trial; Sedation.

Figures

Fig. 1
Fig. 1
CONSORT flowchart
Fig. 2
Fig. 2
Diazepam 24-h consumption and cumulative dose during ICU stay

References

    1. Rayner SG, Weinert CR, Peng H, Jepsen S, Broccard AF. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 2012;2(1):12. doi: 10.1186/2110-5820-2-12.
    1. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010;17(3):CD005063.
    1. Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium. An evidence-based practice guideline. Arch Intern Med. 2004;164(13):1405–1412. doi: 10.1001/archinte.164.13.1405.
    1. Al-Sanouri I, Dikin M, Soubani AO. Critical care aspects of alcohol abuse. South Med J. 2005;98(3):372–381. doi: 10.1097/01.SMJ.0000154769.33508.20.
    1. Peppers MP. Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease. Pharmacotherapy. 1996;16(1):49–57.
    1. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the Intensive Care Unit: executive summary. Am J Health Syst Pharm. 2013;70(1):53–58.
    1. Sarff M, Gold JA. Alcohol withdrawal syndromes in the intensive care unit. Crit Care Med. 2010;38(9 Suppl):S494–S501. doi: 10.1097/CCM.0b013e3181ec5412.
    1. Awissi DK, Lebrun G, Coursin DB, Riker RR, Skrobik Y. Alcohol withdrawal and delirium tremens in the critically ill: a systematic review and commentary. Intensive Care Med. 2013;39(1):16–30. doi: 10.1007/s00134-012-2758-y.
    1. Baumgartner GR, Rowen RC. Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial. South Med J. 1991;84(3):312–321. doi: 10.1097/00007611-199103000-00006.
    1. Adinoff B. Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings. Alcohol Clin Exp Res. 1994;18(4):873–878. doi: 10.1111/j.1530-0277.1994.tb00053.x.
    1. Spies CD, Dubisz N, Neumann T, et al. Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial. Crit Care Med. 1996;24(3):414–422. doi: 10.1097/00003246-199603000-00009.
    1. Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009;43(12):2064–2074. doi: 10.1345/aph.1M310.
    1. Muzyk AJ, Fowler JA, Norwood DK, Chilipko A. Role of alpha2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 2011;45(5):649–657. doi: 10.1345/aph.1P575.
    1. Rovasalo A, Tohmo H, Aantaa R, Kettunen E, Palojoki R. Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a case report. Gen Hosp Psychiatry. 2006;28(4):362–363. doi: 10.1016/j.genhosppsych.2006.03.002.
    1. DeMuro JP, Botros DG, Wirkowski E, Hanna AF. Use of dexmedetomidine for the treatment of alcohol withdrawal syndrome in critically ill patients: a retrospective case series. J Anesth. 2012;26:601–605. doi: 10.1007/s00540-012-1381-y.
    1. Tolonen J, Rossinen J, Alho H, Harjola VP. Dexmedetomidine in addition to benzodiazepine-based sedation in patients with alcohol withdrawal delirium. Eur J Emerg Med. 2013;20:425–427. doi: 10.1097/MEJ.0b013e32835c53b3.
    1. Mueller SW, Preslaski CR, Kiser TH, Fish DN, Lavelle JC, Malkowski SP, et al. A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014;42:1131–1139. doi: 10.1097/CCM.0000000000000141.
    1. Moss HB, Chen CM, Yi HY. DSM-IV criteria endorsement patterns in alcohol dependence: relationship to severity. Alcohol Clin Exp Res. 2008;32:306–313. doi: 10.1111/j.1530-0277.2007.00582.x.
    1. : True Random Number service. . Accessed 15 Jan 2013.
    1. Lizotte RJ, Kappes JA, Bartel BJ, Hayes KM, Lesselyoung VL. Evaluating the effects of dexmedetomidine compared to propofol as adjunctive therapy in patients with alcohol withdrawal. Clin Pharmacol. 2014;6:171–177.
    1. Dailey RW, Leatherman JW, Sprenkle MD. Dexmedetomidine in the management of alcohol withdrawal and alcohol withdrawal delirium. Am J Respir Crit Care Med. 2011;183:A3164.

Source: PubMed

3
Sottoscrivi