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CASE REPORT
Year : 2019  |  Volume : 28  |  Issue : 2  |  Page : 321-324  Table of Contents     

Adjunctive dexmedetomidine for treatment of delirium tremens: Case report and brief review


1 Department of Psychiatry, Command Hospital (Southern Command), Pune, Maharashtra, India
2 Department of Anaesthesia, AFMC, Pune, Maharashtra, India

Date of Submission18-Jun-2020
Date of Acceptance03-Jul-2020
Date of Web Publication14-Aug-2020

Correspondence Address:
Dr. Amresh Dubey
Department of Psychiatry, Command Hospital, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ipj.ipj_118_20

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   Abstract 


Alcohol withdrawal delirium (delirium tremens [DT]) is a medical emergency. Gamma-aminobutyric acid type A agonists (benzodiazepines [BZDs]) are the mainstay of treatment. Resistant alcohol withdrawal requires adjunctive medications along with BZDs and supportive care. DT is associated with significant autonomic dysfunction (sympathetic hyperactivity). Dexmedetomidine is a selective a2-adrenergic receptor agonist which reduces sympathetic over-activity and agitation in delirious patients. We present a case of alcohol withdrawal delirium (DT) who responded well to adjunctive dexmedetomidine infusion resulting in reduced sympathetic activity and reduced dose requirement of BZDs.

Keywords: Alcohol withdrawal state, alpha-2 agonist, delirium tremens, dexmedetomidine, resistant alcohol withdrawal


How to cite this article:
Chail A, Dubey A, Singh YM, Jahan N. Adjunctive dexmedetomidine for treatment of delirium tremens: Case report and brief review. Ind Psychiatry J 2019;28:321-4

How to cite this URL:
Chail A, Dubey A, Singh YM, Jahan N. Adjunctive dexmedetomidine for treatment of delirium tremens: Case report and brief review. Ind Psychiatry J [serial online] 2019 [cited 2020 Oct 24];28:321-4. Available from: https://www.industrialpsychiatry.org/text.asp?2019/28/2/321/291964



Alcohol use disorders represent a major public health problem with a reported prevalence of around 4.6%.[1] Alcohol withdrawal delirium (delirium tremens [DT]) is a medical emergency which occurs in 5% of individuals with alcohol dependence and occurs 2–5 days after sudden reduction or stoppage of alcohol consumption. It has a mortality rate of 20%–50% without treatment and 5%–10% with treatment.[2]

Rating scales used for the assessment of symptoms severity in DT include Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar)[3] and Richmond Agitation-Sedation Scale (RASS).[4] Benzodiazepines (BDZ) are the first line of treatment in alcohol withdrawal state. Some patients require >40 mg of diazepam or equivalent in 1 h for the management for AWS which is also known as resistant alcohol withdrawal (RAW).[5] There is evidence that in such patients use of dexmedetomidine in addition to BZDs led to the decrease in severity of alcohol withdrawal, reduction in sympathetic hyperactivity and reduced dose requirement of BZDs.[6],[7],[8] We present a case of severe alcohol withdrawal that had poor response to high doses of BZDs, but had rapid improvement to adjunctive dexmedetomidine infusion.


   Case Report Top


A 32-year-old male with a history of severe alcohol dependence was referred to our hospital for management of alcohol withdrawal from a peripheral centre. He had a history of multiple hospitalizations and relapses in the last 2 years. In the current episode, he developed generalized tremulousness, nausea and excessive sweating, within a day of stoppage of regular heavy drinking. He had two Generalised Tonic-Clonic Seizures (GTCS) on the same day which led to his hospitalisation in the peripheral centre.

On initial evaluation at 0800 h Day 1, he was disoriented to time place and person. He had tachycardia (heart rate [HR]: 120/min), raised blood pressure (BP) (150/100 mmHg), generalized tremulousness, and profuse sweating. He was restless, uncooperative, and agitated.

His hematological and biochemical investigations showed mean corpuscular volume of 101 fL and hypokalemia and hypomagnesemia with serum potassium level of 2.8 mEq/L and serum magnesium of 1.3 mg/dl, respectively. His noncontrast computed tomography head was essentially normal.

He was diagnosed with a case of alcohol withdrawal delirium. His initial CIWA-ar score was 29. He was given 08 mg of injection lorazepam over 01 h. He had minimal symptom control with the same. A total of 36 mg lorazepam was given on D1. He was also given, tab Haloperidol 5 mg orally and injection haloperidol 5 mg I/M, adequate hydration, electrolytes and injection Thiamine 1000 mg/day. In view of hypokalaemia and hypomagnesemia, injection Potassium Chloride (KCl) 100 meq/L intravenous (IV) over 24 h, and injection magnesium sulphate 4 g slow IV over 48 h were administered. However despite this, his RASS score varied from + 3 to + 2 and CIWA-Ar was around 14–16.

His BZD was switched to midazolam infusion on D3 and augmented with dexmedetomidine infusion on D4, as shown in [Table 1]. By day 5, individual was oriented and cooperative and his vital parameters stabilized (HR 82/min and BP128/84 mmhg). His oral BZDs were tapered off and tab acamprosate (neuro-protective) (333 mg Thrice a day (TDS)) and naltrexone (50 mg OD) (in view of hedonistic drinking) was started. He was also given benefit of motivational enhancement therapy and cognitive behavioral therapy for relapse prevention. He was subsequently discharged after 4 weeks of inpatient care.
Table: 1 Course in hospital

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Brief review

Dexmedetomidine (an imidazole compound) is the pharmacologically active dextroisomer of medetomidine and a selective α2adrenoceptor agonist. Its dexmedetomidine is 08 times more specific for α2-adrenoceptors than clonidine. The α-2: α-1 specificity of clonidine is 220:1, whereas for dexmedetomidine its 1620:1.[9] The actions of dexmedetomidine are suggested to be mediated through presynaptic α2-adrenoceptors which activate pertussis toxin-sensitive G proteins, thereby increasing conductance through potassium ion channels. It inhibits the release of norepinephrine from synaptic vesicles. This leads to an inhibition of sympathetic activity, thereby leading to sedation and anxiolysis.[10] Healthy individuals treated with dexmedetomidine at low concentrations have been demonstrated to have decreased norepinephrine levels and decreased HRs.[11]

Pharmacokinetics

It has a half-life of 6 min and terminal half-life 2 h. The average protein binding is 94%. Biotransformation involves both direct glucuronidation as well as cytochrome P450-mediated metabolism. 95% is excreted in urine and 4% in feces.[10]

Dosing

As per the US Food and Drug Administration recommended dose of dexmedetomidine for conscious sedation is between 0.2 and 0.7 μg/kg/h.[12] However, doses in the studies varied widely, from 0.2 μg/kg/h up to 4.6 μg/kg/h. In a study by Tolonen et al., patients received very high-infusion rates (>2.7 μg/kg/h) and experienced a high rate of adverse events, including pneumonia, respiratory failure, and the need for noninvasive mechanical ventilation.[13] Taking these outcomes into account, best practice at this time seems to be slow titration with maximum dose individualized based on response and adverse effects.

Adverse effects

Some of the notable adverse effects include bradycardia, sinus arrest, and hypotension.[10]

Clinical benefits of dexmedetomidine versus propofol

Studies indicate that dexmedetomidine may offer advantages over propofol in terms of decrease in the length of intensive care unit (ICU) stay, risk of delirium, and need for mechanical ventilation.[14],[15] Dexmedetomidine reduces the need for BZDs and is a promising and effective adjuvant treatment for AWS.[8]


   Discussion Top


Prolonged alcohol use leads to downregulation of gamma-aminobutyric acid (GABA) receptors and increased expression of NMDA receptors. Abrupt cessation of chronic alcohol consumption unmasks these changes with a glutamate-mediated CNS excitation resulting in autonomic over activity which involves noradrenergic system.[15] BZDs (GABAA agonists) reduce withdrawal symptom severity, duration, risk of delirium, and incidence of seizure.[15] Dose equivalence of BDZ is usually calculated as: 10 mg Diazepam is approximately =1 mg Lorazepam= 2.67 mg Midazolam.[16] Patients with severe or RAW are more likely to require intubation and mechanical ventilation and experience longer ICU and hospital stays.[11] Such cases require treatment augmentation with anesthetic agents (propofol), phenobarbital, or alpha agonists (dexmedetomidine).

Our patient had RAW. Dexmedetomidine was preferred over other options as it is sympatholytic, sedating, and reduces agitation along with reducing the risk of respiratory depression and mechanical ventilation. He had a rapid response in the severity of symptoms and was shifted out of ICU a day after initiation of dexmedetomidine. This highlights the potential efficacy and safety of dexmedetomidine as an adjunct in alcohol withdrawal delirium.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was financially supported by the Department of Psychiatry, Command Hospital, Pune and Department of Anaesthesia, AFMC, Pune, India.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Gururaj G, Varghese M, Benegal V, Rao GN, Pathak K, Singh LK, et al. and NMHS collaborators group. National Mental Health Survey of India, 2015-16: Prevalence, patterns and outcomes. Bengaluru, National Institute of Mental Health and Neuro Sciences, NIMHANS Publication No. 129, 2016. Available from http://indianmhs.nimhans.ac.in/Docs/Report2.pdf [Last accessed on 2020 Apr28].  Back to cited text no. 1
    
2.
Subodh BN, Umamaheswari V. Synopsis of the Clinical Practice Guidelines on management of Alcohol Use Disorders. In: Basu D, Dalal PK (eds). Synopsis of the Clinical Practice Guidelines on Substance Use Disorders. New Delhi: Indian Psychiatric Society; 2015. p. 21-35.  Back to cited text no. 2
    
3.
Taylor DM, Barnes TR, Young AH editors. The Maudsley Prescribing Guidelines in Psychiatry. 13th ed. Hoboken, NJ; Wiley Blackwell; 2018.  Back to cited text no. 3
    
4.
Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, et al. The richmond agitation-sedation scale: Validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002;166:1338-44.  Back to cited text no. 4
    
5.
Hack JB, Hoffmann RS, Nelson LS. Resistant alcohol withdrawal: Does an unexpectedly large sedative requirement identify these patients early? J Med Toxicol 2006;2:55-60.  Back to cited text no. 5
    
6.
Rayner SG, Weinert CR, Peng H, Jepsen S, Broccard AF, Study Institution. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care 2012;2:12.  Back to cited text no. 6
    
7.
Kalabalik J, Sullivan JB. Use of Dexmedetomidine in the Management of Alcohol Withdrawal Syndrome in Critically Ill Patients. Int J Crit Care Emerg Med 2015;1:1-5.  Back to cited text no. 7
    
8.
Muzyk AJ, Kerns S, Brudney S, Gagliardi JP. Dexmedetomidine for the treatment of alcohol withdrawal syndrome: Rationale and current status of research. CNS Drugs 2013;27:913-20.  Back to cited text no. 8
    
9.
Giovannitti Jr JA, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: A review of current clinical applications. Anesth Prog 2015;62:31-9.  Back to cited text no. 9
    
10.
Dexmedetomidine C13H16N2 PubChem. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Dexmedetomidine. [Last accessed on 2020 Jun 14].  Back to cited text no. 10
    
11.
Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000;93:382-94.  Back to cited text no. 11
    
12.
FDA US. Prescribing Information Dexmedetomidine Hydrochloride Injection; 2015. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/ label/2015/206628s000lbl.pdf [Cited on 2020 April 30].  Back to cited text no. 12
    
13.
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;20:425-7.  Back to cited text no. 13
    
14.
Wong A, Benedict NJ, Kane-Gill SL. Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal. J Crit Care 2015;30:405-9.  Back to cited text no. 14
    
15.
Jesse S, Bråthen G, Ferrara M, Keindl M, Ben-Menachem E, Tanasescu R, et al. Alcohol withdrawal syndrome: Mechanisms, manifestations, and management. Acta Neurol Scand 2017;135:4-16.  Back to cited text no. 15
    
16.
Benzodiazepine Equivalents Conversion Calculator. Available from: https://clincalc.com/Benzodiazepine/default.aspx. [Last accessed on 2020 Jun 15].  Back to cited text no. 16
    



 
 
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