Treatment Of Alcohol Withdrawal Syndrome: Dexmedetomidine Vs Diazepam In A Hospital O'horán

The cessation of alcohol consumption of people suffering from alcohol abuse frequently leads to the development of an alcohol withdrawal syndrome (AWS).

The ethylic suppression syndrome is defined as the appearance of two or more data of autonomic hyperactivity, nausea, hallucinations and seizures associated with the cessation of alcohol consumption. For its evaluation, the CIWA-Ar scale is used, which guides the treatment based on benzodiazepines but with many adverse effects, so sedatives have been tried, among them dexmedetomidine, an alpha-agonist with action in the locus caeruleus, with variable results. Objectives: The investigators aimed to compare the DEX vs. Diazepam, for moderate disease, applying the CIWA-Ar scale, in participants with severe to moderate AWS. Methodology: 40 participants with CIWA-Ar greater than 10 points, the investigators are collected and randomized into two groups: one under treatment with diazepam (Group Diazepam) and another with dexmedetomidine (Group Dexmedetomidine), until the CIWA-Ar was reduced to less than 10, and adverse effects the investigators also reported. The analysis was done with student t. Results: The average duration of treatment with diazepam was 5.5 days (IC 95 = 6.6-3.8), the average duration of treatment with dexmedetomidine was 3.1 days (95% CI = 4.5-1.7), with a significant difference ( p = 0.0016). In the group with diazepam 60% presented adverse effects and in the group with dexmedetomidine 25% presented them, with a significant difference (p = 0.04). Conclusion: dexmedetomidine was superior to diazepam for the treatment of moderate-severe alcohol withdrawal with fewer adverse effects.

KEY WORDS: Alcohol dependence · Alcohol withdrawal syndrome · Dexmedetomidine · Diazepam · Benzodiazepines

Study Overview

• Status: Completed
• Conditions: Alcohol Withdrawal Delirium
• Intervention / Treatment: Drug: Dexmedetomidine 0.004 MG/ML; Drug: Diazepam Injectable Solution

Detailed Description

Alcohol withdrawal syndrome AWS (Alcohol Withdrawal Syndrome), is defined as the appearance of two or more data of autonomic hyperactivity, nausea, hallucinations and seizures associated with cessation of alcohol consumption. For its evaluation, the CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol) scale is used, which guides the treatment based on benzodiazepines but a disadvantage is the related adverse effects, for which other pharmacological strategies of sedation have been tried, among them Dexmedetomidine (DEX).

OBJECTIVES:

The investigators aimed to compare the DEX vs. Diazepam, for moderate disease, applying the CIWA-Ar scale, in participants with severe to moderate AWS (Alcohol Withdrawal Syndrome).

MATERIALS:

Prior authorization from the ethics committee of O'Horán Hospital, Yucatán, Mexico. No. Registration CEI-011-1-17, and signature of informed consent. A randomized clinical trial was carried out in the Adult Emergencies service during the period July 2017-July 2018. Forty participants with CIWA-Ar greater than 10 points participated. The administration of:

A) Diazepam 5-20 mg IV. B) DEX 0.2-0.7 mcg / Kg / min., until the CIWA-Ar scale decreases to <10.

The investigators are excluded minor patients, mild CIWA-Ar category, previous medication, participants with severe cranial encephalic trauma (TBI) or mechanical ventilation requirement, with chronic liver failure category C in the Child-Turcotte-Pugh classification.

RESULTS

The CIWA Ar scale average for admission was 23 points, the lowest of 10 points and the highest of 38 points. The average number of days consuming alcohol prior to hospital admission was 131.9, with the highest average in the group that used dexmedetomidine; the average number of days after having suspended the intake until hospital admission was 1.7 days, being slightly higher in the group that used diazepam; the shortest time was 6 hours and the longest of a week without being related to the CIWA Ar score.

The average duration of treatment with diazepam was 5.5 days (IC 95 = 6.6-3.8), The average duration of treatment with dexmedetomidine was 3.1 days (95% CI = 4.5-1.7) After applying t student a significant difference was found in the number of days in favor of dexmedetomidine (p = 0.0016)

CONCLUSIONS

The investigators found that DEX at conventional doses, for the treatment of moderate-severe alcohol withdrawal in terms of reducing the CIWA-Ar scale, in fewer days and with fewer adverse effects and complications.

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• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Ciudad de Mexico, Mexico, 4780000
    • Nayely Garcia Mendez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who received dexmedetomidine during their Emergency stay
• Patients who received diazepam during their Emergency stay
• CIE-10 codes consistent with alcohol withdrawal during hospitalization
• CIWA-A score >10 points

Exclusion Criteria:

• comorbid disease, including several with CNS trauma or cerebrovascular accidents, one with end-stage metastatic carcinoma, and one patient with severe sepsis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Dexmedetomidine; Dexmedetomidine. Dexmedetomidine use 400 mcg in 100 cc 0.9% physiological solution in continuous infusion starting at a dose of 0.2 mcg / kg / hr titrating until reaching a decrease in the adrenergic response, with a maximum dose of 0.7 mcg / kg / hr7. Dosage form: DEX 0.2-0.7 mcg/Kg/min.	Drug: Dexmedetomidine 0.004 MG/ML; Experimental studies and single case reports suggest the α2-agonist dexmedetomidine is effective in managing the autonomic symptoms seen with alcohol withdrawal.
Active Comparator: Diazepam; Dosage form: Diazepam 5-10 mg IV, steps until a maximum dose of 120 mg diazepam	Drug: Diazepam Injectable Solution; diazepam start with 5-20 mg IV as a dose response, steps until a maximum dose of 120 mg diazepam.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Alcohol Withdrawal Scoring	Total Score = 0 - 9: absent or minimal withdrawal 10 - 19: mild to moderate withdrawal more than 20: severe withdrawal	dosing, total dose per 24 hours period for each patient, limited to 10 days
Average Diazepam Received (mg)	Dosis total: Diacepam 5-20 mg IV	Limited to 10 days
Average Dexmedetomidine Received (mg)	Infusión: DEX 0.2-0.7 mcg/Kg/min	dosing, total dose per 24 hours period for each patient, limited to 10 days
heart rate average	mean values per 24 hours period for each patient	24 hours
Systolic blood pressure average	mean values per 24 hours period for each patient	24hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
days of hospital stay	Duration in days of hospital stay	24 hours limited to 10 days

Collaborators and Investigators

• Sponsor: Centro Medico Nacional La Raza, IMSS
• Collaborators: Universidad de La Frontera

Publications and helpful links

General Publications

• Yost DA. Alcohol withdrawal syndrome. Am Fam Physician. 1996 Aug;54(2):657-64, 669. Erratum In: Am Fam Physician 1996 Dec;54(8):2377.
• García-Méndez N, Briceño-Santana M, Totomoch-Serra A, Manterola C, Otzen T, Valdez PS, Campos-Durán R, Reyna GC. The hemodynamic effects of diazepam versus dexmedetomidine in the treatment of alcohol withdrawal syndrome: A randomized clinical trial. Med Clin (Barc). 2021 Dec 24;157(12):561-568. doi: 10.1016/j.medcli.2020.09.023. Epub 2021 Jan 8. English, Spanish.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): August 31, 2018

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: March 14, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Alcohol dependence; Dexmedetomidine; Diazepam; Alcohol withdrawal syndrome; Benzodiacepines
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Nervous System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Poisoning; Alcohol-Induced Disorders; Neurotoxicity Syndromes; Alcohol-Induced Disorders, Nervous System; Substance Withdrawal Syndrome; Alcohol Withdrawal Delirium; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Antiemetics; Gastrointestinal Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Neuromuscular Agents; Muscle Relaxants, Central; Dexmedetomidine; Diazepam
• Other Study ID Numbers: CEI-011-1-17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No