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

Alcohol Withdrawal Delirium Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03877120
• Other study ID #: CEI-011-1-17
• Status: Completed
• Phase: Phase 4
• Start date: November 1, 2017
• Est. completion date: August 31, 2018

Study information

• Verified date: March 2019
• Source: Centro Medico Nacional La Raza, IMSS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

REFERENCES:

1. Anderson P, Lars M, Gauden G. Alchol in the Europen Union. Consume, harm and policy approaches. Edit. WHO. 2012

2. Nota descriptiva N° 349: Alcohol. Organización Mundial de la Salud. 2015.

3. Encuesta Nacional de Adicciones 2011: Reporte de Alcohol. Medina-Mora ME, Villatoro-Velázquez JA, Fleiz-Bautista C, et. Al. México: INPRFM; 2012.

4. Longo D, Fauci A, Kasper E, et al. Harrison: Principios de Medicina Interna. 18ª ed. McGraw-Hill. México. 2012.

5. Diagnostic and statistical manual of mental disorders. 5th edition. Washington, DC:

American Psychiatric Association; 2013. 947 pp.

6. Carson L, Kumar N, Wong-Mckinstry. Alcohol Withdrawal Syndrome. Critical Care. 2012.

7. Jawa R, Stothert J, Shostrom V, et al. Alcohol Withdrawal Syndrome in admitted trauma patients. The American Journal of Surgery (2014)208: 781-787

8. Sullivan J, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989. 84(11):1353-7.

9. Waye C, Wong M, Lee S. Implementation of a CIWA Ar Alcohol Withdrawal protocol in a Veterans Hospital. South Med Jour. 2015. 108(1):23-8.

10. Ramírez D, Sánchez G. Capacidad diagnóstica de las escalas de Cushman y AWS para supresión etílica. Med Int de Mex. 2013. 29(1): 26-31

11. Miller W, McCurdy L. A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of the acute alcohol withdrawal syndrome. Clin Ther 1984. 6(3):364-71.

12. Henrey G, Dery R, Bandes R. A prospective randomized trial of phenobarbital vs benzodiazepines for acute alcohol withdrawal. Am Jour Eme Med. 2011. 382-85.

13. Hughes D, VanWert E, LePori L. Propofol for benzodiazepine-refractory alcohol withdrawal in a non-mechanically ventilated patient. Am Jour Eme Med. 2014. 112.e3-e4.

14. Wong A, et al. Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal. J Crit Care. 2014.

15. Samuels E, Szabadi E. Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation. Curr Neuropharmacol. 2008; 6(3): 235-53.

16. 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 Psychiatr 2006, 28:362-363.

17. Rayner et al. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal. Annasl of intensive care. 2012. 2:12

18. VanderWeid L, Foster C, McLaren R. Evaluation of early dexmedetomidine addition to the standard of care for severe alcohol withdrawal in the ICU: A retrospective controlled cohort study. Jour Int Care Med. 2014. 1-7.

19. Frazee E, Personett H, Leung J, et al. Influence of dexmedetomidine therapy on the management of severe alcohol withdrawal síndrome in critically ill patients. Jour Crit Care. 2014. 198-302.

20. Crispo A, Daley M, Pepin J. Comparison of clinical outcomes in nonintubated patients with severe alcohol withdrawal síndrome treated with continuous-infusion sedatives: dexmedetomidine versus benzodiazepines. Pharm. 2014. 910-17.

21. Pita S. Determinación del tamaño muestreal. Cad Aten Prim. 1996. 138-44.

22. Farmacología Básica y clínica. P Lorenzo, A Moreno, Lizasoain, et al. 18ª ed. Editorial Panamericana. España. 2010.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: August 31, 2018
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Withdrawal Delirium
• Delirium
• Substance Withdrawal Syndrome

Intervention

Drug:
• Dexmedetomidine 0.004 MG/ML
Experimental studies and single case reports suggest the a2-agonist dexmedetomidine is effective in managing the autonomic symptoms seen with alcohol withdrawal.
• Diazepam Injectable Solution
diazepam start with 5-20 mg IV as a dose response, steps until a maximum dose of 120 mg diazepam.

Locations

Country	Name	City	State
Mexico	Nayely Garcia Mendez	Ciudad de Mexico

Sponsors (2)

Lead Sponsor	Collaborator
Centro Medico Nacional La Raza, IMSS	Universidad de la Frontera

Country where clinical trial is conducted

Mexico, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Average Diazepam Received (mg)	Dosis total: Diacepam 5-20 mg IV	Limited to 10 days
Primary	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
Primary	heart rate average	mean values per 24 hours period for each patient	24 hours
Primary	Systolic blood pressure average	mean values per 24 hours period for each patient	24hours
Secondary	days of hospital stay	Duration in days of hospital stay	24 hours limited to 10 days