Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol

Wong, Adrian; Benedict, Neal; Lohr, Brian; Pizon, Anthony F.; Kane‐Gill, Sandra L.

doi:10.1016/j.drugalcdep.2015.07.005

Cited by 27 publications

(34 citation statements)

References 18 publications

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“…Propofol has general anesthetic effects that often require intubation and mechanical ventilation. Its use is therefore restricted to the intensive care unit making this agent an adjunct therapy for refractory cases of AWS 3, 6, 80, 90, 91. Its application and experience in AWS is limited to only a few cases and rebound of withdrawal symptoms soon after stopping propofol infusion has been reported 10…”

Section: Therapymentioning

confidence: 99%

Alcohol withdrawal syndrome: mechanisms, manifestations, and management

et al. 2016

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The alcohol withdrawal syndrome is a well‐known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking in patients suffering from alcohol use disorders (AUDs). AUDs are common in neurological departments with patients admitted for coma, epileptic seizures, dementia, polyneuropathy, and gait disturbances. Nonetheless, diagnosis and treatment are often delayed until dramatic symptoms occur. The purpose of this review is to increase the awareness of the early clinical manifestations of AWS and the appropriate identification and management of this important condition in a neurological setting.

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Section: Therapymentioning

confidence: 99%

Alcohol withdrawal syndrome: mechanisms, manifestations, and management

et al. 2016

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“…The second study, however, produced conflicting results. These authors found that the use of propofol was associated with decreased short‐term BZD requirements but increased time to resolution, duration of mechanical ventilation, and ICU and hospital LOS. However, propofol‐treated patients also had increased seizures, hallucinations, and DT, which may have indicated a higher severity of RAW.…”

Section: Discussionmentioning

confidence: 98%

“…Various alternative agents have been studied in the treatment and prevention of AWS, including barbiturates, antipsychotics, α 2 ‐agonists, β‐blockers, and anticonvulsants . Barbiturates, such as phenobarbital, may be effective in the treatment of withdrawal‐related seizures and when providing higher, initial doses of agents that bind to the GABA A receptor to prevent the development of AWS symptoms .…”

Section: Background and Objectivesmentioning

confidence: 99%

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Propofol for Treatment of Refractory Alcohol Withdrawal Syndrome: A Review of the Literature

et al. 2016

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The authors evaluated all available evidence on the use of propofol as an adjuvant for the treatment of resistant alcohol withdrawal syndrome (AWS) in comparison to other therapies. A comprehensive PubMed search (1966-December 2015) was conducted using the search terms propofol, alcohol withdrawal, and drug therapy. Articles were cross-referenced for other citations. Clinical studies, case series, and case reports published in the English language assessing the use of propofol in adult patients for treatment of AWS were reviewed for inclusion. Propofol is a sedative-hypnotic that exerts its actions through agonism of GABAA receptors at a different binding site than benzodiazepines and reduces glutamatergic activity through N-methyl-d-aspartase (NMDA) receptor blockade. Dosages from 5 to 100 μg/kg/minute reduced AWS symptoms with frequent development of hypotension and requirement for mechanical ventilation. Patients on propofol often experienced longer durations of mechanical ventilation and length of stay, which may be attributed to more-resistant cases of AWS. When propofol was compared with dexmedetomidine as adjuncts in AWS, both agents showed similar benzodiazepine- and haloperidol-sparing effects. Dexmedetomidine was associated with more numerical rates of bradycardia, while propofol was associated with more numerical instances of hypotension. Dexmedetomidine was used more frequently in nonintubated patients. The available data assessing the utility of propofol for AWS exhibited significant heterogeneity. Propofol may be useful in a specific population of patients with AWS, limited to those who are not clinically responding to first-line therapy with benzodiazepines. Specifically, propofol should be considered in patients who are refractory to or not candidates for other adjuvant therapies, patients already requiring mechanical ventilation, or those with seizure activity or refractory delirium tremens. In severe, refractory AWS, adjuvant therapy with propofol may be considered but requires further research to recommend its use either preferentially or as monotherapy.

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“…К таким больным относятся пациенты с син-дромом отмены алкоголя (СОА) -хроническая алкогольная интоксикация приводит к повреждению печени, повыше-нию толерантности к снотворным средствам, высокому риску развития лекарственной зависимости [12][13][14][15]. Как следствие, даже терапевтические дозы могут плохо перено-ситься больным.…”

Section: Introductionunclassified

Pharmacogenetic evaluation of adverse events’ risk in patients with alcohol withdrawal syndrome taking bromdihydrochlorphenylbenzodiazepine: The role of CYP2C19 gene polymorphisms

Ivashchenko¹,

Ryzhykova²,

Созаева³

et al. 2017

W J Person Med

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1 1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия 2 ГБУ «Московский научно-практический центр наркологии» ДЗМ, Москва, Россия ВВЕДЕНИЕ. Бромдигидрохлорфенилбензодиазепин -отечественный транквилизатор, широко применяемый в психиа-трии, неврологии, наркологии и общей медицине. В частности, данный препарат используется при купировании синдрома отмены алкоголя (СОА). Изофермент CYP2C19 участвует в метаболизме многих бензодиазепинов, поэтому его ген может быть включен в фармакогенетическое исследование бромдигидрохлорфенилбензодиазепина. Ранее не проводились ис-следования роли полиморфизмов гена CYP2C19 как биомаркеров безопасности данного препарата.МЕТОДЫ. В исследование были включены 102 пациента мужского пола с диагнозом неосложненного СОА (F10.30 по МКБ-10). Динамическое наблюдение длилось 6 сут, в течение которых пациенты принимали бромдигидрохлорфенилбен-зодиазепин (феназепам). Часть пациентов (n=38) принимали дополнительно паглюферал (комбинированный препарат, содержит фенобарбитал, кофеин-бензоат натрия, папаверин, бромурал) и/или карбамазепин. От каждого пациента было получено 5 мл венозной крови для генотипирования: с применением полимеразной цепной реакции в реальном времени определялось носительство полиморфных вариантов гена CYP2C19*2 (rs4244285), *3 (rs4986893) и *17 (rs12248560). Безо-пасность терапии оценивалась при помощи Шкалы оценки нежелательных эффектов -UKU Side Eff ects Rating Scale. Анализ данных проводился в программном пакете SPPS Statistics 21.0.РЕЗУЛЬТАТЫ. У носителей CYP2C19*2 GA+AA по сравнению с гомозиготами GG значимо чаще наблюдались такие неже-лательные побочные реакции (НПР), как «полиурия/полидипсия» средней степени выраженности (33,3% vs 9%, p=0,016) и «сердцебиение/тахикардия» (16,7% vs 3,8%, p=0,018). Наблюдаемая ассоциация «Полиурии/полидипсии» с генотипами CYP2C19*2 GA+AA сохранялась в подгруппе «Комбинированная фармакотерапия» (37,5% vs 0%, p=0,006). Полиморфизм CYP2C19*17 на уровне слабого тренда ассоциировался с меньшей частотой НПР «полиурия/полидипсия» среди пациентов, принимавших бромдигидрохлорфенилбензодиазепин в виде монотерапии -носители аллели T отмечали НПР в 16,9% слу-чаев, тогда как гомозиготы CC -в 24,2% (p=0,067).ВЫВОДЫ. Обнаружены значимые ассоциации полиморфизма CYP2C19*2 с отдельными НПР при приеме бромдигидро-хлорфенилбензодиазепина в составе терапии СОА. Не отмечено значимой роли CYP2C19*17 в прогнозировании риска развития НПР бромдигидрохлорфенилбензодиазепина. Ген CYP2C19 является значимым предиктором безопасности бром-дигидрохлорфенилбензодиазепина и нуждается в дальнейшем изучении.КЛЮЧЕВЫЕ СЛОВА: фармакогенетика; синдром отмены алкоголя; бензодиазепиновые транквилизаторы; CYP2C19

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Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol

Cited by 27 publications

References 18 publications

Alcohol withdrawal syndrome: mechanisms, manifestations, and management

Alcohol withdrawal syndrome: mechanisms, manifestations, and management

Propofol for Treatment of Refractory Alcohol Withdrawal Syndrome: A Review of the Literature

Pharmacogenetic evaluation of adverse events’ risk in patients with alcohol withdrawal syndrome taking bromdihydrochlorphenylbenzodiazepine: The role of CYP2C19 gene polymorphisms

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