Alcohol Issues in the Hospital R. Janan Markee November 5th, 2008
Outline • Overview of the alcohol problem • The role of primary care physicians and hospitalist • Alcohol withdrawal syndrome • Medical treatments of alcohol withdrawal • Issues in ICU • Alcohol and Seizures
Case • 46 yo male admitted after 4 witnessed tonic-clonic seizures at home • Chronic alcohol use, quit 2 days prior to admission • History of alcohol withdrawal seizures • Admitted to ICU • Required significant benzodiazepines • Transferred to floor with sitter • Haldol for agitation • Depakote
“At the Boston City Hospital alcoholism is among the commonest medical diagnoses made” Moore. NEJM. 1939
The Alcohol Problem • 7-8% of all Americans at any time • Lifetime prevalence of alcohol abuse 17% • Patients in primary care 20-36% • Alcohol related hospital admission 15-26% • Estimated $185 billion in alcohol related medical costs yearly • 15% of all health care costs Hasin. Arch Gen Psychiatry 2007;64:830-842.
Worldwide Issue • England had 100% increase in alcohol related admissions over past 10 years • Increase in alcohol use in developing countries • Estimated 2.3 million premature deaths yearly worldwide www.who.topics/alcohol
Alcohol Abuse DefinitionDSM-IV One of following: • Failure to fulfill major obligations at work, school or home • Recurrent use when physically hazardous • Recurrent legal problems • Recurrent social or interpersonal problems
Alcohol Dependence (Alcoholism) DSM-IV Three of following • Tolerance • Withdrawal • Large amounts over a long period • Unsuccessful efforts to cut down • Time spent in obtaining the substance replaces social, occupational or recreational activities • Continued use despite adverse consequences 30% male subject with alcohol abuse met criteria for dependence four years later Hasin. Am J Psychiatry. 1990.
Heavy Alcohol Use • Women • 7 drinks per week • Greater 4 drinks per day • Men • 14 drinks per week • Greater 5 drinks per day
Alcohol Discussions in Primary Care Practices • 65-88% physicians ask about alcohol use at first visit • 13% use formalized alcohol screening tools • 34% screen patients annually • 24% patients with alcohol dependence receive treatment Friedmann . J Gen Intern Med. 2000;15(2):84-91 Spandorfer.. J Fam Pract 1999.
Primary Care InterventionCochrane Review 2007 • Brief 5-15 minute intervention for patients presenting not for alcohol related issues • Feedback on harms • Identification of high risk situations • Coping strategies • Found overall lower alcohol consumption in group receiving intervention • Clear effect for men, not women • Longer counseling duration had little additional effect Kaner EF. Cochrane Database of Systematic Reviews 2007,
Treatment Programs for Alcohol Disorders • Positive outcomes among individuals who received treatment • 70% with reduction in number of drinking days and improved health status within 6 months • Improvement in family functioning, marital satisfaction, psychiatric impairments Project MATCH research group. J Stud Alcohol 1997.
How good are we at identifying hospitalized patients with alcohol related issues?
Detection of Alcohol Use Disorders in General Hospital Admissions in the United States Arch Int Med 2004 • Inpatient, nonfederal, general hospitals in US • Compared rates of hospital documented alcohol use vs interview positive admissions • Results • Detection rates 40-57% for alcohol related disorders • Referral rates for treatment • 50% for physician detected • 21% overall Smothers. Arch Int Med 2004
Low Hospital Detection Rates • Multiple studies over years • Physician issues • Lack of knowledge and poorly equipped • Attitudes and values inconsistent with treatment • Problems communicating about alcohol issues and other ‘sensitive’ issues Rumpf. Gen Hosp Psychiatry. 1998.
Hospital Critical in Detecting Alcohol Problems • Patients ready to modify alcohol behavior • 16% general population • 43% inpatients Rumpf.. Gen Hosp Psychiatry. 1999.
“Hospitalization provides an excellent opportunity for identifying alcohol problems among patients and providing them with alcohol intervention or treatment services.” Rumpf. Motivation to change drinking behavior: comparison of alcohol dependent individuals in a general hospital and a general population sample. Gen Hosp Psychiatry. 1999.
Withdrawal • Unclear why some people withdrawal • An experimental study of the etiology of “rum fits” and delirium tremens- 1955 • Alcohol 7-34 consecutive days developed minor withdrawal symptoms • Alcohol 48-87 consecutive days resulted in major withdrawal symptoms in 5 of 6 subjects • Most patients drink episodically Isbell. Q J Stud Alcohol. 1955.
Withdrawal • 13-71% persons experience significant symptoms of alcohol withdrawal • Hospitalized patients without pharmacologic treatment • 15% seizures • 15% DT Saitz. Clin Med N America. 1997
Mechanism of Withdrawal Alcohol withdrawal leads to CNS overactivity: • Alcohol enhances GABA (inhibitory) • Decreased GABA receptors • Withdrawal leads to less inhibitory • Inhibits glutamate via NMDA receptors (excitatory) • Upregulation of NMDA receptors • Withdrawal leads to hyperexcitability Lejoyeus. Alcohol Alcohol. 1998
Delirium Tremens • 5-24 % patients who are withdrawing from alcohol • Hallucinations, disorientation, tachycardia, hypertension, low grade fever, agitation, diaphoresis • Mortality 5%
Risk Factors for Delirium Tremens • History of sustained drinking • Greater number of days since last drink • Previous DT • Acute medical illness • Ataxia • Polyneuropathy • Elevated ALT and GGT Wetterling. Alcohol Clin Exp Res. 1994. Lee, JH. J Gastroenterol Hepatol. 2005. Ferguson. J Gen Intern Med 1996
Treatment Alcohol Withdrawal • Two major goals • Help patient achieve detoxification in a manner that is safe and comfortable • Enhance patient’s motivation for abstinence and recovery
Benzodiazepines • Treatment of choice for AWS • Improved outcomes for severity of withdrawal, occurrence of DT and seizures • Promote binding of GABA to receptor and increase frequency of receptor opening
Benzodiazepines • 1969: treatment of the acute alcohol withdrawal state: A comparison of four drugs. • Chlordiazepoxide, Hydroxyzine, chlorpromazine, thiamine vs placebo • Significantly fewer seizures and DT with Chlordiazepoxide Kaim. Am J Psych. 1969.
CIWAClinical Institute Withdrawal Assessment • Adapted from severity assessment scale (SSA) • Modified to apply every hour and to follow clinical course • Relies on patients ability to respond to questions • 7 of 10 questions require patient answers • Validity established by comparing nurses CIWA score to physicians assessment Shaw, J. M. (1981) Development of optimal treatment tactics for alcohol withdrawal. I: Assessment and effectiveness of supportive care. Journal of Clinical Psychopharmacology1, 382ñ387.[ISI][Medline]
Individualized Treatment of Alcohol WithdrawalJAMA 1994 • Double-blinded randomized trial • 100 inpatients admitted for treatment of alcohol withdrawal • Able to give informed consent • Excluded if concurrent medical illness requiring hospitalization • Scheduled chlordiazepoxide vs chlordiazepoxide prn (symptoms triggered therapy) Saitz. JAMA 1994. 272.
* No difference in severity of withdrawal or incidence of seizures or DT
Symptoms Triggered vs Fixed Doses of Benzodiazepine for Alcohol WithdrawalArch Int Med 2002 • 117 patients in alcohol detoxification unit • Excluded if greater than 72 hours since last drink or major medical comorbidities • Symptom triggered oxazepam vs fixed doses oxazepam • One episode seizure in symptom group Daeppen. Symptoms Triggered vs Fixed Schedule Doses of Benzodiazepine for Alcohol Withdrawal. Arch IN Med 2002 162.
Failures of CIWA • Case studies of patients failing CIWA • No history of alcohol use • Unable to communicate Bostwick. Psychosomatics. 2004.
Inappropriate Use of Symptom Triggered Therapy- (STT) • Chart review of 124 hospitalized patients who received STT according to CIWA • Appropriate use of STT • Intact verbal communication • Recent alcohol use Hecksel. Mayo clin proc 2008
Results • 48% met both inclusion criteria • Those who did not meet criteria • 14% drinkers, could not communicate • 55% could communicate, but did not drink • 31% met neither criterion • 55% had delirium from other cause
Comments • Lack of collateral and individual sources of history • Not considering other causes of delirium • Concern over use of protocols in diverse settings and applying protocols inappropriately
Consider scheduled benzodiazepines • Seizure or history • DT or history • Prolonged heavy alcohol consumption • Patient unable to communicate
Alcohol Withdrawal in ICU • Many of studies excluded patients in the ICU • 21% admissions to ICU alcohol related, with AWS most common • Often see benzodiazepine resistant AWS: greater than 40mg diazepam per hour • Mechanism altered structure of GABA Areceptor and downregulation of receptor expression Marik. Alcohol Alcohol 1996
Barbiturates for AWS • Studies show beneficial effects for treatment of alcohol withdrawal and DT • Increase duration of GABA receptor opening • Inhibit glutamate receptors Hoffman. Metab Brain Dis. 1995.
A Strategy of Escalating Doses of Benzodiazepines and Phenobarbital Administration Reduces the Need for Mechanical Ventilation in Delirium Tremens • Retrospective cohort study 95 patients • Subjects admitted to medical ICU solely for treatment of severe alcohol withdrawal • Initiated guidelines for escalating doses of diazepam in combination with phenobarbital • Compared preguidelines vs postguidelines Gold. CCM. 2007.
Postguidelines Results • Increased dose of total diazepam 248 vs 562mg • Increased maximum diazepam dose 32 vs 86mg • Increased phenobarbital use 17 vs 58% • Reduction in need for mechanical ventilation 47 vs 22% • Only one patient intubated for sedation • Intubation associated with longer ICU LOS 6.4 vs 3.1 • Higher incidence of nosocomial pneumonia 55 vs 12%
ICU • Consider use of phenobarbital in benzodiazepine resistant alcohol withdrawal syndrome
Anticonvulsants • Used for over 35 years for treatment of AWS • Europe • Mechanism: facilitate GABA inhibitory neurotransmission • Multiple studies comparing fixed doses anticonvulsants vs. placebo • Superior to placebo • Few studies comparing symptoms triggered benzodiazepine vs. anticonvulsants Prince. Am J Health Syst Pharm. 2008
Divalproex in Alcohol Withdrawal • Randomized double blind placebo controlled trial • 36 hospitalized patient moderate alcohol withdrawal • All received oxazepam and had more benzodiazepine available • Randomized to Divalproex 500 TID vs placebo • Results: significantly less oxazepam in divalproex group Reux JP. Alcohol clin Exp Res. 2001.
Double-Blind Controlled Trial Comparing Carbamazepine to Oxazepam Treatment of Alcohol Withdrawal • 86 patients admitted to VA with moderate-severe AWS without significant comorbidities • Randomized to carbamazepine 200mg QID vs oxazepam 30mg QID • Carbamazepine • As effectve as oxazepam • Lower ‘global distress scores’ Malcolm. Am J Psychiatry. 1989
Anticonvulsants for Alcohol Withdrawal Cochrane Review 2005 • 48 studies, 3600 patients • Variety of outcomes and different rating scales • Could not draw conclusions about effectiveness and safety of anticonvulsants
Cochrane Review Continued • Comparing cabamazepine vs benzodiazepines • Based on 260 patients • Statistically significant protective effect for carbamazepine • Non significant decrease in seizures • Less side effects • Need for larger well designed study
Summary • Use of carbamazepine or valproic acid for treatment of AWS can not be recommended • Need for larger well designed randomized control trials Lum. Annals Pharmacother 2006.