intravenous ethanol for the treatment of alcohol withdrawal syndrome in critically ill patients

Intravenous Ethanol for the Treatment of Alcohol Withdrawal Syndrome in Critically Ill Patients

Brian Hodges, Pharm.D., and Joseph E. Mazur, Pharm.D.

Critically ill patients with alcoholism are at greater risk of morbidity andmortality from alcohol withdrawal syndrome than are patients withoutalcoholism. Benzodiazepines are considered the drugs of choice for theprevention and treatment of alcohol withdrawal syndrome, but some studieshave suggested that intravenous ethanol may be as effective as those agents, aswell as being less sedating. We evaluated the evidence regarding the use ofintravenous ethanol for the prevention and treatment of alcohol withdrawalsyndrome in critically ill patients in order to determine its role in this patientpopulation. Because of the paucity of well-designed clinical trials, andbecause of intravenous ethanol’s questionable efficacy, inconsistentpharmacokinetic profile, and relatively narrow therapeutic index, routine useof this drug is not recommended in critically ill patients who have alcoholwithdrawal syndrome or are at risk for it.Key Words: alcohol withdrawal syndrome, intravenous ethanol, CIWA-Ar,serum ethanol concentrations, benzodiazepines, delirium tremens.(Pharmacotherapy 2004;24(11):1578–1585)

OUTLINE

Alcohol Withdrawal StudiesDiscussionConclusion and Recommendations

Alcohol-use disorders are common amonghospitalized patients. An estimated 15–20% ofsuch patients are ethanol dependent and up tohalf of all traumatic injuries occur while thevictim is under the influence of alcohol.1–5 Theserates have been higher among certain types ofpatients, such as those undergoing resection ofupper digestive tract tumors.6 Critically illpatients with alcoholism are at greater risk ofmorbidity and mortality than are patientswithout alcoholism. Among the major compli-cations that may occur is alcohol withdrawal

syndrome.The first signs and symptoms of alcohol

withdrawal syndrome are manifestations ofautonomic hyperactivity caused by abstinencefrom alcohol. Tremors, sweating, nausea,vomiting, tachycardia, hypertension, anxiety, andagitation commonly occur during withdrawal.Patients usually maintain a clear sensoriumduring this phase of the syndrome, althoughillness, injury, metabolic disorders, and drugadministration may hinder accurate assessmentof the syndrome in the intensive care unit.

In the setting of abrupt discontinuation ofheavy, chronic drinking, approximately 25% ofpatients will develop symptomatic alcoholwithdrawal syndrome requiring drug therapy.7

Although the severity of the symptoms rangesfrom anxiety to delirium tremens, studies haveshown that surgical patients with alcoholwithdrawal syndrome have a 3-fold increased riskof postoperative mortality and increasedmorbidity due to cardiovascular and pulmonarycomplications.7, 8 It has also been observed thatthe presence of concomitant critical illness or

From the Department of Pharmacy Services, College ofPharmacy, Medical University of South Carolina,Charleston, South Carolina (both authors).

Address reprint requests to Joseph E. Mazur, Pharm.D.,Department of Pharmacy Services, College of Pharmacy,Medical University of South Carolina, 150 Ashley Avenue,Room 613, P.O. Box 250584, Charleston, SC 29425; e-mail:[email protected].

INTRAVENOUS ETHANOL FOR ALCOHOL WITHDRAWAL SYNDROME Hodges and Mazur

injury predisposes patients to have morecomplicated withdrawal episodes and a higherprevalence of delirium tremens.9

It is difficult to diagnose alcohol withdrawalsyndrome in critically ill patients, especiallythose who have pain and delirium, which arecommonly encountered in the intensive careunit. After a patient has been identified ashaving alcohol withdrawal syndrome or as beingat high risk for it, the pharmacotherapeuticregimen should be designed to achieve threegoals.10 The first goal is to keep the patientcomfortable, awake, calm, and cooperative. Thismay not always be practical in patients requiringlarge doses of sedative drugs in order to maintain

control of the symptoms of alcohol withdrawalsyndrome. The second goal is to prevent majorcomplications, such as severe autonomicsymptoms, hallucinations, and seizures. Thethird goal is to reduce long-term central nervoussystem complications that may occur due torepeated withdrawal episodes.

Because they are most likely to preventcomplicated alcohol withdrawal syndrome and toprovide symptomatic relief, agents that directlyor indirectly increase transmission of �-aminobutyric acid are the most frequently usedin patients with alcohol withdrawal syndromewho are in the intensive care unit.11 Benzodia-zepines are typically the treatment of choice for

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Table 1. Summary of Published Clinical Trials and Case Reports on the Use of Intravenous Ethanol for the Treatment andPrevention of Alcohol Withdrawal Syndrome

No. of Serum MonitoringPatients Study Design Performed Treatment Regimen Key Findings4918 Prospective, Yes Promazine (n=13), Ethanol treatment resulted in

randomized, chlordiazepoxide (n=12), progression of AWS or concomitantcontrolled chloral hydrate and complications in 7 (58%) of 12

paraldehyde (n=12), patientsethanol (n=12)

1976 Prospective, On admission Flunitrazepam- No major difference in developmentrandomized, clonidine (n=48) of symptomatic AWS, length of staycontrolled chlormethiazole- in ICU, or major intercurrent

haloperidol (n=49), complications; ↑ frequency offlunitrazepam- tracheobronchitis in chlormethiazole-haloperidol (n=50), haloperidol groupethanol (n=50)

2216 Prospective, Daily 10% ethanol in D5W None showed clear signs of AWSuncontrolled concentrations at 50–100 ml/hr

x 3–8 days

3715 Nonrandomized, On admission, 10% ethanol in D5W 17 (46%) of 37 patients responded touncontrolled 12 hrs after at 50 ml/hr x 96 hrs ethanol within 12 hrs, and 3 (8%)

infusion started, (mean duration) responded poorly or not at all;then every 24 hrs no complications

3219 Prospective, Blood, urine, i.v. ethanol i.v. ethanol failed to preventobservational expired air (dosages determined symptomatic AWS in 13 (41%)

by patients’ daily patients; 10 (77%) of the 13 patientsalcohol consumption) had progression to major medical

complications

1120 Prospective, Yes 30–299-g bolus dose of Prevention of AWS in 10 (91%) ofobservational 96% ethanol, then 11 patients; the eleventh patient

30–299 g/day x 1–9 days required dosage increases over a7-day period; no complicationsdue to ethanol substitution

121 Case report None documented Chlorpromazine added Vital signs normalized after ethanolto 5% ethanol treatment; no complications

622 Retrospective None documented Ethanol added to All patients had delirium tremens;case series chlorpromazine none received ethanol prophylaxis;

no deaths

223 Case report None documented 5% ethanol in D5W Rapid symptom control achieved;at 50–75 ml/hr no complications

AWS = alcohol withdrawal syndrome; D5W = 5% dextrose in water; ICU = intensive care unit.

PHARMACOTHERAPY Volume 24, Number 11, 2004

these patients.12–14 These agents reduce with-drawal severity, prevent the progression of alcoholwithdrawal syndrome to delirium tremens, anddecrease the prevalence of withdrawal-relatedseizures.12 However, some clinicians believe thatthe degree of sedation and respiratory depressioncaused by benzodiazepines is excessive and thatless sedating, alternative therapies would be ofgreat benefit in the assessment and treatment ofpatients with alcoholism after a major illness orinjury.15, 16

Intravenous ethanol may be an effective meansof preventing and treating alcohol withdrawalsyndrome while causing less sedation andrespiratory depression than benzodiazepines.15

Critical care textbooks have described relativelylow infusion rates as exerting “a calming effectamazingly quickly.”17

Alcohol Withdrawal Studies

A number of clinical trials and publishedreports exist on the use of intravenous ethanolfor the treatment and prevention of alcoholwithdrawal syndrome (Table 1). One of the firststudies to use intravenous ethanol in patientswith alcohol withdrawal syndrome was publishedin 1967.18 The study involved 49 men, aged31–71 years, who had been admitted to aVeterans Administration hospital and weresubsequently diagnosed with alcohol withdrawalsyndrome. Patients were randomly assigned toone of four treatment groups: promazinehydrochloride (13 patients), paraldehyde andchloral hydrate (12), ethanol (12), andchlordiazepoxide (12). Patients assigned to theethanol group were to be maintained in aconstant state of intoxication with a doseequivalent to 200 ml of 100% ethanol during thefirst 24 hours, with half administered orally individed doses and half as 5% ethanol in 5%glucose solution by continuous intravenousinfusion. The dosage was tapered gradually overat least 5 days (maximum daily doses wereequivalent to 600 ml of 100% alcohol) as patientsimproved symptomatically. Recovery without theworsening of symptoms of alcohol withdrawalsyndrome or the development of pneumoniaoccurred in 5 (39%) patients who had receivedpromazine, 5 (42%) who had received ethanol, 4(33%) who had received chlordiazepoxide, and11 (92%) who had received paraldehyde andchloral hydrate.

Ethanol treatment resulted in either progressionof alcohol withdrawal syndrome or concomitant

complications in 7 (58%) of 12 patients.18 Onepatient was not adequately sedated despite bloodalcohol concentrations of 0.3–0.38% (300–380mg/dl). The authors concluded that thecombination of enteral and parenteral ethanol isnot effective in treating alcohol withdrawalsyndrome and that it is in fact hazardous due toethanol’s narrow safety margin.

Only one randomized controlled trial exists, toour knowledge, comparing intravenous ethanolwith other drug regimens in an open-labelfashion for the prevention and treatment ofalcohol withdrawal syndrome in the intensivecare unit.6 A total of 197 alcohol-dependentpatients (minimum intake 60 g/day) undergoingresection of upper gastrointestinal carcinomaswere allocated randomly, on admission to theintensive care unit, to receive one of fourprophylactic regimens: flunitrazepam-clonidine(48 patients), chlormethiazole-haloperidol (49),flunitrazepam-haloperidol (50), or ethanol (50).The objective of this study was to identify anydifferences between the four regimens withrespect to length of stay in the intensive careunit, occurrence of symptomatic alcoholwithdrawal syndrome as determined by a score ofmore than 20 on the Clinical Institute forWithdrawal Assessment–Alcohol, Revised(CIWA-Ar), and the occurrence of majorcardiovascular and pulmonary complications.Patients were monitored for symptoms of alcoholwithdrawal syndrome with use of the CIWA-Aras administered by a blinded investigator. Patientsreceived a loading dose of their designatedtherapy, followed by a continuous infusion thatwas titrated to maintain a CIWA-Ar score of lessthan 20. The CIWA-Ar was administered once/hour for the first 24 hours and then 4 times/day.The investigators found no significant differencesbetween the four groups with respect to theoccurrence of symptomatic alcohol withdrawalsyndrome (p=0.4952): six (12.5%) patients inthe flunitrazepam-clonidine group, four (8.2%)in the chlormethiazole-haloperidol group, five(10%) in the flunitrazepam-haloperidol group,and two (4%) in the ethanol group. They alsodetected no significant differences in the lengthof stay in the intensive care unit or the frequencyof major intercurrent complications (p=0.1353).However, there was a significantly higher frequencyof tracheobronchitis and respiratory hypersecretionin the chlormethiazole-haloperidol group(p=0.0012). In the 50 patients who receivedintravenous ethanol, the median bolus dose was3 g (range 2–4 g), median maximum ethanol

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infusion rate was 48 mg/kg/hour (range 12–157mg/kg/hr), and median cumulative ethanol dosewas 316 g (range 40–1348 g).

The use of intravenous ethanol to preventalcohol withdrawal syndrome in the setting ofthermal injury was evaluated in a prospective,uncontrolled study of 153 patients.16 Of thosepatients, 22 (19 men, 3 women), aged 24–72years, were identified as having a daily alcoholintake of at least six 12-ounce cans of beer or 4ounces of liquor, or an equivalent intake of othertypes of alcoholic beverages. Patients were given10% ethanol in 5% dextrose in water at initialinfusion rates of 50–100 ml/hour to prevent ortreat alcohol withdrawal syndrome. Infusionrates were adjusted 1–2 times/day to maintainblood ethanol concentrations in the range of2–12 mg/dl. Once the decision was made todiscontinue ethanol therapy, the infusion wastapered over 24–36 hours. Patients receivedethanol at rates of 0.03–0.06 mg/kg/hour,resulting in blood ethanol levels of 2–8 mg/dl.None of the patients had clear signs of alcoholwithdrawal syndrome over the 3–8-day course ofthe infusion. Sedation due to ethanol wasreported in only one patient, who had hadsymptomatic alcohol withdrawal syndrome at thetime of entry into the study.

In another nonrandomized, uncontrolled study,conducted over 3 years and 3 months, 1602(72%) of 2219 trauma patients who wereadmitted to the hospital were tested for serumethanol levels, and measurable levels were foundin 685 (43%).15 Of these patients, 37 (34 men, 3women; mean age 46 yrs) were diagnosed ashaving alcohol withdrawal on the basis of clinicalobservation by physicians or nursing staff. Afterthe signs and symptoms of alcohol withdrawalbegan, patients were administered a 10% ethanolinfusion at a rate of 50 ml/hour. Patients wereexcluded from receiving intravenous ethanol ifthey had evidence of intracranial hemorrhage,spinal cord injury with neurologic deficit, liverdisease, active pancreatitis, or a history ofalcoholic pancreatitis. Patients were treated for48 hours once the infusion was titrated toachieve symptomatic control, and an attempt totaper the infusion was made over the subsequent48 hours. The mean duration of therapy withintravenous ethanol was 4 days (range 1–15days). The goal was to achieve symptomaticimprovement while maintaining undetectableserum ethanol concentrations. Concentrationswere to be monitored 12 hours after the initiationof ethanol therapy and then once/day, but these

levels were not reported. The effectiveness ofintravenous ethanol therapy was judged on thebasis of observations by the nursing staff andphysicians with regard to how quickly patientsresponded, as assessed with an ordinal scale. Ascore of 5 (very good) indicated that the patienthad responded within less than 12 hours,whereas a score of 1 (poor) represented aresponse within 48 hours or more. The averagetime to response was 14 hours (median 7 hrs,range 2–48 hrs). Of the 37 patients, 17 (46%)responded within 12 hours and 3 (8%)responded poorly or not at all. No complicationsor adverse effects were reported.

Thirty-two alcohol-dependent patients whounderwent elective gastrointestinal surgery oremergency surgery after trauma and weresubsequently admitted to the intensive care unitwere enrolled in a prospective, observationalstudy that included a post hoc analysis ofdifferent methods of monitoring ethanolconcentrations.19 All patients had a preoperativealcohol intake of at least 60 g/day. No patienthad major liver disease, heart failure, cardiacarrhythmia, infection, or symptomatic alcoholwithdrawal syndrome. Primary and secondaryoutcome measures were designed to evaluatemethods of monitoring ethanol concentrations inthe blood, urine, and expired air duringintravenous ethanol treatment, and to comparethe frequency of complications between patientswho had successful and unsuccessful prophylaxisfor alcohol withdrawal syndrome withintravenous ethanol in patients who achieved aCIWA-Ar score of more than 20. Of the 32 patients,13 (41%) had progression to symptomaticalcohol withdrawal syndrome; it occurred in 55%of patients who had surgery after trauma and in17% of those undergoing elective surgery. Themedian ethanol bolus dose (94 vs 73 g) andmedian maximum dose/day (94 vs 73 g/day) didnot differ significantly between the failure andsuccess groups. No significant differences in themean concentrations of whole arterial blood,venous blood alcohol, urinary alcohol, or exhaled-air alcohol were found between the two groups.No significant correlations were observedbetween maximum ethanol dose and clinicaloutcome among any of the methods for moni-toring ethanol concentrations. At least one majorcomplication occurred in 10 (77%) of the 13patients who developed symptomatic alcoholwithdrawal syndrome compared with two (11%)of the 19 who did not (p<0.001). Pneumoniawas the most frequent complication. Other

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complications, including wound infection, sepsis,heart failure, and bleeding, occurred only inpatients who had alcohol withdrawal syndrome.

In a retrospective study of postoperativeethanol substitution therapy in 11 patients withan admitted chronic drinking problem, a bolusdose intended to achieve a blood ethanolconcentration of 0.6 g/L (60 mg/dl) was followedby an infusion rate intended to achieve a steady-state concentration of 0.5–0.7 g/L (50–70 mg/dl).20

Dosages were based on the patient’s weight, theestimated volume of ethanol distribution, and theestimated ethanol elimination rate. Bloodethanol concentrations were obtained every 4hours on day 1 and every 6 hours thereafter. Theethanol elimination rate in these patients wasmuch higher than the estimated rate in studies ofhealthy volunteers.20 Ethanol dosages rangedfrom 6–33 g/hour, and mean minimum andmaximum blood ethanol concentrations of 0.37and 1.13 g/L (37 and 113 mg/dl), respectively,were achieved. The authors reported thatethanol substitution prevented alcohol with-drawal syndrome in 10 of the 11 (91%) patients;the eleventh patient required frequent dosageincreases over a 7-day period to control hissymptoms. Ethanol substitution appeared to beeffective even in patients with blood ethanolconcentrations below 0.2 g/L (20 mg/dl). Nocomplications related to the therapy werereported, although three patients had post-operative infection that resulted in two deaths.

The case of a 23-year-old man who receivedintravenous ethanol after sustaining multiplemusculoskeletal and thermal injuries while underthe influence of alcohol (blood alcoholconcentration 370 mg/dl on admission) wasreported in 1978.21 Two days after the accident,the patient was being operated on under generalanesthesia when he began to exhibit signs ofalcohol withdrawal syndrome, including hyper-tension and hyperthermia (rectal temperature104.4oF). The decision was made to treat thepatient with intravenous ethanol. He received250 ml of 5% ethanol in the first hour of therapyand improved symptomatically within 15minutes after the start of the infusion. Withinthe next 24 hours, his vital signs normalizedcompletely. Before the patient had additionalsurgery, he was given ethanol intravenously forprophylaxis, without complications. Over thecourse of his recovery, he was treated with slowlydecreasing doses of chlorpromazine andintravenous ethanol, without any complicationsor symptoms of alcohol withdrawal syndrome.

The use of intravenous ethanol for thetreatment of alcohol withdrawal syndrome ismentioned in a review of alcohol withdrawalsyndrome prevention in six surgical patients.22

The authors discuss the pharmacology, pharma-cokinetics, and potential therapeutic benefits ofethanol replacement in these patients and makereference to the use of intravenous ethanol intheir local institution. Delirium tremens occurredpostoperatively in all six patients, none of whomhad received ethanol prophylactically. None ofthe patients died. The authors attributed thisoutcome, at least in part, to the administration ofintravenous ethanol in five of these patients afterthey were diagnosed with delirium tremens.

The cases of an additional two surgical patientstreated with intravenous ethanol were describedin 1990.23 Both patients were men with a historyof heavy alcohol consumption. Both developedalcohol withdrawal syndrome postoperativelyand were treated initially with intramuscularchlordiazepoxide (a single dose of 75 mg in oneand 50 mg every 6 hours for an unreportedduration in the other). Both patients weresubsequently switched to treatment withintravenous ethanol; they were treated initiallywith 50–75 ml/hour of 5% ethanol in 5%dextrose in water, with the infusion rate taperedover the next 24–48 hours. Rapid symptomaticimprovement was achieved in both patients, andno complications related to the treatment werereported.

Discussion

A review of the literature pertaining to the useof intravenous ethanol in patients who havealcohol withdrawal syndrome or are at risk for itreveals great variation in the quality of themethodology and the results, making thoroughand fair evaluation of this drug difficult.

Even greater variability exists in the results ofprospective studies of use of intravenous ethanolin critically ill patients. Three groups of investi-gators reported that intravenous ethanol wasconsistently successful in either preventing orreversing alcohol withdrawal syndrome.15, 16, 20 Intwo of these studies, all of 22 patients with aburn injury had successful prophylaxis ortreatment16 and 29 (91%) of 32 patients withtrauma had successful treatment (17 of themwithin 12 hrs),15 respectively, with minimalcomplications. In the third study, which assessedthe use of population-based pharmacokineticparameters in the design of ethanol dosing

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regimens for alcohol-dependent patientsundergoing surgery, 10 (91%) of 11 patients withchronic alcoholism had successful prophylaxisfor alcohol withdrawal syndrome with ethanolsubstitution.20

These results are in contrast to those reportedin two controlled trials of ethanol use in criticallyill patients.18, 19 In the first of these studies, 7(58%) of 12 hospitalized patients who wererandomized to receive a combination of enteraland parenteral ethanol had progression of alcoholwithdrawal syndrome to delirium tremens orcomplications that the authors attributed toalcohol withdrawal syndrome or oversedation.18

In the second study, intravenous ethanol failed toprevent symptomatic alcohol withdrawalsyndrome in 13 (41%) of 32 patients afterelective or emergency surgery, and 10 (77%) ofthe 13 patients who had progression to alcoholwithdrawal syndrome experienced at least onemajor medical complication.19

In the only randomized, controlled trialpublished to date in which prophylactic use ofintravenous ethanol was compared with that ofbenzodiazepine-containing regimens in theintensive care unit, no significant difference wasobserved with respect to the occurrence of symp-tomatic alcohol withdrawal syndrome or majormedical complications.6 Although this mayrepresent therapeutic equivalence, it may alsoindicate a lack of power to detect a differencebetween the regimens. The authors stated that inorder to adequately power a study to compareonly two prophylactic regimens, a sample size ofat least 1000 patients would have been required.Therefore, no strong conclusions can be drawnbased on this study as to the effectiveness orineffectiveness of intravenous ethanol in theprevention or treatment of alcohol withdrawalsyndrome.

A number of reasons may account, at least inpart, for the marked variability in the results ofthese prospective studies, chief among thembeing methodologic differences. The patientpopulations are largely homogeneous (surgical ortrauma patients), which eliminates large numbersof other critically ill patients (e.g., medicallycritically ill). Methods used for intravenousethanol dosing have been remarkably variable inpublished reports of both prospective andretrospective studies. Regimens have included200 ml of 100% ethanol (a combination ofenteral and parenteral administration) over thefirst 24 hours, 50–100 ml/hour of 10% ethanol in5% dextrose in water, 50 ml/hour of 10% ethanol

in 5% dextrose in water, or individualized bolusdoses and infusion rates based on the populationpharmacokinetics of ethanol or the reportedamount of baseline alcohol consumption.15, 16, 18–20

One group of investigators did not report thestandard initial bolus dose or infusion rates, butthey documented a median intravenous bolus ofethanol of 3 g (range 2–4 g) and a medianmaximum ethanol infusion rate of 48 mg/kg/hour(range 12–157 mg/kg/hr).6 In all of these studies,rates were titrated based on patients’ symptomsof alcohol withdrawal syndrome.

The methods used in these studies to diagnoseand monitor patients with alcohol withdrawalsyndrome have included the objective applicationof criteria from the Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition fordiagnosis; the regimented use of the CIWA-Ar formonitoring; and the purely subjective clinicalobservations of investigators.16, 19 Although theCIWA-Ar has not been validated specifically foruse in critically ill patients, and whereas some ofthe symptoms that it evaluates are more likely tooccur in the absence of alcohol withdrawalsyndrome in the intensive care unit, it is anobjective, repeatable measure that has beenvalidated for use in detoxification centers and inthe general hospital setting.

The goals, durations, intensities, and methodsof monitoring alcohol concentrations also havediffered dramatically among studies. Goalconcentrations have ranged from undetectable inasymptomatic patients to maintaining a constantstate of intoxication with resultant concentrationsof 0.38% (380 mg/dl) in individual patients.15, 18

One group of investigators found that maintainingblood ethanol concentrations in the range of2–12 mg/dl, was successful in preventing alcoholwithdrawal syndrome.16 Two studies have beenconducted with the specific aims of identifyingcorrelations among ethanol dose, resultantconcentrations, and changes in the occurrence ofsymptomatic alcohol withdrawal syndrome.19, 20

However, neither study identified a consistentlyeffective dosing and monitoring strategy, and theauthors concluded that protocols for intravenousethanol should allow for much individualization.

Less variability exists in the results of anecdotalcase reports of intravenous ethanol use. Perhapsbecause of the nature of the cases that clinicianschoose to submit and journals decide to publish,these reports consist almost entirely of patients inwhom intravenous ethanol use was consideredhighly successful and who had no seriouscomplications.21–23

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In addition to difficulties in interpreting theavailable evidence regarding the effectiveness andsafety of intravenous ethanol, there are a numberof practical challenges. Of major concern is thatthe studies and cases published to date havefocused almost exclusively on surgical patientswho are critically ill, which raises the question ofhow this drug should be used in patients withprimarily medical illnesses. There are alsoindications that clinicians have had difficulty inidentifying appropriate situations in which to useintravenous ethanol.

A retrospective chart review in an urbanacademic medical center over a 6-month periodfound inconsistent documentation regarding theduration and total dose of intravenous ethanol ina heterogeneous patient population, according toa pharmacy database.24 A total of 68 patientswere identified as having received intravenousethanol, starting at a mean of 1.21 days afteradmission, for a median duration of 3 days. Theestimated mean total dose of absoluteethanol/patient was 261.7 ml (range 10–945 ml).Fifty patients received only intravenous ethanol,whereas 18 were later transitioned to enteralethanol. Only 10% of patients who receivedintravenous ethanol were referred to alcohol-cessation programs. The authors could notidentify consistent criteria for determining whypatients were treated with intravenous ethanol,and less than 40% of patients had at least onedocumented criterion that would have put themat risk for delirium tremens. The authorsconcluded that there is a need for a revision inpolicies related to the identification andtreatment of patients with known or suspectedalcohol-use disorders.

Conclusion and Recommendations

Despite several anecdotal reports of thesuccessful use of intravenous ethanol, data on itseffectiveness for prophylaxis and treatment ofalcohol withdrawal syndrome in critically illpatients have been inconclusive. Although someauthors have stated that ethanol is superior tobenzodiazepines in patients with alcoholwithdrawal syndrome, there have been only twosmall, randomized studies comparing theseagents. Neither study appears to have beenadequately powered to detect a difference amongthe treatments tested. In addition to questionableefficacy, ethanol exhibits inconsistent pharmaco-kinetics and a relatively narrow therapeuticindex.

Considering these facts, as well as the evidencethat benzodiazepines control symptoms ofalcohol withdrawal syndrome and preventcomplicated alcohol withdrawal syndrome in thebroader population, and that they are the drugsof choice for sedation and anxiety in mostcritically ill patients, we cannot recommend theroutine use of intravenous ethanol for thisindication in critically ill patients. Althoughclinicians will continue to administer intravenousethanol for the prevention and treatment ofalcohol withdrawal syndrome in patients whomthey do not wish to sedate, we recommend thatits use be avoided in such patients until a large,well-designed trial has been conducted.

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intravenous ethanol for the treatment of alcohol withdrawal syndrome in critically ill patients

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