Ethanol replacement protocol for the management of the hospitalized alcohol-dependent patient

Ethanol Replacement Protocol For The Management Of The Hospitalized Alcohol-Dependent Patient To administer a continuous intravenous infusion of ethyl alcohol for theprevention of the alcohol withdrawal syndrome (AWS) in hospitalizedalcohol-dependent patient.
To avoid generalized sedation and intoxication during the early diagnosisand treatment of acute illness in the hospitalized alcohol-dependentpatient.
To initiate a comprehensive program for substance abuse therapy andrehabilitation.
This protocol is to be administered to selected, acutely ill or injured patientsdeemed to be at risk for the development of the AWS who require hospitalization.
Once the patient has recovered from their acute illness/injury, alcohol abusecounseling and rehabilitation will be offered as part of a comprehensive programto manage the individual’s substance-related medical condition in collaborationwith the Addiction Rehabilitation Service and Department of Psychiatry.
BACKGROUND: Alcohol-dependent patients are frequently admitted to the trauma service for theacute care of injuries. Often, these injuries are a direct result of the abuse ofalcohol. The development of AWS greatly complicates the management ofhospitalized patients suffering from acute traumatic injury or illness. The currentpharmacologic therapy of choice for the in-patient management of the alcohol-dependent patient is the administration of a moderately long-actingbenzodiazepine (eg. Ativan). Patients commonly become sedated as a result ofthe benzodiazepine doses required to control the symptoms and signs of AWS.
The sedated, injured patient thus becomes bed-ridden, often times restrained,and is no longer able to co-operate with critical therapy needed to avoid medicalcomplications commonly seen in injured patients, such as deep venousthrombosis and respiratory dysfunction. Certain groups of patients may be morelikely to experience undesirable side effects of benzodiazepine agents, such asrespiratory depression. These groups include patients consuming largequantities of alcohol on a chronic basis, patients receiving narcotic-basedanalgesia, or those with compromised respiratory function. The goal of this protocol is to administer a non-sedating, dose of ethanol by intravenous infusion to patients that are at moderate-to-high risk of developingAWS. The therapeutic goal is two-fold: first to prevent AWS and second to avoida state of generalized sedation. This will allow the patient time to recover fromtheir acute injuries while avoiding the potential complications associated with theAWS and its treatment. Once the patient has recovered from their acute injuries,voluntary enrollment into a comprehensive program for alcohol treatment andrehabilitation will be offered. Should the patient choose to enroll into such aprogram, then a patient-specific therapeutic plan will be offered by AddictionRehabilitation Services (ARS).
The final choice regarding the pharmacologic management of the alcohol dependent patient in the acute care hospital setting is and remains theresponsibility of the physician of record. This protocol provides save andeffective guidelines for the administration of ethyl alcohol as alcohol replacementtherapy if the physician chooses this therapeutic option. Alcohol dependence is a complicated medical disease that requires a multidisciplinary approach toprovide state of the art care. The patient’s unscheduled admission into thehospital because of acute illness or injury represents a golden opportunity topositively intervene in this chronic disease process.
To identify the alcohol-dependent patient hospitalized because of acuteillness or injury.
To administer intravenous ethyl alcohol in a monitored setting to preventthe development of the AWS, avoid generalized sedation and permitdetoxification.
To obtain a substance abuse consultation and offer the patient the optionto enroll in a voluntary alcohol treatment and rehabilitation program.
PATIENT ELIGIBILITY: Patients at risk for development of the AWS.
1. Past medical history is significant for previous episode of AWS.
Cessation of alcohol use that has been heavy or prolonged (>1 month).
Risk for the AWS as determined by patient/family history.
BAL > 150mg/dL and clear sensoriumBAL ³ 300mg/dL Patients receiving any of the following medications with Disulfiram-like(Antabuse) effects: Bromocriptine (Parlodel), Cefamandole (Mandol), Cefaperazone(Cefobid), Chlorpropamide (Diabinese), Griseofulvin, Metronidazole(Flagyl), Procarbazine (Matulane) and Tolbutamide (Orinase).
Chronic alcoholic end-organ diseases; cirrhosis, portal hypertension,pancreatitis, cardiomyopathy, thrompbcytopenia due to splenomegaly,evidence of bone marrow suppression, chronic myopathy, chronicneuropathy, and Wernicke’s or Korsakoff’s syndrome.
Caution should be exercised for the following clinical conditions:
Type II diabetics (NIDDM) receiving sulfonylureas such asglyburide or glipizide (hypoglycemia), and metformin (lacticacidosis) Secondary causes for altered mental status must be excluded such as:hypoxemia, opiate overdose, postictal coma, sepsis, meningitis,encephalitis, uremia, metabolic abnormalities, respiratory distress,hypotension, drug-induced hepatic failure, ketoacidosis, intracranialpathology such as intracerebral hemorrhage and/or hypertension.
A notation must be recorded in the patient’s chart documenting a baselinephysical examination. A statement documenting the indications forstarting the ethanol infusion protocol.
Prior to and within six hours of the initiation of the ethanol infusion thefollowing laboratory studies will be obtained: CBC, serum electrolytes(Na, K, Cl, HCO3), BUN, Cr, glucose, iCa, Mg, phosphorous, PT/INR,LFT’s (AST, ALT). Monitoring of BAL, electrolytes and glucose will be performed at leastdaily, throughout the duration of ethanol infusion. A BAL should beobtained six hours after initiation of infusion and six hours after eachincrease in dosage.
Prophylaxis for stress gastritis, with H2-blocker or sucralfate must be initiated prior to the initiation of the ethanol infusion.
All patients will receive either oral multivitamin daily or intravenousmultivitamins three times a week. Additionally, the following adjunctivemetabolic measures should be employed: Vitamin supplementation(folate, thiamine, B12), magnesium sulfate for magnesium deficiency (Mg < 1.5mg/dL) and sodium or potassium phosphate for phosphatedeficiency (Phos < 2.7mg/dL), haloperidol for anxiety/agitation, nicotinereplacement therapy for active tobacco users: Folate 1mg, IV, qd x 3, then 1mg IV or PO qd thereafter.
Thiamine 100mg, IV, qd x 3, then 100mg IV or PO qd thereafter.
Give prior to glucose infusion.
MVI 1 amp IV, qd x 3, then 1 amp or tablet IV or PO qd thereafter. For the management of acute agitation it is recommended thatintravenous haloperidol (Haldol) be administered beginning withan initial dose for young patients of 2-5mg every four hoursaround the clock. For the elderly and medically compromised give0.5-1mg IV every four hours around the clock. For all patientsadministered IV haloperidol, obtain serum Mg and K at baseline,every 12 hours for 24 hours, then once daily. In patients withknown ventricular arrhythmias, active ischemia, significant leftventricular dysfunction, electrolyte imbalances, concurrent therapywith type 1A antiarrhythmics, or any other condition or drug knownto prolong the QT interval, obtain a baseline QTc interval andQTc interval every 24 hours thereafter. The QTc interval shouldnot be greater than 440 milliseconds at initiation of haloperidoltherapy, and should not increase by more than 15% duringhaloperidol therapy. Additional psychiatric diagnoses may co-exist in the alcohol-dependent patient and should be recognized.
Psychiatric consultation should be obtained so appropriatetherapy may be instituted in a timely fashion.
Nicotine replacement therapy (Nicoderm, 21 mg/patch, qd).
Addiction Rehabilitation Services Consultation for alcohol addictiontreatment, rehabilitation and follow-up prior to patients discharge ortransfer. Transition to an alcohol treatment and rehabilitation program,once the patient has recovered from the acute medical/surgical injury orillness.
Initiate ethanol infusion at 1cc/kg/hr (10% ethyl alcohol in D5W, NS or ½ NS), via a peripheral or central venous line 6-8 hours following admission.
If the patient’s BAL is unmeasureable at the time of the initiation of theinfusion, a loading dose equal to 0.5-1cc/kg of 10% ethyl alcohol shouldbe given. Documentation of the CIWA-Ar score should be performedevery 2-4 hours, see Appendix A. Ethanol dosage should be titrated according to the patient’s clinical
condition. Titration of the dosage is achieved by giving an initial bolus of
0.5-1.0cc/kg of 10% (or half this volume if the patient has 20% ethanol
infusing) followed by an increase in drip rate of 10-20cc/hr. Increases in
rate should not be done any more frequently than every 4 hours. One or
two additional boluses (maxiumum of two) of 0.5-1cc/kg can be given if
the patient’s clinical condition warrants additional ethanol prior to the next
allowable increase in the rate of infusion. The intent of ethanol
replacement is to attenuate the severity of AWS symptomotology and
prevent the development of delirium tremens. Most patients will develop
a low-grade fever (101-102BF) and mild tachycardia (heart rate 110-
120/minute), representing mild AWS as the patient is detoxifying. Further
increases in ethanol dose, in an attempt to normalize these vital signs,
will only lead to attaining toxic BAL’s (> 80mg%) and are therefore
discouraged. The patient’s physician should be notified if a patient
requires more than one dose adjustment per shift.
If the patient requires greater than 100 ml/hr of 10% solution, a change to20% ethyl alcohol solution in D5W should be undertaken to avoidexcessive free water administration. The 20% ethyl alcohol solution ishypertonic (~3429mOsm) and must be administered via a central line.
Patients requiring a dose exceeding 50 cc/hr of 20% ethanol should bemonitored in a step-down or ICU setting. The patient’s physician shouldbe immediately notified if any patient requires a dose in excess of 60cc/hrof 20% ethanol. No patient should receive a dose in excess of 70cc/hr of20% ethanol.
Subsequent titration of rate and concentration should maintain the patientin a calm, yet nonsedated state, based on the CIW-Ar score. Thetherapeutic goal is to achieve and maintain an individual's CIW-Ar score£10. The BAL needed to achieve this clinical endpoint is generally <20mg/dL. Once a patient is on an adequate dose, this infusion rateshould be continued for 7 days and a BAL obtained daily. At the end of 7days of therapy, the ethanol infusion is discontinued, without a taper asthe patient is now detoxified. It should be emphasized that the use of ethanol in this manner targets aclinically-based therapeutic goal and does not depend upon achieving aparticular BAL. Ideally, the BAL should remain at very low-to-undetectable levels (i.e. BAL < 20mg/dL), however rare patients mayrequire a higher BAL for control of their AWS. Patients requiring BAL’sgreater than 40mg%, should have their infusions reduced once they have responded clinically (ie CIWA-Ar score £ 10 or decrease by 5) for 24 hours to achieve a BAL <20mg% while maintaining the CIWA-Ar £10. The value of a daily BAL is to ensure the level remains at a low andstable level. The initiation dose of ethyl alcohol used here, 1cc/kg/min(0.1gm/kg/hr), is just below the level at which the metabolic capacity ofthe average person becomes saturated. Ethanol is metabolized via aliver enzyme system (following Michaelis-Menton enzyme kinetics, withsignificant variation depending upon the patient’s recent alcohol ingestionhistory).Thus a large increase in the BAL may result from a relativelysmall increase in the infusion rate, especially at rates > 1cc/kg/hr of 10%ethanol in D5W (0.1gm/kg/hr). The goal of performing daily BAL measurements is to prevent a rising BAL during “maintenance” infusion.
Individual patient responses may vary and thus require constant clinicaland laboratory monitoring throughout the duration of ethanoladministration. The patient’s physician should be immediately notified forany patient with a BAL > 50mg/dL.
After the patient has been on a stable infusion for six hours, a BAL shouldbe obtained and should be rechecked on a daily basis thereafterthroughout the duration of ethanol administration. A stable infusion rate isdefined as: a six hour period during which the patient's CIWA-Ar scoreremains unchanged or improved and there have been no changes in theethanol dose administered. If there is active titration of the ethanolinfusion then a BAL should be checked at six hours following eachchange in dosage. If the patient has a detectable BAL and has continued agitation, a promptre-evaluation for other causes of mental status changes must beperformed and the patient’s physician must be notified. At the end of 7 days of therapy, the ethanol infusion is discontinued,without a taper as the patient is now detoxified. All patients are monitoredfor evidence of withdrawal symptomotology for 72 hours thereafter if theyremain hospitalized. If the patient's medical/surgical condition is clearedfor discharge prior to the 7-10 days (i.e., still potentially alcoholdependent), then subsequent management is dictated by whether thepatient has consented to enrollment into an alcohol rehabilitation programor not. If the patient has consented to further treatment, thenarrangements will be made for alcohol addiction treatment andrehabilitation through Addiction Rehabilitation Service. If the patient hasrefused enrollment then they can be discharged with proper follow-upcare for their medical/surgical /psychiatric conditions. Pump and rate of infusion are to be monitored every two hours.
Documentation of CIWA score every two-four hours, while the infusion isbeing titrated. Once the ethanol dose is unchanged for twelve hours, thefrequency of obtaining the CIWA score can be reduced to once everyshift.
Notify physician if: a) CIWA score increased by five or more points, b)patient behavior places self or caregivers at risk, or c) any worsening ofpatient’s mental status exam.
Document all changes in ethanol dose (rate and/or concentration) inMAR.
INFUSION/MEDICATION COMPATIBILITY AND INCOMPATIBILITY:1. The 10% ethanol infusion can be administered in D5W, NS or ½ NS. The 20% ethanol infusion must be administered in D5W only.
The following have been shown to be incompatible with ethanol infusionsand cannot be administered in the same line: edetate disodium tetraacetic acid (EDTA), penicillin G, phenobarbital sodium bicarbonate,tobramycin.
Patients on any of the following medications can have potentialinteractions with ethanol infusion and should be used with caution:carbamide, chloramphenicol, chloral hydrate, nitrofurantion,phentolamine, procarbazine, quinacrine, sulfonamides and tolazoline.
Compiled by the Ad Hoc Alcohol Dependence Study Group of the Institute ofLiving and Hartford Hospital.
Vincent Cortes, M.D.
James Duffy, MDRichard Gannon, Pharm.D.
Ned Jaroszewski, MDGeorge Perdrizet, M.D.,PhD, ChairpersonPeru Venketash, MDCharles Wilber, M.Ed.
5/99, modified 9/01Therapeutics Committee Approval Date 10/1/2001Medical Executive Committee Approval Date 11/5/2001Monica Goldman, R.Ph.
Modified 11/7/2002 i Wilkinson, PK. Pharmacokinetics of Ethanol: A Review. Alcoholism: Clin ExpResearch 1980;4:6-21.
ii Wagner JG, Wilkinson PK, Sedman AJ, et al. Elimination of alcohol from humanblood. Jor Pharm Sci 1976;152-154.


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