15 tratamiento alcoholismo

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MEDICINE 34:8 323 © 2006 Elsevier Ltd. All rights reserved.

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Allister Vale

Allister Vale MD FRCP FRCPE FRCPG FFOM FAACT FBTS Consultant Clinical Pharmacologist and Director ofthe National Poisons Information Service (Birmingham Centre) and West Midlands Poisons Unit,City Hospital, Birmingham, UK. He is a Past-President of the British Toxicology Society and ofthe European Association of Poisons Centres and Clinical Toxicologists, and a former Trustee ofthe American Academy of Clinical Toxicology.

The alcohol withdrawal syndrome is acommon medical problem. In one studyfrom Australia, 8% of 2000 randomlyselected hospital in-patients were consid-ered to be at risk of alcohol withdrawal. 1 The syndrome is characterized by auto-nomic hyperactivity, tremor, anxiety andrestlessness and is occasionally compli-cated by seizures, hallucinations anddelirium. It follows the abrupt discontinu-ation of, or at least the rapid decrease inintake of, alcohol after heavy and pro-longed use.

The DSM-IV diagnostic criteria foralcohol withdrawal are met when two ormore of the following are present:• autonomic hyperactivity (e.g. sweating

or pulse rate greater than 100 bpm)• increased hand tremor• insomnia• nausea or vomiting• transient visual, tactile or auditory hal-

lucinations or illusions• psychomotor agitation• anxiety• grand mal seizures. 2

The syndrome occurs within hours ofalcohol cessation or reduction, thoughalcohol withdrawal delirium does not usu-ally develop for 2–3 days after cessationof drinking and usually lasts for 48–72hours. In the past, the mortality of alcohol

withdrawal was high, often as much as15%, 3 but with advances in recognitionand treatment, more recent studies indi-cate a mortality of 2%, 4 although 8% ofthose who developed delirium died. 4

The alcohol withdrawal syndromemay develop in patients admitted to hos-pital for an unrelated illness (e.g. for anoperation) or patients may present in aconfused state to the Emergency Depart-ment due to the onset of the syndrome.In both these circumstances, which aremedical emergencies, the diagnosis is

often delayed as it is not considered. Theimmediate input of medical and nursingstaff experienced in the management ofalcohol withdrawal is a necessity.

In addition, patients may be referredby their GP specically for ‘detoxica-tion’. Such a referral is often precipitatedby the patient's family rather than a realdesire by the patient to ‘come off’ alco-hol and many such patients present foradmission after ‘one last binge’. How-ever, for patients who lack commitmentto discontinue alcohol long-term and who

are under great pressure from their familyto do so, detoxication is rarely by itself avery effective way of helping a patient. Inaddition, some alcohol abusers with littlefamily or other support regard withdrawalas a convenient way of commencing the

next drinking bout in good health aftera period of pleasant food, shelter andcompany in hospital.

Hence, before arrangements for detox-ication are made, goal setting is impor-tant and the purpose of treatment shouldbe stated explicitly. The following ques-tions should be considered.• Is the patient committed to discontinu-ing alcohol permanently?• What are the patient's expectations ofthe treatment?• What are the relatives' expectations?

• What are the GP's expectations?• Is the family/GP more committed thanthe patient?

Out-patient treatment is possible forsome of these patients, particularly if thepatient is committed and has discontinuedalcohol for more than two days previouslywithout major adverse effects. Out-patienttherapy is unlikely to be appropriate ifthere is a history of severe withdrawaland/or withdrawal seizures, there is anunsupportive home environment or littlecommunity health care support, or a pre-

vious failed community detoxication.

Mechanisms of alcohol withdrawal

The mechanisms underlying the alcohol with-drawal syndrome include a reduced activityof the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), enhanced activ-ity of the excitatory transmitter glutamateand reduced dopamine release. 5–8

While alcohol enhances the effect ofGABA on GABA-A neuroreceptors, result-ing in decreased overall brain excitability,

The management of alcoholwithdrawal



WHAT'S NEW IN THE MANAGEMENT OF ALCOHOL WITHDRAWAL


chronic use results in a compensa-tory decrease of GABA-A neuroreceptorresponse to GABA, evidenced by increas-ing tolerance to the effects of alcohol. 5 Withthe onset of alcohol withdrawal, there is asudden relative deciency in GABA neu-rotransmitter activity, which is believed to

contribute to the anxiety, increased psy-chomotor activity and seizures observed.Conversely, alcohol inhibits glutamate

receptors (N-methyl-D-aspartate, NMDAreceptors) and chronic alcohol use resultsin up-regulation of these receptors so thatmore alcohol is required to achieve recep-tor inhibition. 6 Abrupt cessation of alcoholexposure results in brain hyperexcitabilityas glutamate inhibition is removed. Brainhyperexcitability manifests clinically asanxiety, irritability, agitation, tremors andwithdrawal seizures.

In addition, signicant increases inplasma norepinephrine have been found,at least for the rst 24 hours after ces-sation of alcohol with signicant downregulation of the α2 receptor, which con-tribute to the autonomic features. 9

Features of alcohol withdrawal

The common features of withdrawal areshown in Table 1 . Foy et al .10 studied 539episodes of alcohol withdrawal, of which90 related to patients with a primary

diagnosis of alcohol intoxication or with-drawal. Sixty-eight patients were admittedwith seizures, 19 with hallucinations and31 with delirium. Nine patients had bothdelirium and seizures on admission. Six-teen of the seizures were known to be dueto a cause other than alcohol withdrawaland 14 were of unclear aetiology. Thus,

79 patients had a denite complication ofalcohol on admission. After admission,113 patients had complications of alcoholwithdrawal in the form of seizures, hal-lucinations or delirium; 17 of these alsohad complications on admission. Twopatients died during the period of alcohol

withdrawal.There is only a general relationshipbetween the duration of alcohol abuseand the severity of withdrawal. Varia-tion in severity occurs even in the samepatient from one withdrawal episode tothe next. If there is a past history of sei-zures and delirium tremens during with-drawal, these features are more likely tooccur in the next withdrawal episode. Inaddition, the impact of concurrent illnessand infection must be considered, as wellas simultaneous withdrawal from other

drugs.

Use of an assessment tool

Patients will often complain of withdrawalsymptoms but have no objective evidenceof withdrawal. Objective assessment istherefore mandatory. Careful monitoring(hourly in severe cases) using the revisedClinical Institute Withdrawal Assessmentfor Alcohol (CIWA-Ar) score ( Table 2 ) willensure that any change in the severity ofwithdrawal is identied at the earliest pos-

sible time. The revised and shortened scaleis a validated 10-item assessment tool thathas been demonstrated to have high reli-ability, reproducibility and validity basedon comparisons with ratings by experi-enced clinicians. In practice, the scale issimple to use and can be employed notonly to quantify the severity of the alcohol

withdrawal syndrome but to medicatepatients going through withdrawal, partic-ularly if the symptom-triggered approach isadopted. It has been proposed that a scoreof 9 or less indicates mild withdrawal, ascore of 10 to 18 indicates moderate with-drawal and a score of 18 or above suggests

severe withdrawal.11

Management

Owens et al .12 have shown that even in2003 only 17.6% of UK hospitals had carepathways for the pharmacological andnon-pharmacological treatment of patientssuffering from alcohol withdrawal.The aims of detoxication are to:• provide safe withdrawal from alcohol

and enable the patient to become alco-hol free

• provide withdrawal that is humane,thus protecting the patient's dignity

• prepare the patient for ongoing treat-ment for their dependence on alcohol.

It is essential that nursing staff are pres-ent in sufcient numbers to monitorpatients carefully and to prevent themsuffering injury while confused. Constantassessment and support by staff and goodlighting at night are essential to providereassurance and a favourable outcome.

Is drug treatment required?

Patients requesting (even demanding)their preferred withdrawal medication inhigh dose on admission should be resisted.It is irrational to prescribe drugs for with-drawal if only minor features are present.In one study, 1024 patients with alcoholwithdrawal (47% had a mild tachycardia,37% tremulousness, 37% vomiting, 53%anorexia, 4% hallucinations, 1% seizures)were treated without medication. 13 Thisapproach offers several advantages. Firstly,patients with no or only mild symptomsare not obtunded by the routine use of

drugs such as benzodiazepines. Secondly,the period of detoxication is shorterand, thirdly, alcohol abusers learn how toexercise immediate non-pharmacologicalcontrol over their life.

Fixed schedule or symptom-triggeredregimens?If drug treatment is required, patientsshould be treated with regimens that arepatient specic and exible to respond tochanges in severity of withdrawal (symp-tom-triggered). Fixed treatment schedules,

Features of the alcohol withdrawal syndrome

• Tremor of extended hands, tongue or eyelids

• Sweating• Nausea and/or vomiting• Sinus tachycardia• Psychomotor agitation• Insomnia• Anxiety• Headache• Fever • Decreased attention• Disorientation• Clouding of consciousness

Table 1




Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale

Patient …………………………………… Date …………….… Time …………… Pulse or heart rate (taken for 1 min) …………………… Blood pressure …………NAUSEA AND VOMITING – 'Do you feel sick to your stomach?Have you vomited?'0 – No nausea and no vomiting1 – Mild nausea with no vomiting234 – Intermittent nausea with dry heaves567 – Constant nausea, frequent dry heaves and vomiting

VISUAL DISTURBANCES – 'Does the light appear to be too bright? Is itscolour different? Does it hurt your eyes? Are you seeing anything that isdisturbing to you? Are you seeing things you know are not there?'0 – Not present1 – Very mild sensitivity2 – Mild sensitivity3 – Moderate sensitivity4 – Moderately severe hallucinations5 – Severe hallucinations6 – Extremely severe hallucinations7 – Continuous hallucinations

TREMOR – Arms extended and ngers spread apart0 – No tremor 1 – Not visible, but can be felt ngertip to ngertip234 – Moderate, with patient's arms extended567 – Severe, even with arms extended

TACTILE DISTURBANCES – 'Have you any itching, pins and needles,burning, numbness? Do you feel bugs crawling on or under your skin?'0 – None1 – Very mild itching, pins and needles, burning or numbness2 – Mild itching, pins and needles, burning or numbness3 – Moderate itching, pins and needles, burning or numbness4 – Moderately severe hallucinations5 – Severe hallucinations6 – Extremely severe hallucinations7 – Continuous hallucinations

PAROXYSMAL SWEATS0 – No sweat visible1 – Barely perceptible sweating, palms moist234 – Beads of sweat on forehead567 – Drenching sweats

AUDITORY DISTURBANCES – 'Are you more aware of sounds? Arethey harsh? Do they frighten you? Are you hearing anything that isdisturbing? Are you hearing things you know aren't there?'0 – Not present1 – Very mild harshness or ability to frighten2 – Mild harshness or ability to frighten3 – Moderate harshness or ability to frighten4 – Moderately severe hallucinations5 – Severe hallucinations6 – Extremely severe hallucinations

7 – Continuous hallucinationsANXIETY – 'Do you feel nervous?'0 – No anxiety, at ease1 – Mildly anxious234 – Moderately anxious, or guarded, so anxiety is inferred567 – Equivalent to acute panic states as seen in severe delirium or

acute schizophrenic reactions

HEADACHE, FULLNESS IN THE HEAD – 'Does your head feel different?Does it feel like there is a band around it?' (Do not rate for dizzinessor lightheadedness; otherwise, rate severity)0 – Not present1 – Very mild2 – Mild3 – Moderate4 – Moderately severe5 – Severe6 – Very severe7 – Extremely severe

AGITATION

0 – Normal activity1 – Somewhat more than normal activity234 – Moderately dgety and restless567 – Paces back and forth during most of the interview, or constantly

thrashes about

ORIENTATION AND CLOUDING OF SENSORIUM – 'What day is this?

Where are you? Who am I?'0 – Oriented and can do serial additions1 – Cannot do serial additions or is uncertain about date2 – Disoriented for date by no more than 2 calender days3 – Disoriented for date by more than 2 calender days4 – Disoriented for place and/or person

Total CIWA-Ar Score .............................. Rater's name .................................................Available at: www.asam.org/Addiction%20Medicine%20Essentials/INSERT%20jan-feb%202001.pdf

Table 2





where the patient is given a standard regi-men irrespective of their symptoms, areinappropriate.

Saitz et al .14 reported the clinical coursein 101 inpatients in a detoxication unitwho were randomized to receive eithera xed-schedule regimen (n = 50) or a

symptom-triggered regimen (n = 51). Thexed-schedule regimen involved the admin-istration of chlordiazepoxide every sixhours for 12 doses (50 mg × 4; 25 mg × 8)plus additional medication (chlordiaz-epoxide 25–100 mg hourly) as required(CIWA-Ar score ≥8). The symptom-trig-gered regimen involved the administra-tion of chlordiazepoxide 25–100 mg hourly(CIWA-Ar score ≥8). In addition, patientsin this group received an identical placeboevery 8 hours for 12 doses. The outcome isshown in Table 3 from which it is clear that

a symptom-triggered approach decreasesboth treatment duration and the amount ofbenzodiazepine used. Similar results havebeen reported by others. 15,16

When to treat Following a meta-analysis, the AmericanSociety of Addiction Medicine producedan evidence-based Practice Guideline thatrecommended that treatment should beinitiated using a symptom-triggered regi-men when the CIWA-Ar score is >8; thiswill benet the patient symptomatically. 17

When the CIWA-Ar score is ≥15 the use ofa symptom-triggered regimen reduces therisk of major complications developing. 17

Which drug?Benzodiazepines: a meta-analysis com-paring benzodiazepines with placeboshowed that benzodiazepines were moreeffective than placebo in reducing thesigns and symptoms of alcohol with-drawal and were more effective thanplacebo in reducing the incidence of sei-zures and delirium. 17,18 Trials comparing

different benzodiazepines demonstratedthat all appear similarly efcacious inreducing signs and symptoms of with-drawal. However, there is some evidencethat longer-acting benzodiazepines (e.g.diazepam) may be more effective in pre-venting seizures 17 and may produce asmoother withdrawal course with lessbreak-through or rebound symptoms thanshorter-acting agents. Benzodiazepineswith a rapid onset of action may have ahigher abuse potential than those withslower onset of action.

If possible, diazepam should be admin-istered orally in doses of 10–20 mg usinga symptom triggered regimen. In severecases of withdrawal, substantial doses willneed to be given to control the features.If oral therapy is not possible, boluses ofintravenous diazepam 10–20 mg should

be given to control features; umazenilshould be readily available in the event ofrespiratory depression being induced.

Other sedative–hypnotic drugs: pro-spective controlled trials indicate thatclomethiazole is better than placebo inreducing symptoms of withdrawal andthat barbital is equal to benzodiazepinesin this regard. 17 There are insufcientdata to draw conclusions on preventingseizures 17 and delirium 18 in the case ofclomethiazole, but barbital appears to be

of similar efcacy to benzodiazepines intreating delirium. No adequate controlledtrials on phenobarbital could be identi-ed, but uncontrolled studies suggest thatphenobarbital is likely to be of similarefcacy to barbital. However, both barbi-tal and phenobarbital have a lower safetyprole than benzodiazepines, particularlywhen used in high doses. Moreover, incontrast to the benzodiazepines, no spe-cic antidote is available if respiratorydepression supervenes following the useof barbital or phenobarbital.

Neuroleptics (phenothiazines and halo-peridol): there is some evidence thatphenothiazines and haloperidol aloneare effective in reducing features of with-drawal, but they are less effective than ben-zodiazepines and other sedative–hypnoticdrugs in treating delirium. 17,18 In addition,they increase the incidence of seizurescompared to placebo and are less effectivethan benzodiazepines in preventing sei-zures. 17 Nonetheless, clinical experienceand published data suggest that neuro-

leptic agents, such as haloperidol 5 mg by

intravenous or intramuscular injections,repeated once as appropriate, may be veryeffective in diminishing features of severewithdrawal and delirium (notably agita-tion, perceptual disturbances, or disturbedthinking) in patients who have alreadyreceived substantial amounts of a ben-

zodiazepine and whose features remainuncontrolled. 18

β-adrenoceptor blocking drugs: there issome evidence that β-adrenoceptor block-ing drugs reduce the autonomic featuresof withdrawal, 17 though they have noanticonvulsant activity. The effect of β-adrenoceptor blocking drugs on deliriumhas not been investigated, but these drugsare known to cause delirium.

Carbamazepine has been shown to be

superior to placebo in treating patientswith mild-to-moderate withdrawal; it isof similar efcacy as barbital. 17

Clonidine: well-designed studies haveshown that clonidine is effective in ame-liorating the features of mild-to-moderatewithdrawal. 17 No data on the efcacyof clonidine in preventing seizures andtreating delirium are available. 17

Thiamine: alcohol dependent individu-als are often thiamine decient. Thiamine

prevents Wernicke's encephalopathy andKorsakoff's psychosis and should there-fore be administered to all such patients onadmission, unless Wernicke's encephalop-athy or Korsakoff's psychosis is suspected(when parenteral administration of B vita-mins is appropriate e.g. Pabrinex® [Linkpharmaceuticals] high potency injectionintravenously over 10 minutes), oral thia-mine 100 mg bd should be given as poten-tially serious allergic adverse reactions mayoccur during, or shortly after, administra-tion of the parenteral preparation. Thia-

mine does not reduce delirium or seizures.

Fixed schedule or symptom-triggered regimens

Outcome Fixed schedule (n = 50) Symptom-triggered (n = 51)

Treatment duration (hour) 68 (64–73) 9 (0–43)*Chlodiazepoxide (mg) 425 (350–750) 100 (0–400)*Hallucinations (%) 4 2Delirium tremens (%) 6 2

*p < 0.001

Table 3





Conclusions

• A symptom-triggered regimen is best.• Benzodiazepines are the agents of rstchoice as they have better documentedefcacy, a greater margin of safety and alower abuse potential.• Diazepam is a long-acting benzodi-azepine and is modestly priced. It may begiven intravenously, if necessary, thoughthe oral route is preferred if the patientis able to comply with an oral regimen.Diazepam should be administered using asymptom-triggered regimen.• In those patients who are still manifest-ing the signs of severe withdrawal despiteappropriate doses of diazepam, haloperi-dol 5 mg intravenously or intramuscularlyshould be administered, repeated once, asappropriate.• All patients should receive thiamine100 mg bd orally, unless Wernicke'sencephalopathy or Korsakoff's psychosisis suspected, when parenteral administra-tion of B vitamins is appropriate. ◆

REFERENCES1 Foy A, Kay J. The incidence of alcohol-

related problems and the risk of alcoholwithdrawal in a general hospital population.Drug Alcohol Rev 1995; 14: 49–54.

2 American Psychiatric Association.

Diagnostic and statistical manual ofmental disorders. 4th edn. Washington,DC: American Psychiatric Association;1994.

3 Victor M, Adams R D. The effect ofalcohol on the nervous system. ResPubl Assoc Res Nerv Ment Dis 1953; 32:526–73.

4 Ferguson J A, Suelzer C J, Eckert G J, ZhouX H, Dittus R S. Risk factors for deliriumtremens development. J Gen Intern Med

1996; 11: 410–4.5 Davis K M, Wu J-Y. Role of glutamatergicand GABAergic systems in alcoholism.

J Biomed Sci 2001; 8: 7–19.6 Tsai G, Coyle J T. The role of glutamatergic

neurotransmission in the pathophysiologyof alcoholism. Annu Rev Med 1998; 49:173–84.

7 Littleton J. Neurochemical mechanismsunderlying alcohol withdrawal. AlcoholHealth Res World 1998; 22: 13–24.

8 Laine T P, Ahonen A, Torniainen Pet al. Dopamine transporters increase in

human brain after alcohol withdrawal. MolPsychiatry 1999; 4: 189–91.

9 Smith A J, Brent P J, Henry D A, Foy A.Plasma noradrenaline, platelet alpha2-adrenoceptors, and functional scoresduring ethanol withdrawal. Alcohol ClinExp Res 1990; 14: 497–502.

10 Foy A, Kay J, Taylor A. The course ofalcohol wthdrawal in a general hospital.Q J Med 1997; 90: 253–61.

11 Mayo-Smith M F. Management of alcoholintoxication and withdrawal. In: Graham AW, Schultz T K, Mayo-Smith M F, Ries R K,

Wilford B W, eds. Principles of addictionmedicine. Chevy Chase . Maryland:American Society of Addiction Medicine;2003: 621–31.

12 Owens L, Gilmore I T, Pirmohamed M.How do NHS general hospitals in Englanddeal with patients with alcohol-relatedproblems? A questionnaire survey. Alcohol 2005; 40: 409–12.

13 Whiteld C L, Thompson G, Lamb A,Spencer V, Pfeifer M, Browning-Ferrando

M. Detoxication of 1024 alcoholicpatients without psychoactive drugs. JAMA 1978; 239: 1409–10.

14 Saitz R, Mayo-Smith M F, Roberts M S,Redmond H A, Bernard D R, Calkins D R.Individualized treatment for alcoholwithdrawal: randomized double-blindcontrolled trial. JAMA 1994; 272:519–23.

15 Hardern R D, Page A V. An audit ofsymptom triggered chlordiazepoxidetreatment of alcohol withdrawal on amedical admissions unit. Emerg Med J

2005; 22: 805–6.16 Daeppen J-B, Gache P, Landry U et al.

Symptom-triggered vs xed-scheduledoses of benzodiazepine for alcoholwithdrawal - a randomized treatmenttrial. Arch Intern Med 2002; 162:1117–21.

17 Mayo-Smith M F, Cushman Jr P, Hill A Jet al. Pharmacological managementof alcohol withdrawal: a meta-analysisand evidence-based practice guideline.

JAMA 1997; 278: 144–51.18 Mayo-Smith M F, Beecher L H, Fischer T L

et al. Management of alcohol withdrawaldelirium: an evidence-based practiceguideline. Arch Intern Med 2004; 164:1405–12.

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