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Home , Alcohol intoxication, Delirium tremens

• tremens: A review

RICHARD E. GRIFFIN, DO GEORGE A. GROSS, DO, MPH HOWARD S. TEITELBAUM, DO, PhD, MPH

Delirium tremens was first iden­ The biblical comments had to do with the tified as being due to long-term excessive observed behavior of the drinker and the effect of intake in 1813, but is now known to heavy drinking: 'Who hath woe? .. sorrow? ..con­ be associated with abrupt withdrawal of tentions? .. redness of eyes? .. They that tarry long alcohol in chronically habituated persons. at the ." (Proverbs 23:20-21). It is not known Recent publications quote an anticipated if the withdrawal syndrome was common or rec­ mortality rate of 15% to 20%. Our experience ognized as a result of excessive drinking; howev­ in the past 20 years has not confirmed that er, the verse in Proverbs 23:32, "At the last it rate. This review reveals that the prevalence biteth like a serpent, and stingeth like an adder," of fatal cases is extremely low, with the true could be a reference to some observed central ner­ mortality close to 0%. We believe that this vous system (CNS) symptoms such as , decrement is due to the increasing use of in withdrawal. to detoxify alcoholic patients. More recently alcohol is being recognized as It is posstulated that the benzodiazepines a major etiologic factor in the of young peo­ act either to prevent or to ple (motor vehicle accidents), as well as in dis­ reduce the disruption in eases of various organ systems. Excessive use of alco­ the central nervous system caused by exces­ hol has been implicated in the development of sive alcohol intake, or both. malignancies, particularly of the gastrointestinal (Key words: Electrolytes, mortality rate, tract. 1 Studies of revealed that alcohol alcohol withdrawal syndrome, benzodi­ could kill if consumed in too great a quantity, but azepines, , and alcohol ) also seemingly when the drinker decreased or ceased its consumption. Acute treatment of alco­ Alcohol and drinking to excess have been a holism has been directed at detoxification and the part of human culture since the beginnings of civ­ withdrawal syndromes, in particular, the potentially ilization. Comments on drinking appear in the fatal condition delirium tremens. . Morning drinking and drinking through­ According to the National Institute of Drug out the day, 'Woe unto them that rise up early in Abuse's 1990 National Household Survey on Drug the morning, that they may follow strong drink; that Abuse, there are 102.9 million people in the Unit­ continue until night, till wine inflame them" (Isa­ ed States who use alcohol. The lifetime prevalence iah 5:11), was recognized as being different than of alcoholism among all drinkers is 15.4%, of whom social drinking, " ... but use a little wine for thy 2.5% can be expected to experience severe withdrawal. stomach's sake and thine often limitations." (1 The mortality attributed to delirium tremens is Timothy 5:23). usually quoted as being as high as 20%,2 which suggests that we could expect 79,233 deaths per year Drs Griffin, Gross, and Teitelbaum are professors at Michi­ from delirium tremens. This rate would place delir­ gan State University, Department of Community Health ium tremens among the top 10 causes of in Sciences, East Lansing, Mich. Correspondence to Richard E. Griffin, DO, Department the . It is not so listed. Chronic of Community Health Sciences, B522 East Lansing, MI and accounted for 24,820 deaths 48824-1316. in the 12 months ending November 1991, giving

924 • JAOA • Vol 93 • No 9 · September 1993 Review article • Griffin et al Table 1 Relation of Delirium Tremens to Cessation of Drinking: An Analysis of 101 Cases

Related variable Time of Time of onset after onset after last drink hospitalization Indeterminate Interval, No. of No. of No. of h cases cases cases

~24 2 4 ... 25-48 11 15 . .. 49-72 7 4 ...

73-96 17 6 ... > 96 7 2 ... -- -- TOTAL 44 31 26

Adapted from Victor and Adams.6 a rate of 9.8 per 100,000.3 In the United States, Delirium tremens is characterized by the fol­ these were primarily due to . lowing: (1) elevated temperature (100.2°F); (2) In our own experience in treating alcoholic (90 beats per minute); (3) elevated patients (19 years averaging 700 admissions per blood pressure (140/90) mm Hg; (4) tremulous­ year), we have seen two persons in alcohol with­ ness; (5) diaphoresis; (6) ; (7) dis­ drawal who appeared to be suffering from deliri­ orientation; (8) (9) agitation; um tremens. Both recovered. The incidence of and (10) inability to feed oneself.6-8 delirium tremens would be 1.5 per 100,000 in this informal survey. Colleagues have reported similar Historical perspective expenences. Delirium tremens was first described in the med­ icalliterature in 1813 by Thomas Sutton.9 He CUlTent diagnostic criteria identified excessive intake of alcohol for a long The criteria for alcohol withdrawal delirium, accord­ period as the etiologic agent. He differentiated ing to the Diagnostic and Statistical Manual ofMen­ delirium tremens from "phrenitis" (inflammation tal Disorders (DSM-III-R), 4 are as follows: (1) Delir­ of the brain) by noting that delirium tremens had ium. .,developing after cessation of heavy alcohol a prodrome of , fever, and diaphoresis. Sut­ ingestion or a reduction in the amount of alcohol ton described a syndrome of malaise, headache, ingested (usually within 1 week); (2) marked auto­ fever, tremor, general agitation, , forget­ nomic hyperactivity, such as tachycardia, sweating; fulness, tetany, and diaphoresis. He treated delir­ (3) not due to any other physical or . ium tremens with with good results. He These foregoing criteria reflect a psychiatric noted 2 deaths in 16 cases so treated (12.5% mor­ bias. The consensus of people working in the field tality rate). of medicine reflects the results of phys­ According to Romano,lO Ware described the ical examination of the alcoholic in addition to a psy­ clinical manifestations of delirium tremens in chiatric evaluation. A consensus definition of delir­ 1831, his diagnosis resting on the presence of ium tremens is a syndrome that follows a long "... delirium, watchfulness, and tremor." He thought period of heavy drinking, occurring within 3 to 5 that these manifestations were due to drinking, days following the cessation of alcohol ingestion and dismissed sudden abstinence as a cause. Ware (Tables 1 and 2). Delirium tremens is usually pre­ did not think that any treatment was necessary in ceded by a prodromal syndrome.5 the person who was in good health; in others, he (Continued on page 929)

Review article • Griffin et al JAOA • Vol 93 • No 9 • September 1993 • 925 Table 2 Mortality in Delirium Tremens: Review of the Literature

Prevalence No. of of cases No. of cases with deaths No. of with delirium from Mortality alcoholic delirium tremens delirium rate Authority Year cases tremens (%) tremens (%) I Sutton9 1813 16 16 100.0 2 12.5 Bostonll 1908 Not cited 140 Undetermined 1-13 0-70.0

Ranson and ScoW4 1911 Not cited 934 Undetermined 206 37.0 Hoppe15 1918 375 59 15.7 2 3.4

Cline and Coleman16 1936 Not cited 157 Undetermined 6 3.8 Piker and Cohn 17 1937 Not cited 300 Undetermined Not cited 5.3 Moore and 1915- 38,376 2,375 6.2 560 24.0 Gray 18 1936

Victor7 1953 Not cited 101 Undetermined 15 6.7 Isbell et a}19 1955 10 2 20.0 0 0 Mendelson 1959 Not cited 30 Undetermined 0 0 et al20

Tavel et al21 1961 Not cited 162 Undetermined 30 18.5 Tavel et aP1 1961 Not cited 168 Undetermined 9 5.4 Cheshmedjiev 1972 1,156 1 0.1 0 0 and Atanassov22

Wadstein and 1978 Not cited 26 Undetermined 0 0 Skude23

Cushman24 1987 7,084 92 1.3 3 3.3

thought that bleeding would be appropriate. the cause of delirium tremens was not universal­ By 1905, there seemed to be general agree­ ly accepted. Early reports imply that the cause ment about the diagnosis of delirium tremens.ll The was the intake of alcohol. 18 As time went on, disease had been divided into two phases, with attempts were made to correlate the amounts the first, the incipient stage, characterized by ingested and the duration of the drinking with "insomnia, restlessness, tremor, and occasionally the likelihood of delirium tremens. No consistently by hallucinations."12 The second stage was char­ strong association was found. From a review of acterized by visual hallucinations, fear, boister­ the earlier literature, one might conclude that ousness, uncoordinated movements, delirium, delirium tremens was caused by chronic heavy fever, leukocytosis, and diaphoresis. drinking. Around the turn ofthe century, the Euro­ From the turn of the century until about the peans postulated that a toxin formed in the gas­ time of , 13 the incidence and prevalence trointestinal tract, kidneys, eNS, or spinal fluid (or of delirium tremens reported in the literature a combination) led to delirium tremens. 25 increased.7,9,14-24 There was no uniform definition Withdrawal of alcohol as a cause of delirium of delirium tremens during this period. tremens was met with skepticism. Bleuler,26 in Abrupt cessation of alcohol consumption as his Textbook on in 1924 said, "The

Review article • Griffin et al JAOA • Vol 93 • No 9 • September 1993 • 929 omission of alcohol kills nobody, it is only the use the ability to suppress antidiuretic hormone, so of it that does." A number of reports in the 1920s levels rise and an isosmotic retention of water and and early 1930s that examined persons who had electrolytes results. If the intake of alcohol increas­ their alcohol intake abruptly discontinued did not es, excess water and electrolytes are excreted find any marked increase in the incidence of delir­ immediately. If ingestion of alcohol ceases, the ium tremens. These reports made the point that excess water will be excreted over the course of because delirium tremens did not result from with­ several days. drawal, the practice of using alcohol as therapy Electrolyte levels below the normal range are made little . more common in alcoholic patients with associat­ It was not until 1955 that the World Health ed medical problems. Low levels of sodium have been Organization27 officially linked delirium tremens implicated in delirium tremens. Treatment with cor­ to the abrupt withdrawal of alcohol. Isbell and ticotropin7 to retain sodium at one time was rec­ ooauthors19 in the same year demonstrated that delir­ ommended; however, this therapy now seems coun­ ium tremens did not occur in persons who were terproductive, as discussed later. maintained on alcohol. As late as 1972, however, Reduced levels of magnesium28 have received researchers were publishing reports and specu- much attention as the cause of delirium tremens. 1ating on causes other than withdrawal for delir­ F1ink and coworkers29 stratified patients into three ium tremens. Cheshmedjiev and Atanassov22 categories of withdrawal: mild, moderately severe, thought that delirium tremens was probably due and severe. They tried to correlate the mean mag­ to some associated cause. They quoted Strelchuk, nesium level with the symptoms they observed in who studied 40,000 alcoholic patients and "... did their patients. The mean levels of the three with­ not find a link between abstinence and alcoholic delir­ drawal categories were not significantly different ium." Victor and Adams'4 data seem to show that and there was considerable overlap. They gave abstinence is a strong contributing factor in the varying amounts of magnesium and observed the occurrence of delirium tremens (Table 1). ' level of tremor. In a control group of nondrinkers The evidence in the literature as well as our own who demonstrated tremor, there was improve­ experience indicates the following: (1) delirium ment with administration of magnesium. Their tremens does not occur in persons whose blood conclusion was that low levels of magnesium are alcohol level is steady or rising; and (2) delirium the cause of delirium tremens. However, others tremens is seen only in persons with chronic alco­ have found that free fatty acids are elevated in holism whose blood alcohol level either is rapidly withdrawal. These bind magnesium and make it falling or has reached zero. Therefore, delirium unavailable. This factor could explain the occurrence tremens is caused by the abrupt withdrawal of of delirium tremens in patients with normal lev­ alcohol in persons who are chronically habituated els of magnesium. Administering magnesium when to the drug. free fatty acids are elevated would bind magne­ sium and therefore not relieve the symptoms.29 Biochemical abnormalities F1ink and associates29 do not mention if other med­ Investigators who studied persons suffering from ications that might have relieved the symptoms delirium tremens observed that many of them had of delirium tremens were used besides magne­ biochemical and fluid balance abnormalities. In sium. the early part of this century, delirium tremens Others also found that persons with delirium was thought to result from the cerebral edema tremens had low levels of magnesium. Wacker found at autopsy of those who, died in delirium and Vallee28 thought the low levels were due to tremens.14 Treatment included the removal of cere­ liver impairment and that raising the level of mag­ brospinal fluid. Later, delirium tremens was thought nesium would terminate delirium tremens because to be due to the dehydration caused by alcohol. 14 of its effect. They admit that some patients Most recently, the cause suggested is overhydra­ recovered from delirium tremens before a rise in tion caused by the antidiuretic effect of alcohol. magnesium level could be demonstrated. Mendel­ The immediate effect of drinking alcohol is to son and associates20 found that hallucinations induce a diuresis of water containing insignificant were slightly more frequent in those with the low­ amounts of electrolytes. The alcohol suppresses est levels of magnesium; a correlation between the release of antidiuretic hormone. Over time, if magnesium level and delirium tremens was not one assumes a homeostatic state between alcohol found. They postulated that the low magnesium level ingestion and , alcohol seems to lose was due to the diaphoresis accompanying with-

930· JAOA· Vol 93· No 9· September 1993 Review article • Griffin et al drawal, sweat concentrations of magnesium being the study to 11 the last 2 years, in which there relatively high. They also discounted low intake as were an estimated 900 admissions for alcohol a cause of the deficiency. Meyer and Urban,30 in a dependency or abuse. Of the 121 presumed cases study of 70 alcoholic persons, 45 with convulsions, of delirium tremens, 92 had documentation ade­ found low levels of electrolytes including magne­ quate enough so that the diagnosis could be made sium; they thought that the underlying mecha­ with a degree of certainty. nism was alkalosis that caused a shift of magne­ sium intracellularly. Martin and coworkers31 found Dual addiction hypomagnesemia in their patients but could not cor­ The 1985 National Household Survey on Drug relate the level with clinical findings. Others have Abuse estimated that 9 million persons had used not been able to find a correlation between mag­ both alcohol and cocaine in the previous year. nesium levels and withdrawal symptoms. Delusional disorders are common with cocaine The consensus today is that low magnesium lev­ and the effects of cocaethylene on the central ner­ els are not the sole cause of delirium tremens.32 vous system, well known. Dual addiction should For the most part, whether magnesium is imme­ increase the prevalence of delirium tremens in diately replaced in electrolyte solutions or over alcoholic persons, but this is not the case. Hypothe­ time via diet, the incidence of delirium tremens ses advanced to explain this observation are as is not affected. Embry and Lippmann,33 in 1987, follows: however, found that replacing magnesium seemed • CNS causes delirium tremens. to decrease the severity of the withdrawal, allow Alcohol decreases glucose utilization by the reduction of the dosage necessary CNS, whereas cocaine increases its use of glu­ to manage the withdrawal; and shorten the length cose. In withdrawal, the opposite occurS.35 of hospital stay. Magnesium deficiency can inter­ • Low cortisol levels cause delirium tremens. Cor­ fere with the action of and thus may be tisollevels drop rapidly to a low point on the a factor in the production of Wernicke-Korsakoff third day after no drinking. Corticotropin syndrome. increases in withdrawal. Cocaine mildly depress­ Other explanations of the causes of delirium es short term, then gradually increases corti­ tremens have included low potassium levels. Wad­ sol levels. stein and Skude23 were able to correlate decreas­ • Delirium tremens is caused by increased nor­ ing potassium levels with an increased incidence epinephrine levels. Alcohol withdrawal increas­ of delirium tremens. They thought that the decreas­ es norepinephrine. Cocaine reduces norepi­ ing level of potassium could be used as a prog­ nephrine precursors, tyrosine and phenylalanine, nostic sign of impending delirium tremens. The as well as increasing dopamine, which reduces mechanism of the onset of delirium tremens was firing of noradrenergic cells and norepinephrine thought to be increased intracellular potassium. :Knott release. and Beard34 also found decreased potassium lev­ • Serotonin depletion causes delirium tremens. els in alcoholic withdrawaL The potassium was Cocaine inhibits the reuptake of serotonin. not lost but pumped intracellularly. Vetter and Increased serotonin in synapse produces drowsi­ associates5 found no evidence that hypokalemia ness, inhibition of aggression, and impulsivi­ was responsible for delirium tremens. ty. Alcoholic persons have impaired gluconeoge­ • Disruption of in the CNS nesis secondary to the alcohol-induced redox change. causes delirium tremens. Alcohol decreases "'1- Hypoglycemia has been postulated as a cause of delir­ aminobutyric acid (GABA) in withdrawal. ium tremens, but no clear evidence of an associa­ Increasing GABA agonists increases excitabil­ tion has been produced.35 ity, and thus produces delirium tremens. This consequence can be prevented by treatment Prevalence with benzodiazepines. Table 2 demonstrates the declining prevalence of delirium tremens since Sutton first described it. An Treatment and mortality exception is Cushman24 in a retrospective study cov­ Appropriate treatment historically has been a mat­ ering 9 years from 1975 to 1984 at a Veterans ter of controversy, with some advocating Sutton's9 Administration hospital in Virginia. He found 121 approach using and . Others patients with delirium tremens. The numbers considered prescribing alcohol as well as digitalis, 15 decreased yearly from 66 in the first 2 years of sedative: baths,14 cathartics,17 and ergot.16 Mor-

Review article • Griffin et al JAOA • Vol 93 • No 9· September 1993·931 tality was reported from 7.1% to 72.7%. Bostonll lower on average today as compared with those thought that the mortality rate was more closely of 10 years ago. Whether some inadvertent adul­ related to patient age than to type of treatment terant responsible for the delirium tremens has or quantity and duration of intake. been removed is unverifiable. Tavel and coworkers'21 article is referred to The major faciDr, we think, in the decreased inci­ frequently when authors are quoting statistics on dence of delirium tremens is the widespread use mortality from delirium tremens (Table 2). In 1976, of the benzodiazepines in the treatment of alco­ Sellers and Kallant2 reviewed cases of delirium hol withdrawal. The benzodiazepines help in detox­ tremens admitted to Philadelphia General Hos­ ification through the GABA network system in pital from 1950 to 1958. There were 39 deaths in the central nervous system. These medications 250 cases (291 admissions), a mortality rate of also have reduced the mortality rate to near 0%. 15.6%. Fatal cases were most often associated with hyperpyrexia and seizures. The criteria for diag­ Conclusion nosis conforms to the one listed here. The treatment With the advent of prompt treatment with ben­ included fluids, , , and, zodiazepines in therapeutic doses, delirium tremens in two cases, corticotropin; both patients who has been eliminated as a serious of received corticotropin died. Victor,6 in 1953, demon­ alcohol withdrawal. The alcoholic person has devel­ strated that corticotropin was of no use in the oped a cross-tolerance to these medications as well treatment of delirium tremens. This is under­ as the tolerance to alcohop6 To obtain the bene­ standable because corticotropin tends to cause the fit from these drugs, it is therefore important that retention of sodium and water, and current think­ they be given in doses considerably larger than ing seems to suggest that delirium tremens is in those usually used to control anxiety. part caused by overhydration resulting from alco­ hol's chronic effect on antidiuretic hormone. Stud­ ies since that time have not shown a comparable References mortality rate for delirium tremens (Table 2). It is 1. Rothman KJ, Cann CI, Fried MP: Carcinogenicity of dark . now time to stop using Tavel and associates'24 Am J Public Health 1989;79:1516-1520. study as a benchmark for deliriuim tremens mor­ 2. Sellers EM, Kalant A: and withdrawal. N Engl J Med 1976;294:757-762. bidity and mortality. 3. National Center for Health Statistics: Births, marriages, divorces, The mortality rate for those who Cushman22 and deaths for 1991. Monthly Vital Statistics Report, vol 40, no 12. was certain suffered from delirium tremens was 3.3% Hyattsville, Md, Public Health Service, 1992. 4. Diagnostic and S tatistical Manual of Mental Disorders, ed 3, (3 patients). He attributes this low rate to more rev. (DSM-III-R). Washington, DC, American Psychiatric Associa­ effective treatment. He does not state whether tion, 1987, pp 101-103, 131. these deaths were in the patients treated early in 5. Vetter WR, Cohn LH, Reichgott M: Hypokalemia and electro­ cardiographic abnormalities during acute alcohol withdrawal. Arch the study nor what they received as treatment, Intern Med 1967;120:536-541. but the medications he listed were used in relatively 6. Victor M, Adams RD: The effect of alcohol on the nervous system, low doses. Ifthose patients had drunk long enough in Merrit H, Hare CC (eds): Metabolic and Toxic Diseases of the Nervous System. Baltimore, Md, Williams & Wilkins Co, 1953, pp and heavily enough to put them at risk for delir­ 526-573. ium tremens, it is likely they were tolerant to those 7. Victor M: Treatment of alcoholic intoxication and the withdrawal doses of medication; such toleration could account syndrome. Psychosomatic Med 1966;28:636-650. 8. Thompson WL, Johnson RD, Maddrey WL: and par­ for the fact that out of seven reports of delirium aldehyde for treatment of severe delirium tremens: A controlled tremens published during this time only his showed trial. A nn Intern Med 1975;82:175- 180. any fatalities. 9. Sutton T: Delirium Tremens, on Peritonitis, and on Some Other Inflammatory Affections, and on The Gout. London, UK, J ames Some of this decline may be the result of a Moyes, 1813, p 1-77. more strict definition ofthe syndrome. It is possi­ 10. Romano J : Early contributions to the study of delirium tremens. ble that the change in the kinds of alcohol con­ Ann Med Hist 1941;3: 128-139. 11. Boston LN: Delirium tremens (mania e potu ): Statistical study sumed as well as the improvement in the quality of 156 cases. Lancet 1908; 1:18- 19. of the product has made a difference. Klaus D. 12. Lieber CS, Seitz HK, Gano AJ, et al: Alcohol-related diseases Zastrow (vice president, Anheuser-Busch, Inc; and carcinogenesis. Cancer Res 1979 ;39:2963-2886. 13. J elliffe ES, White WA: Diseases ofNervous System. Philadelphia, written communication, June 1992) states that Pa, Lea & Febiger, 1929, p 1066. there have been no significant changes in brewing 14. Ranson SW, Scott GD: The results of medical treatment in methods; however, standards for water and other eleven hundred and six cases of delirium tremens. Am J Med Sci 1911;141:673-687. ingredients are higher than in the past. There are 15. Hoppe HH: Treatment of delirium tremens by spinal puncture, fewer additives. Magnesium levels in beer are stimulation, and use of alkali agents. J Nerv Ment Dis 1918;47:93-99. (Continued on page 935)

932· JAOA· Vol 93 • No 9· September 1993 Review article • Griffin et al 16. Cline WE, Coleman JV: The treatment of delirium tremens. 27. WHO Technical R eport, No. 90, 1955. JAMA 1936;107:404-409. 28. Wacker WE, Vallee BL: Magnesium metabolism (concluded). N 17. Piker P, Cohn JV: The comprehensive management of delirium Engl J Med 1958;259:475-480. tremens. JAMA 1937;108:345-349. 29. Flink EB, Stutzman FL, Anderson AR, et al: Magnesium defi­ 18. Moore M, Gray MG: Delirium tremens: A study of cases at the ciency after prolonged parenteral fluid administration and after Boston City Hospital, 1915-1936. N Engl J Med 1939,220:677-688. chronic alcoholism complicated by delirium tremens. J Lab Clin 19. Isbell H, Fraser lIF, Wilder A, et al: An experimental study of Med 1954;43:169-183. the etiology of 'rum fits' and delirium tremens. Q J Stud Alcohol 30. Meyer JG, Urban K: Electrolyte changes and acid base bal­ 1955;16:1-33. ances after alcohol withdrawal. J Neurol1977;215:135-140. 20. Mendelson J , Wexler D, Kubzansky P, et al: Serum magne­ 31. Martin ME, Mehl J , Wertman M: Clinical studies of magne­ sium in delirium tremens and . J Nerv Ment sium metabolism. Med Clin North Am 1952;1157-1171. Dis 1959;128:352-357. 32. Ragland G: Electrolyte abnormalities in the alcoholic patient. 21. Tavel ME, Davidson W, Batterton TD: A critical analysis of Emerg Med Clin North Am 1990;8:761-773. mortality associated with delirium tremens. Am J Med &i 1961;242:18- 33. Embry CK, Lippmann S: Use of magnesium sulfate in alco­ 29. hol withdrawal. Am Fam Physician 1987;35:167-170. 22. Cheshmedjiev P, Atanassov V: Prophylaxis of the acute psy­ 34. Beard JD, Knott DH: Fluid and electrolyte balance during acute chotic complications in chronic alcoholic cases and the role of the with­ withdrawal in chronic alcoholic patients. JAMA 1968;204:133-137. drawal syndrome in their genesis. Alcoholism 1972;8:107-109. 35. Domschke S, Domschke W, Lieber CS: Hepatic redox state: 23. Wadstein J, Skude G: Does hypokalemia precede delirium Attenuation of the acute effects of induced by chronic con­ tremens? Lancet 1978;2:549-550. sumption. Life Science 1974;15:1327-1334. 24. Cushman P Jr: Delirium tremens: Update on an old disorder. 36. Blazer DG: Alcohol abuse and dependence, in Abrams WE, Postgrad Med 1987;82:117-122. Berkow R (eds): The Merck Manual of Geriatrics. Rahway, NJ, 25. Steinebach R: Ueber die Zerebrospinalflussigkeit und uber die Merck Sharp & Dohme Research Laboratories, 1990, p 1019. wirkung der lumbalpunktion beim delirium potatorum. Dtsch Med Wochnschr 1915;41:369-372. 26. Bleuler E, Berzo J , Luxemburger H: Lehrbuch der Psychiatria, ed 6. Julius Springer, 1924, pp 245-248. Additional bibliography available from the authors on request.

Review article • Griffin et al JAOA· Vol 93 • No 9· September 1993 • 935