1 II and
2 I Departments of Psychiatry, The Medical University of Warsaw, Nowowiejska 27, 00-665 Warsaw, Poland
Received 5 October 2000; in revised form 25 April 2001; accepted 31 May 2001
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ABSTRACT |
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INTRODUCTION |
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Some authors suggest that older persons develop more severe forms of AW than younger patients (Gross et al., 1972; Naranjo and Sellers, 1986
). The hypothesis was proposed that withdrawal symptoms' severity and the likelihood of delirium or seizures increase with advanced age (Liskow et al., 1989
). Most patients suffering from severe forms of AW are between 40 and 50 years old (Gross et al., 1974
), although delirium tremens was also observed in a 9-year-old child (Sherwin and Mead, 1975
). The patients at the greatest risk of fatal withdrawal reactions or death during AW are those aged >45 years (Tavel et al., 1961
; Taylor et al., 1983
; Feuerlein and Reiser, 1986
; Naranjo and Sellers, 1986
; Wasilewski et al., 1989
). However, a severe course of AW may also result from a high level of daily alcohol consumption (Freidman, 1980
; Pristach et al., 1983
; Benzer, 1990
), a long period of intensive drinking, the development of a kindling mechanism (Ballenger and Post, 1978
; Brown et al., 1988
; Lechtenberg and Worner, 1991
; Booth and Blow, 1993
; Wojnar et al., 1999a
), and/or serious co-morbid medical or surgical disorders (Thompson et al., 1975
; Thompson, 1978
; Taylor et al., 1983
; Wojnar et al., 1999b
).
Only a few clinical studies have been performed to assess the impact of age on the course of AW and to evaluate the need for careful intensive treatment of older alcohol-dependent patients (Liskow et al., 1989; Brower et al., 1994
; Foy et al., 1997
; Kraemer et al., 1997
). Some of these studies demonstrated that, compared with young alcohol-dependent persons, elderly patients undergo more severe AW, for which they receive more intensive pharmacological treatment (Liskow et al., 1989
; Brower et al., 1994
). In the studies by Foy and Kay (1995) and Foy et al. (1997), it was reported that patients aged >70 years ran a higher risk of complications in AW, including delirium and hallucinations. The impact of advanced age on the severity of AW delirium was also relevant for the cases of persistent delirium tremens described by Miller (1994) and Hersch et al. (1997).
Other studies, however, questioned age as a risk factor for the development of withdrawal delirium or seizures among in-patients undergoing alcohol detoxifications (Morton et al., 1994; Schaumann et al., 1994
; Mayo-Smith and Bernard, 1995
; Ferguson et al., 1996
; Kasahara et al., 1996
). Kraemer et al. (1997) reported that AW severity, the amount of benzodiazepines used and the duration of pharmacological treatment did not change significantly with age. Moreover, the authors of another study observed that, independently of many other factors, young individuals consuming excessive amounts of alcohol run an even greater risk of developing severe AW (delirium tremens) than the elderly (Kramp and Hemmingsen, 1981
). A unique study of animals to test the effects of ageing on the severity of ethanol-withdrawal symptoms revealed no significant correlation between age and the intensity of withdrawal symptoms in rats (Riihioja et al., 1999
).
This brief overview of clinical research demonstrates that there is still ambiguity concerning the impact of age on the severity and course of AW symptoms. Some studies confirm that age is an important risk factor for severe AW, whereas others contradict this possible association. The disagreement in findings may have resulted from different methodologies used in the respective analyses. The patients studied came from different settings, not only from detoxification units but also from medical wards, and therefore the patients' general somatic condition might have influenced the course of AW. Some studies analysed small-sized samples (Liskow et al., 1989; Brower et al., 1994
). In a few studies, researchers compared patients of only two distant age groups, and such a comparison might have influenced results. Moreover, in assessing withdrawal symptoms, some authors lacked a validated rating scale, and others failed to take into consideration the possible influence of other important factors, e.g. parameters of drinking history or the patients' somatic state.
The aim of our study was to determine the impact of age on the severity of the AW syndrome and on the development of related complications. In order to overcome a number of limitations of the above-mentioned studies, we decided to study the course of AW in a large population of hospitalized patients of several age groups and representing most of the adult withdrawal population.
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PATIENTS AND METHODS |
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Patients with any other concomitant substance dependence were excluded from the analysis to avoid the influence of other factors on the course of AW. The retrospective analysis relied on medical records of 892 patients hospitalized in the years 19731987 and a further 321 patients were observed on a prospective basis in the years 19901999. The final analysis included each patient's most recent available record in order to evaluate the effect of the number of prior detoxifications on the course of the studied AW episode.
The retrospective data (from records) were entered in a structured questionnaire (Szelenberger et al., 1989) by a group of psychiatrists with at least 5 years of experience in treating patients. They received detailed training in using the questionnaire for the purpose of assessing the documentation. Inter-rater reliability of the group was r = 0.838. Data gathered during prospective observation was entered into the same questionnaire.
The questionnaire included five major domains of variables: (1) demographics (sex, age, education, family and professional status); (2) drinking history (age of onset of intensive drinking, duration of harmful drinking, length of the last drinking bout, daily intake of alcohol during the last period, number of prior detoxifications); (3) injuries, somatic disorders in the past and somatic condition during hospitalization [concomitant somatic disorders, heart rate, blood pressure, body temperature, deviations in results of laboratory tests (haemoglobin, red blood cells count, alanine aminotransferase, potassium, urea) and for patients hospitalized from 1990 also mean corpuscular volume, gamma-glutamyltransferase (GGT), glucose and platelet count]; (4) severity of AW symptomatology (according to the scale described below) and the course of AW (duration of symptoms, complications, occurrence of withdrawal seizures, length of hospitalization); (5) pharmacological treatment (pharmacological agents and daily dose; benzodiazepine doses were reported in equivalent milligrams of diazepam).
Depending on their clinical state at the time of admission, patients were classified as being at one or another stage of AW as follows: stage 1, uncomplicated AW (symptoms according to alcohol withdrawal DSM-IV criteria); stage 2, predelirium state (fleeting illusions or hallucinations, slight disorientation, mild difficulties in contact, sleep disorder); stage 3, developing delirium (vivid hallucinations, delusions, psychotic anxiety, but still in contact with reality); stage 4, developed delirium tremens (false psychotic orientation, lost contact with surrounding, disorganized thought, marked agitation, disordered sleep/wake cycle); stage 5, deep consciousness disturbances, without any contact.
The maximum stage of withdrawal syndrome severity was subsequently assessed during hospitalization.
In the group of patients hospitalized from 1990 (n = 321) the maximum severity of AW symptoms during their stay in hospital was evaluated also with the CIWA-A scale (Shaw et al., 1981). The score analysed was that recorded at the onset of the pharmacological treatment administered in hospital. In order to examine the accuracy of the above list of stages of AW severity, we calculated the correlation between the stage of the withdrawal symptoms' severity and the CIWA-A score in this group of patients. The correlation was positive and statistically significant (r = 0.641, P < 0.0001).
In order to assess the possible impact of age on the course of AW, we compared the variables studied across several age groups. For this purpose, we used the interval of 10 years to divide the population of our study into five age groups: <30 years, 3039 years, 4049 years, 5059 years and 60 years. Assessing the course of AW in relation to the age of patients, we considered age as the independent variable, while severity and duration of AW symptoms, complications, occurrence of withdrawal seizures, length of treatment and daily dose of medication were the major dependent variables. Other groups of variables (demographics, drinking and medical history, somatic state) were studied for their possible influence on the AW course and, additionally, for assessment of other differences between age groups of alcohol-dependent patients. We also compared the correlation in all age groups between the severity of AW symptoms, the duration of AW symptoms, and the occurrence of withdrawal seizures on the one hand with the duration of harmful drinking, the number of prior detoxifications, the length of the preceding drinking bout, and daily alcohol intake during the last bout on the other.
In a statistical analysis of the results, the 2-test for categorical data, analysis of variance (ANOVA) for continuous variables, KruskalWallis ANOVA and non-parametric correlation analysis (Kendall's Tau) were performed where appropriate, with the significance level for probability of the null hypothesis set to 0.05. SPSS statistical software was used (Norusis, 1993
).
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RESULTS |
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Demographic characteristics are presented in Table 1. The age groups did not differ in respect of gender. There were significant differences in other demographic variables: marital status, education, employment, and number in households. As expected, we observed significant trends for more widowed, pensioned, and living-alone persons as age increased.
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The associations of the severity of AW, its duration, and the occurrence of withdrawal seizures with some parameters of drinking history differed significantly between the age groups, as shown in Table 4. Even though no significant differences were found between age groups in the duration or severity of the AW symptoms, the correlation between the duration of AW and the level of alcohol intake during the last drinking bout was meaningful in patients aged >50 years. On the other hand, the duration of AW symptoms correlated highly with the length of the last drinking bout only in young patients (those aged <30 years).
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Occurrence of withdrawal seizures was positively associated with the length of the preceding bout in patients >50 years, and with the number of prior episodes in patients >40 but <60 years old.
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DISCUSSION |
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The studies of Liskow et al. (1989) and Brower et al. (1994) compared patients from distant age groups: 5860 and
3335 years. It has been suggested that the results of studies designed in such a way might reflect differences in the course of AW specific to the younger groups rather than to the elderly (Kraemer et al., 1997
). Most patients hospitalized for detoxification are 3050 years of age (68.5% of the patients in our study). We selected patients of several age groups, divided by the interval of 10 years, in order to include a representative group of the adult withdrawal population.
There are other studies which, like ours, failed to find greater severity of AW symptoms in the elderly. For example, Kraemer et al. (1997) found that AW severity, as measured by CIWA-Ar scores and benzodiazepine requirement, did not vary significantly with age. As in our study, older patients required longer hospital stays. The study supported recommendations of the American Medical Association (1996) that older patients with AW require close supportive care in well-monitored settings. Kraemer et al. (1997) reported also that older patients (60 years) were at higher risk for transient cognitive impairment (i.e. delirium) during AW. We also found a higher frequency of delirium tremens in patients
60 years (34%), but, compared with other age groups, the difference was not statistically significant. The observed rate of delirium in the study of Kraemer et al. was 14%, but most of those cases were states of delirium due to a general medical condition. Only 1% of the total study sample was considered AW delirium, which is a very low value, compared with our result. These authors suggested that most cases of delirium during AW in studied older populations were not classic delirium tremens (for Kraemer et al., delirium tremens signifies only the most severe cases of delirium occurring with confusion, agitation and extreme autonomic hyperactivity). In our study, we assumed delirium tremens to be synonymous with alcohol withdrawal delirium (according to DSM-IV criteria) and we did not distinguish a state of general delirium when the patient was simultaneously undergoing AW. Moreover, it is surprising that withdrawal severity scores (CIWA-Ar) in the study of Kraemer et al. (1997) were comparable across different age groups, while the delirium rate was higher in older patients. The CIWA-Ar score also reflects cognitive disturbances during AW and, in our opinion, withdrawal severity scores should increase with growing delirium incidence. It is, however, probable that younger patients of Kraemer et al.'s population experienced, for example, particularly elevated autonomic hyperactivity, and that is why the CIWA-A score was comparable in the studied groups. In the Polish sample of alcohol-dependent patients, we observed also similar withdrawal severity across all age groups.
In our study, we found a higher frequency of hypertension, hypokalaemia, coexisting somatic diseases and somatic complications of AW, as age increased, which is consistent with the general observation that older patients are at a higher risk of somatic morbidity, especially if they drink alcohol intensively (Hurt et al., 1988; Schuckit et al., 1995
). However, a comparable delirium rate in all groups is slightly confusing, because of the difference in somatic state between age groups. It is well known that concomitant somatic disorders make the course of AW more severe (Thompson et al., 1975
; Ferguson et al., 1996
; Wojnar et al., 1999b
). In our study, older patients were hospitalized for a longer period of time, despite having similar profiles of withdrawal severity and requiring similar amounts of benzodiazepines. Their longer hospitalizations could obviously be due to the above-mentioned differences in the somatic condition between older and younger patients. Furthermore, the medical staff might have been more caring towards the older patients, which might have led to their longer hospitalization. This result is consistent with the findings in Kraemer et al. (1997).
Kraemer et al. (1997) suggested that cognitive complications of AW in older patients may be attributable to the adverse effects of medication used, rather than to being a direct effect of AW. Benzodiazepines are known to be more slowly metabolized, to achieve higher blood concentrations and increased clinical effects in the elderly (Ozdemir et al., 1996; Peppers, 1996
). Some studies reported that older patients were treated with higher doses of benzodiazepines for AW than younger adults (Liskow et al., 1989
), which, according to the hypothesis put forth by Kraemer et al. (1997), might consequently lead to more frequent occurrence of delirium tremens in older patients. Our study, like the studies of Kraemer et al. (1997) and Brower et al. (1994), showed that hospitalized patients of all age groups needed comparable amounts of benzodiazepines during the treatment of withdrawal symptoms. This finding was consistent with the similarities in the severity of AW course in all the groups we studied. However, it is probable that, despite similar doses of medication, older patients achieved higher blood concentrations of benzodiazepines, which could potentially alleviate the risk of more severe AW symptoms. Therefore, older alcoholics might actually undergo more intense AW episodes, but these would be hidden by pharmacological treatment.
An analysis of the relationships of AW severity, duration of symptoms, and occurrence of seizures with variables of drinking history yielded some ambiguous results. The only clear association was that of longer duration of AW with a high level of alcohol consumption in patients aged >50 years, which confirms previous findings (Freidman, 1980; Pristach et al., 1983
; Benzer, 1990
). Severity of symptoms correlated with daily alcohol intake and duration of harmful drinking in those aged 3049 years. These diverse relationships between AW course and patients' age could explain, to some extent, the variation of results in other studies. Some studies have found that drinking history is a predictor of withdrawal severity (e.g. Ballenger and Post, 1978
; Lechtenberg and Worner, 1992
), while others have not (e.g. Brown et al., 1988
; Wojnar et al., 1999a
). It is possible that studied populations of patients suffering from AW differed in respect of age and, presumably, in other factors. Our findings suggest that certain variables of drinking history can be predictors of withdrawal severity only in patients >50 years old. Younger age can therefore be considered a mitigating factor.
Some authors suggested that the occurrence of more severe forms of AW in the elderly may result from a kindling phenomenon (Ballenger and Post, 1978; Brown et al., 1988
; Lechtenberg and Worner, 1991
; Booth and Blow, 1993
). Both in our previous study (Wojnar et al., 1999a
), and in the present study (performed on the more extended population), we observed that the relationship between the severity of AW symptoms (i.e. occurrence of delirium tremens) and the number of previous AW episodes (as a manifestation of the kindling mechanism) was most significant in patients >60 years. On the other hand, a correlation between the occurrence of withdrawal seizures and the number of prior detoxifications was significant for younger groups of patients (>40 but <60 years). Our findings did not result from a different number of previous AW episodes in age groups. The number of prior admissions for detoxification did not differ between age groups, although older alcoholics had been problem drinkers for significantly longer periods than younger persons. More apparent manifestations of kindling in older alcoholics may be due to the more pronounced CNS sensitivity of this group of patients; they may be more susceptible to the neurophysiological, psychopathological and somatic consequences of prolonged alcohol drinking and repeated episodes of withdrawal. Consistent with our other findings, the correlation between the duration of treated AW syndrome and the recent daily amount of alcohol consumed was only prominent in elderly patients, despite the fact that they drank smaller quantities than the younger patients.
The main limitation of our study is the fact that our analysis relied to a large extent on medical records. Retrospective search of records might not yield reliable data, despite the use of standardized procedures (structured questionnaire, trained study team). We therefore supplemented our retrospective findings using a prospectively studied sample (patients hospitalized since 1990). Moreover, we attempted to standardize measures of AW severity assessment and to confirm retrospective findings using a validated CIWA-A scale during admissions from 1990 onwards.
Although we gathered data for a large population of in-patients in AW, this included a relatively small number aged 60 years. Unfortunately, in the prospective part of the study, we only had eight patients of that age, a small number which could have influenced the statistical significance and thus the validity of our results. The differences in numbers of patients between age groups reflect typical age distribution of alcohol-dependent patients hospitalized at the Nowowiejski Hospital: elderly patients are relatively infrequent. Moreover, our studied population consisted of in-patients admitted for detoxification to a city general psychiatric hospital; many of these patients suffered from delirium tremens. This fact probably accounts for the difference in delirium rate between our findings and that of other studies. Most other studies were conducted in detoxification units and focused on uncomplicated AW, with only sporadic incidence of delirium of the order of a few per cent (Brown et al., 1988
; Lechtenberg and Worner, 1991
; Booth and Blow, 1993
; Kraemer et al., 1997
).
In conclusion, our study does not support several earlier reports that AW may be more severe in older alcoholics. However, it is worth remembering that the population of alcohol-dependent persons aged >40 years is more susceptible to serious somatic disorders and the somatic complications of AW. Moreover, those older patients who experience repeated withdrawal episodes are more prone to develop withdrawal seizures or delirium tremens. Therefore, they need careful medical assessment, monitoring and treatment in closely supervised detoxification settings.
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FOOTNOTES |
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