a) What are the benefits and risks of unplanned ‘emergency’ detoxification (medically assisted withdrawal) in acute medical settings vs discharge?
b) What criteria should be used to admit a patient with AAW for ‘unplanned emergency’ detoxification?

ReferenceStudy type
Evidence level
Number of patientsPatient characteristicsIntervention
Treatment regimen
ComparisonLength of follow-upOutcome measures Associations
Statistical analysis
Source of funding
Duka T, Townshend JM, Collier K et al. Impairment in cognitive functions after multiple detoxifications in alcoholic inpatients. Alcoholism: Clinical & Experimental Research. 2003; 27(10):1563–1572. Ref ID: 87Prospective cohort 2++N=85Patients undergoing detoxification in an inpatient setting. All patients had ceased pharmacological therapy for the treatment of withdrawal for at least two weeksTwo or more medically supervised detoxifications
N=6

Total number of previous detoxifications (including unsupervised and medically supervised): ANCOVA not performed (results not reported)

Treatment regimen: chlormethiazole (mean dose 192 mg, probably fixed dose)
One or fewer medically assisted detoxifications (LO)
N=36

Mild to moderate social alcohol drinkers recruited from a University

N=43
NAStroop colour naming task, maze learning vigilance taskMedical research council
Effect
There were no significant differences (ANCOVA) were reported between patients with a high number of previous detoxifications and those with a low number on the stroop task, maze learning or vigilance tasks (ns)
Malcolm R, Roberts JS, Wang W et al. Multiple previous detoxifications are associated with less responsive treatment and heavier drinking during an index outpatient detoxification. Alcohol. 2000; 22(3):159–164. Ref ID: 97Prospective cohort 2++N=136Patients with alcohol dependence and withdrawal (DSM-IV)

Inclusion: ≥ 26 Mini mental state examination CIWA-Ar ≥ 10

Exclusion: substance abuse, history of head injury but patients with a history of alcohol related seizures were included

Setting: Patients recruited via a trial comparing lorazepam and carbamazepine in the outpatients treatment of alcohol withdrawal

Patient population: mean age 73%, 87% white, mean no. of standard drinks in 14 days prior to detoxification 177, mean alcohol dependence scale score 22, mean number of years drinking 21 yrs, 73% male

No significant differences were reported at baseline
Lorazepam and carbamazepine fixed dose regimen

Previous detoxifications ≤ 1

N=103

Lorazepam N=58

Carbamazepine
N=45
Previous detoxifications > 1 (range 2 to 5)

N=33

Lorazepam
N=17

Carbamazepine
N=16
NAStatistical analysis: ANCOVA and logistic regressionNone reported
Effect
Low vs high detoxifications
Patients who had undergone multiple detoxifications compared with those with 0 to 1 previous detoxification had:
A significantly slower rate of decline on the CIWA-Ar from day one to four of the detoxification (no data reported p<0.05)

There was no significant difference between patients with o to 1 previous detoxifications compared with those with multiple detoxifications on:
CIWA-Ar score at baseline (no data reported ns)
Schuckit MA, Tipp JE, Reich T et al. The histories of withdrawal convulsions and delirium tremens in 1648 alcohol dependent subjects. Addiction. 1995; 90(10):1335–1347. Ref ID: 1013Prospective cohort 2++N=1648Patients who were alcohol dependent (DSM-III-R)

Setting: Not specified

Patient population: Mean age 38 yrs, 33% female, 77% Caucasian, mean age of alcohol dependence 24 yrs
History of severe withdrawal

Presence of DTs and/or seizures)

N=211
Control (no history of severe withdrawal)

N=1437
NAOutcomes taken from Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA)

Association between a history of DT and convulsion and:
Drinking history Withdrawal epidodes (***) Withdrawal symptoms

Univariate tests and regression
National Institute for Alcohol Abuse and Alcoholism
Effect
Incidence
188/1648 (11%) patients experienced delirium tremens, including 31 (2% of the total sample and 17% of those with DTs) who ever had a grand mal convulsion during withdrawal.
Another 23 people (1%) of the total had a history of convulsions but not history of DTs. In total 211/1648 (13%) (range 1 to 45) reported DTs and/or a history of convulsions.
Multivariate hierarchical logistic regression model
A history of DTs and/or convulsions compared with no history of DTs and/or convulsions was significantly associated with:
A higher number of drinks in 24 hrs (lifetime) (41 vs 25) (OR 1.02, 95%CI 1.01 to 1.03; p<0.001)
A history of more withdrawal episodes (28 vs 16) (OR 1.01, 95%CI 1.00 to 1.02; p<0.01)

Univariate analyses
Patients with a history of DTs and/or convulsions compared to those without was associated with a significantly:
Longer period of heavy drinking (excluding abstinence periods) (13 vs 10 yrs; p<0.001)
Days of drinking per week (drinkers, last six months) (41 vs 25; p<0.001)
Number of withdrawal symptoms (worst episode) (6 vs 4; p<0.001)

None of the factors were significant predictors of DTs and/or convulsions in the multivariate analysis
Wetterling T, Driessen M, Kanitz RD et al. The severity of alcohol withdrawal is not age dependent. Alcohol & Alcoholism. 2001; 36(1):75–78. Ref ID: 122Prospective cohort 2++N=723Patients with alcohol withdrawal

Setting: Alcohol detoxification unit in a general hospital (patients with acute medical or surgical disorders)

Patient population: M:F 518:205, mean age 43 yrs
Age groups compared:
≤ 29 yrs, 30 to 59 yrs and ≥ 60 yrs

Treatment regimen: symptom-triggered carbamazepine
See interventionNAAssociation between age and severity of alcohol withdrawal

Severity of alcohol withdrawal and drinking history, number of prior detoxifications (no definition provided)

Statistical analysis: univariate and regression
None reported
Effect
The incidence of DT was 8.4% for the total population

Logistic regression analysis
Withdrawal severity (maximum AWS score) was not predicted by:
Age (ns)
Duration of alcohol dependence (ns)
Alcohol intake/day (ns)
Prior detoxification (ns)
Booth BM, Blow FC. The kindling hypothesis: further evidence from a U.S. national study of alcoholic men. Alcohol & Alcoholism. 1993; 28(5):593–598. Ref ID: 200‘Retrospective cohort 2+N=6818Patients admitted for a short detoxification episode (0 to 5 days) with alcohol dependence (ICD-9)

Setting: medical centre

Exclusion criteria: females, admission for rehabilitation
Withdrawal problems

N=461

Unspecified seizures

N=193

Treatment regimen: not specified
No withdrawal problems

N=6357

No unspecified seizures

N=6625
NANo. of hospitalisations (determined by hospital notes) and seizure frequency and withdrawal problems (DT, alcoholic hallucinations, alcoholic dementia) Statistical analysis: univariate and multivariate analysisNational institute for alcoholism and alcohol abuse
Effect
During the index period
461/6818 (7%) experienced withdrawal problems (DT, alcoholic hallucinations, alcoholic dementia)
193/6818 (3%) had unspecified seizures

Three years before index detoxification
Withdrawal problem (DT, alcoholic hallucinations, alcoholic dementia) vs no withdrawal problem
Univariate analysis (confirmed by multivariate analysis)
There was a significant difference between the number of people who had withdrawal problems and those who did not with respect to:
Previous alcohol-specific hospitalisation days (10.01 vs 7.13; p<0.05)

There was no significant difference between people who had withdrawal problems and those who did not with respect to:
The number of previous alcohol-specific hospitalisations (0.95 vs 0.82;ns)

There was a significant difference between those patients with unspecified seizures and those without with respect to:
Previous alcohol-specific hospitalisations (1.48 vs 0.81; p<0.01)
Previous alcohol-specific hospital days (14.52 vs 7.12; p<0.01)
Lukan JK, Reed DN, Jr., Looney SW et al. Risk factors for delirium tremens in trauma patients. Journal of Trauma-Injury Infection & Critical Care. 2002; 53(5):901–906. Ref ID: 1139Retrospective cohort 2+N=1856Patients admitted for trauma who developed DT whilst in hospital or presenting with a positive blood alcohol concentration (BAC) on admission.

Setting: General hospital

Patient population: DT group – 90% male, 92% white, 63% > 40 yrs*, BAC mean 43 mmol/L*, BAC ≥ 200 mg dL 60%*, 32% car accident*, 17% fall*, assault 10%, stab wound 12%, Glasgow Coma Score ≤ 7 9%

Non-DT – 85% male, 77% white, age > 40 yrs 32%*, BAC mean 41.2 mmol/L, BAC ≥ 200 mg dL 48%*, 50% car accident*, 8% fall, assault 10%, stab wound 8%, Glasgow Coma Score ≤ 7 15%

Denotes significant difference
Patients with DT

N=104 (one patient excluded)

Treatment regimen: Various but mainly administration of benzodiazepines
Non-DT group
N=1751
NAAssociation between Statistical analysis: univariate and logistic regressionNone reported
Effect
Univariate analysis
The following were significant predictors of whether a patient developed DT or not:
The following were age > 40 yrs (OR 3.21, 95%CI 2.14 to 4.81; p<0.001)
blood alcohol concentration ≥ 43 mmol/L (200 mg/dL) (OR 1.69, 95%CI 1.08 to 2.62; p<0.05)

The following were not significant predictors of whether a patient developed DT or not:
mean blood alcohol concentration on admission (ns)

Regression analysis
Age > 40 yrs but not blood alcohol concentration ≥ 43 mmol/L (200 mg/dL) remained a significant predictor of DT in the multiple regression model (OR adjusted age > 40 yrs 2.98; 95%CI 1.97 to 4.51; p<0.001)
F Ferguson JA, Suelzer CJ, Eckert GJ et al. Risk factors for delirium tremens development. Journal of General Internal Medicine. 1996; 11(7):410–414. Ref ID: 1101Retrospective cohort 2+N=200Patients with alcohol withdrawal or detoxification

Setting: Internal medicine hospital at general hospital

Exclusion: Presence of DT on admission

Patient population: mean age 42 yrs, 85% male
Delirium tremens
N=48

Treatment regimen: Scheduled and as needed benzodiazepines
No delirium tremens N=152NAAssociation between delirium tremens and the number of days since the last drink and the number of previous withdrawal episodes (obtained from medical records but not further defined)

Statistical analysis: Univariate and logistic regression
Bureau of health professions, health resources and services administration
Effect
Incidence of DT
48/200 (24%) developed delirium tremens, of these 4/48 (8%) died
Univariate analysis
The development of delirium tremens was significantly associated with:
More days since the last drink (p<0.10)

There was no significant association between the development of delirium tremens and:

History of previous withdrawal events (ns)

In the multiple regression analysis more days since the last drink was an independent predictors of the development of delirum tremens (OR 1.3; 95%CI 1.09 to 1.61)
Vinson DC, Menezes M. Admission alcohol level: a predictor of the course of alcohol withdrawal. Journal of Family Practice. 1991; 33(2):161–167. Ref ID: 1011Retrospective cohort 2+N=233

N=119 non-medical unit

N=113 medical unit
Patients admitted for alcohol withdrawal

Setting: 1) nonmedical social detoxification setting. Patients with severe withdrawal and transferred elsewhere. 2) medical detoxification unit

Patient population: Non-medical: mean age 37 yrs, male:female 99:2, mean daily alcohol consumption 377 g/d

Medical: mean age 45 yrs, all male, mean daily alcohol consumption 361 g/d
Non-medical social detoxification setting.

N=119

Patients with severe withdrawal and transferred elsewhere.

Treatment regimen: chloridazepoxide prn
Medical detoxification unit

N=114

Treatment regimen as for intervention
NAAlcohol level on admission and: Amount of chlodiazepoxide used during withdrawalNone reported
Effect
Non-medical setting
Linear regression analysis showed a significant relationship between breath alcohol levels on admission and severity of withdrawal (amount of chlordiazepoxide used in first 48 hrs) (R2=0.26;p<0.0001). This reduced to p=0.002 when AST was entered in to the equation. When patients were classified in to two groups based on the median level of alcohol on admission ( 33 mmol/L (150 mg/dL vs > 33 mmol/L) higher levels were associated with more severe adverse outcomes, including transfer to acute care hospital for medical detoxification and a maximum withdrawal assessment score of greater than 6 (indicating medical consultation is required). When the same threshold was applied to the medical setting, the threshold distinguished between those patients who required a total of 50 mg chlodiazepoxide or less and those who required more.
Medical setting
Linear regression analysis showed a significant relationship between breath alcohol levels on admission and severity of withdrawal (R2=0.41;p<0.0001). This level of significance remained the unaltered when AST was entered in to the equation.
Kraemer KL, Mayo SM, Calkins DR. Impact of age on the severity, course, and complications of alcohol withdrawal. Archives of Internal Medicine. 1997; 157(19):2234–2241. Ref ID: 50Retrospective case series 3N=284

Stratified random sampling to ensure equal samples across age groups
Patients with alcohol withdrawal

Setting: alcohol detoxification unit

Exclusion: comorbid drug abuse

Patient population: Almost 100% male population
Comparison across the following age groups:

<40 (N=56), 40 to 49 (N=70), 50 to 59 (N=74), 60 to 69 (N=63), ≥ 70 (N=21)

Treatment regimen: Symptomtriggered chlordiazepoxide
See interventionNAStatistical analysis: univariate and regression (adjusted for limited variables). P values adjusted for multiple outcomesNone reported
Effect
Incidence
The incidence of current DT was 1% (N=3)
The incidence of past DT ranged from 3/21 (14.3%) (≥ 70 yrs) to 28/74 38% (50 to 59 yrs)
The incidence of past withdrawal seizures ranged from 1/21 (5%) (≥ 70 yrs) to 17/74 (23%) (50 to 59 yrs)
The association between past DT, past withdrawal seizures and age were reported in the univariate analysis only
There was no significant difference between the age groups (<40 vs 40 to 49 vs 50 to 59 vs 60 to 69 vs ≥ 70) with respect to:
Mean severity of alcohol withdrawal (maximal CIWA-Ar score) (ns)
Mean initial CIWA-Ar score (ns)
Kraemer KL, Mayo SM, Calkins DR. Independent clinical correlates of severe alcohol withdrawal. Substance Abuse. 2003; 24(4):197–209. Ref ID: 86Retrospective case review 3N=284Patients admitted to an acute inpatients detoxification unit

Mean age 51 yrs, 99%male, 20% employed, 19% homeless, mean duration of drinking 25 yrs

Setting: Inpatient detoxification unit
Treatment regimen: Fixed and symptom triggeredSeverity of alcohol withdrawal (600 mg or more, total, cumulative benzodiazepine (expressed in chloridazepoxide equivalents))NAUse of an early morning eye opener, initial CIWA-Ar score, admission serum AST ≥ 80 U/L, past benzodiazepine use, history of delirium tremens, participation in two or more prior alcohol treatment programs, daily alcohol intake, no. of drinking days over past month, no. of past withdrawal episodes

Statistical analysis: multivariate logistic regression
None reported
Effect
The incidence of severe withdrawal was 25%

Multivariate logistic regression
Predictors of severe withdrawal (600 mg or more, total, cumulative benzodiazepine (expressed in chloridazepoxide equivalents)):
history of delirium tremens (OR 2.9; p=0.007)
participation in two or more prior alcohol treatment programs (OR 2.6; p=0.01)

There was no significant association (all were significant in the univariate but not the multivariate analysis) between severity of withdrawal (600 mg or more, total, cumulative benzodiazepine (expressed in chloridazepoxide equivalents) and:
daily alcohol intake (ns)
no. of drinking days over past month (ns)
no. of past withdrawal episodes (ns)
history of withdrawal seizure (ns)
Lechtenberg R, Worner TM. Total ethanol consumption as a seizure risk factor in alcoholics. Acta Neurologica Scandinavica. 1992; 85(2):90–94. Ref ID: 207Prospective case series 3N=500Patients with alcoholism who were at potential risk of:

Dangerous or disabling withdrawal, high risks of seizures, DT or hallucinations, failure of previous outpatient detoxification, unstable social situation (admission criteria)

Setting: Alcohol detoxification unit

Patient population: mean age 41 yrs, mean no. of admission 2, mean alcohol use duration 25 yrs, mean alcohol consumption 293 g/day, male:female 81:17
Association between ethanol consumption and seizure risk Treatment regimen: not statedNANADetoxifications (from patient reported and hospital records, no further definition provided), seizure history, alcohol use history

Statistical analysis: Univariate and discriminant function analysis
None reported
Effect
There were no seizures during the current episode of withdrawal
55/98 patients reported a history of alcohol withdrawal seizures
Mean number of previous detoxification admissions 2

Discriminant function analysis
The following were not correlated with prevalence of seizure history:
Years of alcoholism (R2-Ad 0.007, F=2.6; ns)
Age (ns, no further details reported)

Detoxification admission was correlated with prevalence of seizure history (R2-Ad 0.041, F=15.1; p<0.0001)
Lechtenberg R, Worner TM. Relative kindling effect of detoxification and non-detoxification admissions in alcoholics. Alcohol & Alcoholism. 1991; 26(2):221–225. Ref ID: 1126Retrsospecitve case series 3N=400Patients requesting admission for alcohol detoxification
Inclusion criteria: Alcoholism service accepts patients with potentially dangerous or disabling symptoms. Patients were eligible if they had failed outpatient detoxification or were in unstable social situations

Setting: Alcoholism service

Patient population: male:female 340:60 mean age 41 yrs, mean number of previous detoxification 2, mean number of years of alcohol consumption 25
History of seizure

N=84
Treatment regimen not specified
No history of seizure

N=316
NaSeizure prevalence (associated with alcohol withdrawal but not in all cases) and detoxification admission (not defined),

Statistical analysis: univariate and disciminant function analysis
None reported
Effect
Incidence of seizures
84/400 (21%) of patients had a history of a seizure. No seizures were reported in the current hospital admission for detoxification.

There was a significant association between a history of a seizures and the total number of previous detoxification admissions (mean 2, R2-Ad 0.035, F=13.2; p<0.001).

The following were not significantly associated with a history of seizures and:
Age (ns)
Years of alcoholism (ns)
Palmstierna T. A model for predicting alcohol withdrawal delirium. Psychiatric Services. 2001; 52(6):820–823. Ref ID: 1099Prospective case series 3N=334Patients seeking treatment for alcohol withdrawal

Setting: Psychiatric and dependency emergency unit

Patient population: male:female 251:83 Recent consumption of more than 250 g pure alcohol/daily for at least three weeks 132/334 (40%)
Risk of developing alcohol withdrawal delirium (DSM-IV)

Treatment regimen: fixed dose oxazepam and diazepam prn
NARisk of DT and: Previous DT, previous epileptic seizure, epileptic seizure within past 48 hrs, recent consumption of > 250 grams pure alcohol daily for at least three weeks, alcohol concentration of more than 1 g/litre of body fluid regardless of withdrawal symptoms, more than 24 hrs since the last drink, duration of current episode of current drinking

Statistics: univariate and multivariate
None reported
Effect
Incidence of delirium
145/334 (43%) had previously experienced alcohol withdrawal delirium
139/334 (42%) had a previous epileptic seizure
23/334 (7%) had a epileptic seizure in the past 48 hrs
Univariate analysis
Risk of developing DT is significantly associated with:
Previous epileptic seizure (p<0.001)
Previous alcohol withdrawal delirium (p<0.001)

The risk of developing DT was not significantly associated with:
Epileptic seizure within the past 48 hrs (ns)
recent consumption of > 250 grams pure alcohol daily for at least three weeks (ns)
alcohol concentration of more than 1 g/litre of body fluid regardless of withdrawal symptoms (ns)
more than 24 hrs since the last drink (ns)
duration of current episode of current drinking (ns)

Multiple regression
Risk of developing DT was significantly associated with
Previous epileptic seizure (p<0.05)
Previous delirious episode (p<0.05)

A previous history of alcohol withdrawal delirium and of epileptic seizures independently contributed only 6% and 6.8%, respectively, to the risk of developing delirium
Daryanani HE, Santolaria FJ, Reimers EG et al. Alcoholic withdrawal syndrome and seizures. Alcohol & Alcoholism. 1994; 29(3):323–328. Ref ID: 469Prospective cohort 2−N=72

N=68 could describe previous withdrawal episodes
Patients with alcohol withdrawal syndrome (tremour, hallucinations, DT or seizure)

Inclusion criteria: under 65 yrs and daily ethanol intake of at least 80 g/day

Setting: Internal medical unit

Patient population: 93% male, mean age 45 yrs, mean duration of chronic alcohol use 20 yrs
Treatment regimen: diazepam prnNAAssociation between seizure on admission and: Prior history of seizure
Mean alcohol intake/day
Mean duration of alcohol use

Statistics: univariate analysis for outcomes reported here
None reported
Effect
Incidence of a history of DT and seizure
26/68 (38%) described a past history of seizures
39/68 (57%) had a past history of DT
Incidence of DT and seizure on admission
33/72 patients had a seizure on admission
18/33 developed DT

There was a significant association between a seizure on admission and a prior history of a seizure (p=0.0001)
There was no significant association between the presence of seizures and:
Mean alcohol intake/day (ns)
Mean duration of alcohol misuse (ns)
Fiellin DA, O'Connor PG, Holmboe ES et al. Risk for delirium tremens in patients with alcohol withdrawal syndrome. Substance Abuse. 2002; 23(2):83–94. Ref ID: 486Case control 2−N=60Patients undergoing detoxification

Setting: Inpatient detoxification unit

Exclusion criteria: Signs and symptoms that may indicate early manifestations of DT, no alcohol use in the prior 72 hrs (and were therefore at risk of alcohol withdrawal), discharge within 24 hrs

Patient population: 100% male, 80% white, mean age 49 yrs

There were no significant differences at baseline
Patients with delirium tremens (DSM-IV)

N=15
Patients without DT

N=45
NAHistory of DT and prior seizure, or DT

Univariate statistics
None reported
Effect
Cases with a history of delirium tremens were significantly more likely than controls with out a history to have experienced:
a prior alcohol withdrawal seizure (33 vs 20%, OR 1.9, 95%CI 0.43 to 8.3)
a prior DT (47 vs 24%, OR 2.6, 95%CI 0.64 to 10.5)
a prior complicated alcohol withdrawal syndrome (alcohol withdrawal seizure or DT) (53 vs 27%, OR 3.1, 95%CI 0.94 to 1.05)

There was no significant difference between case with a history of delirium tremens and those control without a history on:
Number of previous alcohol detoxifications at a medical centre (ns)
Mayo SM, Bernard D. Late-onset seizures in alcohol withdrawal. Alcoholism: Clinical & Experimental Research. 1995; 19(3):656–659. Ref ID: 181Prospepective cohort 2−N=1044 (cohort)

From the cohort N=10 patients with seizure matched with N=30 control patients without a seizure
Patients admitted for alcohol detoxification

Setting: Alcohol detoxification unit, Medical Centre

Patient population:
N=10 patients with seizure

Treatment Regimen: Fixeddose and prn oxazepam
N=30 control patients without a seizureNAAssociation between seizure status and: age, history of withdrawal seizures, prior detoxifications (no definition provided), history of DT

Statistical analysis: univariate
None reported
Effect
The incidence of seizures (witnessed) was 11/1044 (1.1%). The seizures occurred 52 to 306 hrs after admission.
A significantly greater proportion of those patients who had a seizure in the current admission had a history of withdrawal seizures compared with patients with a history (50 vs 13%; p<0.05)

There was no significant difference between the proportion of patients who had a seizures and those who did not with respect to:
Age (ns)
Previous detoxifications (ns)
History of DT (ns)
Shaw GK, Waller S, Latham CJ et al. The detoxification experience of alcoholic inpatients and predictors of outcome. Alcohol & Alcoholism. 1998; 33(3):291–303. Ref ID: 1014Prospective cohort 2−N=160Patients with alcohol dependence requiring medically assisted withdrawal

Mean age 44 yrs, 59% socially unstable, 33% regular employment, male:female 131:29

Setting Detoxification unit in psychiatric hospital
Treatment regimen: Fixed schedule chlomethiazoleSeverity of alcohol withdrawal (8 items score 3 to 89)
High grade 36 to 89
Medium 5 to 35
Low 3 to 15
NANo. of previous detoxifications Severity of dependence (see text) Previous experience of withdrawal symptoms, family history of alcoholism

Statistical analysis: stepwise multiple regression
None reported
Effect
Predictors of severity of withdrawal
The proportion of patients experiencing high, medium and low grade withdrawal was 41/160, 77/160 and 42/160 respectively
Incidence of seizures 5/160 (3%) but two patients were epileptic

There was a significant difference between high vs. the medium and low scores of the severity of withdrawal scale for:
Alcohol dependence (SADQ) (high vs . medium and low) (41 vs 33 and 31; p<0.05)
Daily intake (U) on heavy drinking day (42 vs 33 and 31; p<0.05)
No. of detoxifications (7 vs. 2 and 1; p<0.05)
No. of years of heavy drinking (5 vs. 11 and 11; p<0.05)

In a stepwise multiple regression model, the following were predictors of severity of alcohol withdrawal:
Number of previous detoxifications (partial regression coefficient B=0.943)
Severity of alcohol dependence (SADQ) (B=0.327)
Previous experience of alcohol withdrawal symptoms (B=6.100)
Family history of withdrawal (B=2.069)
Multiple r2 = 0.342
Worner TM. Relative kindling effect of readmissions in alcoholics. Alcohol & Alcoholism. 1996; 31(4):375–380. Ref ID: 168Retrospective cohort 2−

Unable to identify where discriminant function analysis or regression analysis has been performed
N=360Patients admitted to alcohol detoxification

Setting: Detoxification unit in a hospital

Patient population: Seizure-positive male 55/68, mean age 40 yrs, mean duration of alcohol use 24 yrs, mean amount of alcohol 315 g/day

Seizure-negative: male 236/292, mean age 40 yrs, mean duration of alcohol use 24 yrs, mean amount of alcohol 316 g/day

There were no significant differences at baseline
Seizure-positive
N=68

Treatment regimen: Chlordiazepoxide based on signs and symptoms or fixed dose (patient with seizure history)

Seizure history based on self or carer report and medical records
Seizure-negative
N=292
Admissions over 5 yr periodNumber of previous detoxifications Breath ethanol on admission

Statistical analysis: t-tests and regression analysis
None reported
Effect
Seizure-positive vs seizure-negative:
At the initial admission a history of seizures (positive N=16 vs negative N=44) was associated with the number of previous detoxifications:
Mean number of detoxifications (2.78 vs 1.45; p<0.01)
On re-admission patients a history of seizures (positive N=26 and negative N=49) was associated with the number of previous detoxifications:
Mean number of detoxifications (4.50 vs 2.83; p=0.0001)

There was no association between a history of seizures and breath ethanol on admission or re-admission(ns)
Wright T, Myrick H, Henderson S et al. Risk factors for delirium tremens: a retrospective chart review. American Journal on Addictions. 2006; 15(3):213–219. Ref ID: 1027Retrospecitve case-control 2−N=56Patients (cases) with alcohol withdrawal delirium (ICD-9) and controls with alcohol withdrawal (ICD-9)

Exclusion: females

Setting: Medical centre (including medicine department, ICU, psychiatry and surgery)

Patient population: mean age 54 yrs, 66% Caucasian, 23% employed

No significant differences were reported at baseline
Delirium tremens
N=28

Treatment regimen: benzodiazepines but schedule not specified
No delirium tremens

N=28
NARisk of DT and: History of DT (documented in medical notes), no. of previous detoxifications (from medical records but not further definition given), drinking history

Statistics: univariate
National Institute for Alcohol Abuse and Alcoholism
Effect
DT vs no DT
Patients who developed DT compared with those who did not were significantly:
More likely to have a prior history of DT (56 vs 20%; p=0.05)

There were no significant differences between patients with a history of DT and those without on:
Standard drinks per drinking day (ns)
Drinking days in previous week (ns)
Previous inpatient detoxification (ns)
Brown ME, Anton RF, Malcolm R et al. Alcohol detoxification and withdrawal seizures: clinical support for a kindling hypothesis. Biological Psychiatry. 1988; 23(5):507–514. Ref ID: 251Retrospective case series 3−N=50Patients with documented alcohol withdrawal seizures

Setting: Alcohol detoxification unit, psychiatry unit, medical/surgical unit

Compared with patients admitted to an alcohol treatment program without seizure or neurological disorder

Patient population: The mean age of the withdrawal seizure group was significantly lower than the mena age of the control group (43 vs 49, p<0.05). There were significantly more whitr patients in the control group compared to the seizure group (76 vs 52%, p<0.05)
Alcohol withdrawal seizures
N=25

Treatment regimen: Oxazepam (64%). Schedule not specified
Without alcohol withdrawal seizures
N=25
NASeizures and: multiple detoxifications
History of drinking

Statistical analysis: Chisquare, t-tests, ANOVA
None reported
Effect
Seizure history vs no seizure history (control)
Significantly more patients with a history of withdrawal seizures had undergone five or more detoxifications compared to patients in the control group (12/25(48%) vs 3/25 (12%); p<0.05)

There was no significant difference between those patients with a history of seizures and the control patients on:
Alcohol use in the month prior to admission (ns)
Years of significant use (ns)
Age at which they first started drinking (ns)
Glenn SW, Parsons OA, Sinha R et al. The effects of repeated withdrawals from alcohol on the memory of male and female alcoholics. Alcohol & Alcoholism. 1988; 23(5):337–342. Ref ID: 240Prospective case series 3−N=143Patients with alcohol dependence/alcoholism who undergone detoxification three to six weeks prior to testing

Setting: Hospital affiliated and private treatment settings

Patient population: mean age 35 yrs, mean yrs of drinking 10, mean days drinking 239, mean typical quantity 367 g/day, mean typical quantity 0.06 g/kg
Treatment regimen: no details providedNANAAssociation between number of withdrawals and performance on memory and learning testsNone reported
Effect
There was a significant effect of the number of withdrawals on tests of immediate and delayed semantic and figural memory but not learning tasks (ns). The number of withdrawals was significantly correlated with:
  • Weschler Sematic Memory Test (Story B) immediate (0.221; p<0.01) and delayed (0.204; p<0.01)
  • Figural Memory sub-test I immediate (−0.181; p<0.05) Figural II immediate (−0.171; p<0.05)
  • Figural Memory sub-test II delayed (−0.144; p<0.01)
    Level 2++
There was no significant correlation between the number of withdrawals and:
  • Story A immediate and delayed (ns)
  • Figural delayed (ns)
  • Symbol-Digit paired associated (learning test) (ns)
  • Face-Name (learning test) (ns)
Lechtenberg R, Worner TM. Seizure risk with recurrent alcohol detoxification. Arch Neurol. 1990; 47(5):535–538. Ref ID: 1133Retrospective case series 3−

Univariate analysis
N=301Patients admitted for alcohol detoxification

Setting: Structured inpatient detoxification program

Exclusion critiera included: acute medical problems

Patient population: mean age 41 yrs, 64/301 antecedent seizure, mean alcohol consumption 292 g/daily, duration of alcohol use 24 yrs
Seizure history

Treatment regimen: chlodiazepoxide based on signs and symptoms
NASeizure history and previous detoxifications (documented in hospital records and by patient/carer report, no further definition supplied)

Statistical analysis: univariate
None reported
Effect
Incidence of seizures
There were no seizures in the current detoxification period

There was no significant association between a history of seizures and:
Age (ns)
Duration of alcohol abuse (ns)
Quantity of alcohol consumed (ns)
Wojnar M, Bizon Z, Wasilewski D. Assessment of the role of kindling in the pathogenesis of alcohol withdrawal seizures and delirium tremens. Alcoholism: Clinical & Experimental Research. 1999; 23(2):204–208. Ref ID: 1016Retrospective (N=892) and prospective (N=321) case series 3−N=1213Patients with alcohol withdrawal or delirium tremens (DSM-IV)

Setting: general psychiatric hospital

Exclusion: patients with concomitant substance dependence

Patient population: 82.9% male, aged 18 to 75 yrs mean 41 yrs
Treatment: Not reportedNASeverity of withdrawal (CIWA-A), incidence of delirium tremens, incidence of seizures

Statistics: ANOVA or non parametric equivalent (no covariates or regression analysis)
None reported
Effect
The proportion of patients according to age was:
< 30 yrs N=140, 30 to 39 yrs N=437, 40 to 49 yrs N=394, 50 to 59 yrs N=192, ≥ 60 N=50.
There was a significant difference in the age of onset of drinking (p<0.0001), duration of harmful drinking (p<0.0001) and average alcohol intake during the last drinking bout (p<0.05), according to age group. Older adults (≥ 60 yrs) started intensive drinking on average 11 yrs later than younger patients (< 30 yrs), but had drunk harmfully for a lot longer period of time (mean 18 yrs). The amount of alcohol comsumed in the last drinking bout was significantly lower as the patients’ age increased.
The mean CIWA-A score was 27
The mean incidence of delirium tremens was 26%
The mean incidence of withdrawal seizures was 4%
The mean daily dose of BZ was 51 mg (equivalent mg of diazepam)
The mean length of stay was 10 days

Factors associated with several withdrawal:
No significant associations were reported between age (< 30, 30 to 39, 40 to 49, 50 to 59 and ≥ 60 yrs) and:
The severity of alcohol withdrawal (CIWA-A score) (ns)
Incidence of delirium tremens (ns)
Incidence of withdrawal seizures (ns)
Mean daily BZ dose (ns)
Mean length of stay (ns)

From: Evidence Tables

Cover of Alcohol Use Disorders
Alcohol Use Disorders: Diagnosis and Clinical Management of Alcohol-Related Physical Complications [Internet].
NICE Clinical Guidelines, No. 100.
National Clinical Guideline Centre (UK).
Copyright © 2010, National Clinical Guidelines Centre.

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