
 alcohol withdrawal syndrome ( aws ) is characterized by varied symptoms that range from mild to severe intensity depending on several factors including the quantity , frequency and duration of alcohol intake , and the number of prior withdrawal episodes , as well as individual differences in the vulnerability [ 14 ] .
symptoms usually present themselves within 6 to 24 hours after cessation of alcohol intake [ 5 , 6 ] .
subtyping of the aws has been attempted in the past , as gross   conceptualized and proposed 3 constellations of alcohol withdrawal symptoms : factor 1 hallucinogenic that consisted of nausea , tinnitus , visual disturbance , pruritus , parasthesia , muscle pain , agitation , sleep disturbance , tactile hallucinations , and hallucinations which are auditory or visual or both ; factor 2 affective and physiological that consisted of anxiety , depression , tremor , and sweats ; and factor 3 delirium that consisted of clouding of the sensorium , impairment of consciousness , and impairment of contact with the observer .
a cluster analytic study   identified three different symptoms clusters of alcohol withdrawal , namely , cns excitation , adrenergic hyperactivity , and delirium .
several rating instruments have been used to measure severity of alcohol withdrawal . among them ,
the most commonly used observer - rated scale is the 10-item clinical institute withdrawal assessment - alcohol , revised ( ciwa - ar ) .
it has been proposed that alcohol withdrawal symptoms in ciwa - ar appear multidimensional . a pubmed search supplemented with
the study by pittman et al .   was to explore the relationship between awsc and ciwa - ar , for which they carried out study on 127 male inpatients of alcohol dependence with principle components factor extraction with varimax rotation of ciwa - ar , a self - rated  alcohol withdrawal symptoms checklist ( awsc ) and on combined items of ciwa - ar and awsc .
they found three , five , and seven factor solution , respectively , for ciwa - ar , awsc , and combination of ciwa - ar and awsc .
the analysis of ciwa - ar was done on 7 items as 3 items had zero variance . the first factor ( variance 23.9% ) was  tension / anxiety  which consisted of anxiety , agitation , and tactile disturbances . the second factor ( variance 22.9% ) was  autonomic arousal  which consisted of paroxysmal sweats , tremor , and headache or fullness in head , whereas the third factor ( variance 17.4% , eigenvalue less than 1 ) was  nausea and vomiting  which consisted of a single item , nausea , and vomiting . in our setup
, we use ciwa - ar as part of the measure for the management of alcohol withdrawal symptoms .
it is generally observed that alcohol withdrawal symptoms fluctuate in presentation and severity across time .
the present study was carried out to explore the dimensionality of this scale in an attempt to identify a set of underlying factors that exist and can explain the interrelationships among various manifestations of acute alcohol withdrawal symptoms .
the knowledge of these underlying factors may enhance our understanding of aws and better prediction of complications thus management plans .
this was a cross - sectional hospital - based study , conducted at centre for addiction psychiatry , central institute of psychiatry , ranchi , india , a tertiary care referral centre during may 2005 to june 2006 .
study sample included 201 , only male fulfilling icd-10 dcr ( world health organization )   for alcohol dependence with currently withdrawal state , aged between 18 and 60 years , admitted within 24 hours of abstinence and patient himself or his guardian consenting for the study .
information on patient 's demographics , treatment history , past history , and family history was obtained from interviews with patients and accompanying person .
detailed physical and neurological examinations were done to exclude any comorbid general medical condition , comorbid other psychiatric disorder , and any other comorbid substance use disorders except caffeine and tobacco . 

the sociodemographic data sheet included age , marital status , religion , community , education , and economic status . whereas clinical variables recorded were age of onset of drinking alcohol , duration of dependence , past history of detoxification , number of previous detoxification , past history of withdrawal seizure , past history of delirium tremens , family history of alcohol or substance dependence , degree of relationship if family history of alcohol or substance dependence is present , and family history of mental illness .  

it is the most widely used and studied 10-item alcohol withdrawal monitoring scale , which excludes vital sign abnormalities .
it was developed from the 18-item clinical institute withdrawal assessment for alcohol and it has been studied across various geographic locations .
it has a good reliability , validity , and it is considered as one of the most widely used alcohol withdrawal assessment scale for symptom - triggered therapy .
each sign and symptom item of ciwa ar is evaluated on a 07 point likert scale except for one item  orientation and clouding of sensorium  , which is scored on a 04 point likert scale .
a score of 8 points or less indicates mild withdrawal and patients scoring less than 10 do not usually need additional medication for withdrawal .
patients admitted with alcohol dependence syndrome with acute withdrawal were evaluated with ciwa - ar immediately after admission then every six hours , as a routine protocol of the ward .
detailed physical examination , mental status examination , and planned screening laboratory investigation were done to ensure conformity of study criteria .
the patients get admitted with varying lengths of abstinence , ranging from hours to days , so we initially took all the ratings of all the patients and arranged them as rating at first 6 hours of abstinence and at every six hours like at 6 , 12 , 18 , 24 , 30 , 36 , 42 , 48 , 52 , 58 , and 64 hours till ciwa - ar scoring reaches below 10 .
the averages of each rating of ciwa - ar scores were computed to see the severity of withdrawal symptoms across time span of abstinence .
many patients were admitted after overnight , 12 to 18 hours of abstinence , so we included the patients who were admitted with at least 24 hours of abstinence .
meanwhile management and medications were continued as per ward protocol and no adjustment for study purpose was done .
the standard detoxification protocol included thiamine supplementation , benzodiazepines either lorazepam or diazepam , and correction of fluids and electrolytes if any and other symptomatic treatment of associated conditions like dyspepsia or concurrent injury , wound , and infections .
the collected data on 201 patients was statistically analyzed , using statistical package for social sciences ( spss , inc . ,
exploratory factor analysis ( maximum likelihood method ) was carried out to identify factor structure on all items of ciwa - ar for day three .
kaiser - meyer - olkin measure of sample adequacy and bartlett 's test of sphericity were also done to assess appropriateness of conducting factor analysis .
two criteria for retaining the number of components were considered : kaiser 's criterion   to retain eigenvalues greater than unity and cattell 's   scree plot inspection for the point of inflexion .
the mean age of the group was 37.18 ( sd 9.35 , range 1869 ) years .
most of them were married ( 83.3% ) , educated ( 90% ) , residing in urban background ( 64.7% ) , belonging to middle socioeconomic status ( 60.3% ) , and earning a livelihood ( 80.4% ) .
the mean age of starting alcohol was 21.63 ( sd 4.99 ) years , whereas mean duration of dependence on alcohol was 6.49 ( sd 5.06 ) years .
22.5% had history of withdrawal seizures , in their course of alcoholism , and only 2% reported history of delirium tremens in the past .
family history of substance dependence was present in 33.3% of the total sample , out of which alcohol dependence was present in 56.9% of subjects and cannabis dependence in 8.3% .
the item frequency and mean of all six hourly ciwa - ar ratings were calculated ; the mean scores of ciwa - ar at 24 hours and at 36 hours are shown in table 2 .
the mean ciwa - ar score at 24 hours was 13.32 ( sd 9.27 ) and 20.4 ( sd 9.09 ) at 36 hours .
based on the frequency variance and total ciwa - ar score we decided to carry out factor analysis with the 10 items of ciwa - ar as on scoring at 36 hours of abstinence .
bartlett 's test of sphericity was significant ( 2 = 1.044 , df = 45 , p < .001 ) , indicating that a factor analysis is appropriate .
factor analysis ( extraction method - maximum likelihood ) with the 10 items of ciwa - ar for day three , resulted in initial three factors with eigenvalues greater than unity .
the scree plot was also showing clear inflexion , supporting three factors ( figure 1 ) .
therefore , three factors were retained , which captured 68.74% of variance . following varimax rotation with kaiser 's standardization ,
the factors and their item loadings , with absolute values greater than 0.1 , are shown in table 3 .
none of the items loaded on more than one factor . the first factor named as 
delirious factor ,  which had highest loading from tactile disturbances ( .999 ) , followed by auditory disturbances , orientation and clouding of sensorium , and agitation .
it explained 34.34% of variance and showed good internal consistency ( cronbach 's alpha = .91 ) . the second factor named as 
autonomic factor  reflected four - item loading , highest from anxiety , followed by paroxysmal sweats , tremor , and headache or fullness in head .
it explained 24.25% of variance and showed moderate internal consistency ( cronbach 's alpha = .66 ) . the third factor named as 
nonspecific factor  reflected two - item loadings , nausea , and visual disturbances that explained 10.04% of variance and a cronbach 's alpha of .26 .
we examined the factor structure of the ciwa - ar in a population of adult men hospitalized to a tertiary psychiatric institute for treatment of alcohol dependence .
the ideal study of aws could have been the assessment before starting medication , but this was practically not possible for many reasons .
firstly , many of the patients come for admission after 12 to 18 hours of abstinence and severe withdrawal , so keeping them drug free was ethically not possible .
thus natural aws presentation and its severity were masked by routine benzodiazepam administration and thiamine supplement .
secondly , many other patients were referred from primary care centers with initial management , including long acting benzodiazepines like diazepam that masks the aws .
thirdly , many other patients came even before onset of withdrawal and in a state of intoxication ; the aws was not fully evolved in terms of range of symptoms and severity .
for all these reasons , the mean ciwa - ar score for the initial 24 hours of abstinence ( first day ) of admission was only 13.32 ( sd 9.27 ) .
later the sequential rating found more prominent withdrawal symptoms reaching highest mean score of 20.4 at thirty - six hours then gradually decreased .
as drug free aws was not possible , we consider that the higher mean score of ciwa - ar represents the aws better than low score . also as both aws medications and alcohol itself are cns depressant and act in a similar way , either medication or alcohol intake should not make much difference in clinical picture .
so we decided to proceed for factor analysis with highest mean ciwa - ar scoring at the 36th hour .
the severity of withdrawal symptoms and appearance of complete sets of withdrawal symptoms at the 36th hour may have been influenced by plasma half - life of benzodiazepams being used for detoxification . in this study ,
choice of medication was with treating team of the hospital ; however , only either intermediate acting lorazepam or long acting diazepam was used for this purpose .
there was no use of short acting benzodiazepines , which causes varying and rebound withdrawal symptoms across different time frame with its dosing and changing plasma concentration .
another more important influencing reason for varying withdrawal symptoms across different time frame could have been the dose of benzodiazepines , but we did not interfered with any medications or dosing and it was continued as per ward protocol to ensure naturalistic conditions . however , the equivalent benzodiazepines mean dose at 36 hour was 30  mg of diazepam per day .
but this equivalent dose may not be accurate as many patients were on oral medications and others were on parenteral benzodiazepines .
we excluded any other comorbid substance use disorders or polysubstance dependence but a few patients may also have undisclosed benzodiazepine or organic inhalant abuse or addiction .
we also excluded any comorbid general medical condition especially epilepsy for that reason , patients on antiepileptic either taking it regularly or skipping will modify the alcohol withdrawal symptoms . for
that matter any psychotropic drugs causing cns depression or any effecting stimulants will alter the withdrawal symptoms .
most of the patients needed proton pump inhibitor drugs like pantoprazole or omeprazole for the alcohol induced dyspepsia , peptic ulcer disease , or gastroesophageal reflux disease , but these medications do not impose any effect on alcohol withdrawal symptoms . in a previous study by pittman et al . , the mean ciwa - ar score for day one was 13.2 ( sd 3.7 ) which was similar to our study , 13.32 ( sd 9.27 ) at 24 hours ; they continued with analysis on data collected on the first study day to exclude medication effects .
but we analyzed the data as of 36 hours of abstinence , showing higher mean ciwa - ar score and all ten items had variance above 10% , thus representing fully developed withdrawal syndrome .
however we could not control the medication effect used to control the withdrawal symptoms for ethical reasons , the used medications were benzodiazepine and thiamine supplementation for all the patients .
two items of ciwa - ar , namely , auditory disturbances and tactile disturbances were very infrequent in our sample ( 9.5 and 10% ) on day one which increased to 55.1 and 65.7% at 36 hours , other items scoring raised on day two like agitation , orientation and clouding of sensorium , visual disturbances , and paroxysmal sweats ; few other items remained unchanged on day one and two like anxiety and tremor ; however scoring of only this item  headache or fullness in head  improved on day two from 28.9 to 12.9% ( table 2 ) .
this indicates the importance of time duration of abstinence to study the alcohol withdrawal symptoms .
we found a three - factor solution based on rotated eigenvalues and scree plot analysis .
the first factor explained 34.34% variance and consisted of four items , namely , tactile disturbances , auditory disturbances , orientation and clouding of sensorium , and agitation .
this factor appears to represent perceptual abnormality and delirium and may be considered as subclinical spectrum of delirium .
however , the only other factor analytic study of ciwa - ar by pittman et al .   found these items ( except agitation ) were infrequent in their sample and were not included in analysis .
the difference may be due to the time span of withdrawal on which data was collected .
study analyzed ciwa - ar for day one and also our data on day one showed very low variance for these items .
this suggests that ratings on alcohol withdrawal symptoms on the very first day may miss certain set of symptoms , which appears on and around day two and are characterized by perceptual abnormality and delirium like picture .
further progression of alcohol withdrawal , we could not found beyond 36 hours , may be due to effects of continued medications for withdrawal suppression .
surprisingly , visual disturbances item did not have high loading on this factor , whereas tactile and auditory disturbances had maximum factor loading ( 0.999 and 0.873 , resp . ) .
the etiological basis for these two disturbances includes cns rebound excitation which alters the perceptual quality .
furthermore , some contribution of nutritional and specific vitamin deficiencies , such as thiamine and folate , and associated peripheral neuropathy probably add to these perceptual disturbances .
the other two items , orientation and clouding of sensorium and agitation with factor loadings of 0.851 and 0.777 , respectively , represent delirium .
the perceptual alteration and delirium being loaded in a single factor may have some predictive association and hence need to be studied for management plan .
the second  autonomic  factor explained 24.25% of variance and consisted of four items : anxiety , paroxysmal sweats , tremor , and headache and fullness in head with factor scores of .998 , .660 , .528 , and .245 respectively .
cronbach 's alpha for this factor was 0.66 showing adequate internal consistency . within this factor
this factor may be a result of the practice of not using adrenergic medication on routine basis at our institute .
all items ( paroxysmal sweats , tremor , and headache or fullness in head ) were loaded similarly .
we had additional anxiety to this factor ; hence , we share the name of this factor with pittman et al .   as  autonomic  .
the third  nonspecific  factor explained 10.04% of variance and consisted of two items : nausea and vomiting and visual disturbances , with low factor scores of .51 and .27 , respectively .
there are three proposed physiologic bases for the symptom manifestation of alcohol withdrawal symptoms : cns excitation , adrenergic hyperactivity , and delirium , which may be attributed to different neurotransmitters and they respond selectively to different pharmacotherapy
. the cns excitation may be secondary to deficiency in gaba activity , whereas increase in cns epinephrine level causes adrenergic hyperactivity .
the nmda receptor hypersensitivity and overactivity of certain subtypes of nmda receptors are associated with delirium .
though we did not find a factor structure of aws in accordance with very strict pathophysiological manifestation of either autonomic , or cns excitation or psychological / affective , or perceptual / hallucinogenic in our sample , the obtained factors suggest existence of subgroups of patients with different set of symptoms .
this was expected as alcohol withdrawal manifests by simultaneous involvement of all mechanisms rather than any mutually exclusive mechanism .
this simultaneous involvement of several other neurotransmitters besides gaba and nmda , like noradrenaline , acetylcholine , and dopamine as well as hormones and electrolytes [ 17 , 18 ] will affect the symptom presentation .
additionally our data analysis had ciwa - ar ratings of day two ( 36 hours ) of admission with suppression of withdrawal symptoms from detoxification medications , that is , benzodiazepines .
this would have differential effect on withdrawal symptoms manifestation in terms of gaba suppression only and selective unopposed action on other neurotransmitters or lacking adrenergic activity . though avoiding pharmacological suppression or modification was not possible on ethical grounds to understand completely natural unmodified withdrawal manifestation .
there may also be possible influence of different types of alcoholic beverage and percent content of alcohol .
strength of our study includes large sample size and not interfering with any medications or management strategies thus providing setting of naturalistic conditions .
the use ciwa - ar is the most widely accepted alcohol withdrawal assessment scale and selection of abstinent hours was important to allow time for full appearance of symptoms , even though under cover of detoxification medication .
there was for better coverage and inclusion of withdrawal symptoms at 36 hours as indicated by total ciwa - ar score and item frequency .
these results have wider implications for the recognition and management of aws , particularly , for better understanding and identification of the symptom profiles for and differential management plans across subtypes of aws .
the use of adrenergic antagonists may have a valuable role in addition to benzodiazepines , in a set of patients with autonomic features .
one of the limitations in our study is that it includes male only patients ; however , gender can be an important issue in aws presentation and its severity .
even studies found that sex hormone affects the aws by modulating the function of the gaba - a receptor .
also low levels of testosterone are associated with symptoms like indecision , excessive worrying , fatigability , and lassitude .
another limitation of this study is patients sample with severe aws requiring inpatient management , thus limiting generalizability of our findings across gender and to mild to moderate severity cases .
another limitation was that diagnosis was made clinically with icd-10 dcr criteria for  alcohol dependence with currently withdrawal state  , but not by a validated clinical interview .
it is known that autonomic arousal is an important mechanism in aws ; thus , other physiological measures and biological markers for objective assessment may be included in future studies .
further studies may also be carried out including cases of mild to moderate severity and in both sex to uncover the differences .
also , factor analysis depends heavily on the population studied ; therefore , studies on different population may be required to generalize our findings . for the clinical practice ,
it is advisable not to overdepend on rating scales and it must not replace a thorough clinical evaluation of the patient 's medical status in prediction of those at risk of severe alcohol withdrawal .
the acute alcohol withdrawal symptoms was most severe at 36 hours of abstinence in our sample .
this study finds multidimensionality of alcohol withdrawal symptoms as measured with ciwa - ar ; we found three factors explaining 68.74 percentage of variance and named as delirious , autonomic and nonspecific .
 
 objective . to identify the underlying factor structure of alcohol withdrawal syndrome , as measured with ciwa - ar 
 . methods . 
 exploratory factor analysis was conducted on the items of ciwa - ar . on 201 alcohol - dependent male patients seeking treatment for alcohol withdrawal at 36 hours of abstinence . 
 results . 
 a three - factor solution was obtained that accounted for 68.74% of total variance . 
 first factor had loading from four items ( 34.34% variance ) , second factor also had four items ( 24.25% variance ) , and the third had two items ( 10.04% variance ) . 
 conclusions . factor analysis reveals the existence of multidimensionality of alcohol withdrawal as measured with ciwa - ar and we found three factors that can be named as delirious , autonomic and nonspecific factors . 
1. Introduction
2. Materials and Methods 
3. Results 
4. Discussion 
5. Conclusion