INTRODUCTION:

Alcohol consumption is often under-reported in patients admitted into hospitals. For alcohol-dependent individual’s hospital admission enforces period of abstinence which risks development of alcohol withdrawal symptoms. Some episodes of withdrawal symptoms are severe enough to require clinical attention.¹

Sudden withdrawal of chronic alcohol use can lead to changes with glutamate mediated CNS excitation, which can result in autonomic over activity.^2,3 The alcohol withdrawal syndrome is characterized by tremor, sweating, anxiety, agitation, depression, nausea, and malaise.⁴ It occurs 6-48 hours, after cessation of alcohol consumption and, when uncomplicated, abates after 2-5 days. It may be complicated by grand mal seizures and may progress to delirium (known as delirium tremens),⁵ which may be seen in as high as 15% alcohol use disorder patients.^2,6

Organ damage and gut leakage are the major health risks involved with binge alcohol consumption. Chronic consumption of alcohol also effects the gut microbiota, leads to gut leakage with high endotoxins which may lead to liver disease and hepatocellular carcinoma.^7,8 There are more than 200 diseases to which alcohol contribute, in addition to liver diseases, including alcoholic dementia, falls and automobile accidents, injury, cancer etc.^9,10,¹¹ High alcohol intake negatively alters brain function^12,13 and it can cause various mental diseases including anxiety, mood disorders, sleep disturbances, psychotic syndrome and dementia.^14,15,16

Most of the patients show severe withdrawal symptoms which require clinical attention. Benzodiazepines forms the base of treatment in these circumstances.^4,17 Ideal Benzodiazepine must have a rapid onset, wide margin of action, longer duration of action, an independent metabolism in liver function, and should not have any abuse potential.⁴ They are proven to decrease the severity of withdrawal symptoms, and its incidence of seizures and delirium tremens. ^4,18,19 Anticonvulsants are not proven to be better than Benzodiazepines, but used sometimes in the mild withdrawal state, due to some advantages like lower chances of sedation and dependence or abuse.³ This study hopes to assess the duration and severity of alcohol withdrawal syndrome and evaluate the efficacy of different types of Benzodiazepines in the management.

Experimental:

A prospective observational study was carried out for a period of eight months at the de-addiction centre attached to Psychiatry department of a tertiary care teaching hospital. Patients aged 18 years and above, admitted in psychiatry de-addiction ward, and who are willing to participate in the study were included, and patients diagnosed with psychosis, severe medical illness or injuries and patients with other substance abuse (except nicotine) were excluded from the study. A total of 220 patients, who met the inclusion and exclusion criteria were included for the study. Each patient’s socio-demographic details were recorded. On first day of admission AUDIT score (“Calculator: Alcohol consumption screening AUDIT questionnaire in adults,” n.d.) is taken to assess alcohol use. Then followed by CIWA-Ar questionnaire ²⁰ done on Day-1, Day-3, Day-5, Day-7 and Day-10, to detect symptoms of alcohol withdrawal. In addition, SGOT and SGPT levels are observed from individual patient case notes and patient profile forms. The study assesses the efficacy of different types and doses of Benzodiazepines in reducing the severity of alcohol withdrawal syndrome. Concludes that the treatment must be individualized with the help of rating scale.

RESULTS

Demographic details of study population.

Distribution of subjects according to their age and gender.

Among 220 patients, 216 were males (98.18%) and 4 were females (1.82%). The age wise distribution of subjects was also observed, majority of the subjects belonged to the age group of 40-49 years (33.18%). The age of the study population ranged from 18-73 years, mean age being 41.28 ± 10.85 years.

Distribution of subjects according to their body weight.

Most patients body weight ranged between 61kg to 70kg (88; 40%), followed by >70 Kg, 79 (36%) patients. The body weight of subjects ranged from 41-82 Kg with a mean value of 60.09 ± 8.41 kg.

Distribution of subjects according to their social habit.

Out of 220 in-patients, 118 (53.636%) patients reported of alcohol, and tobacco consumption. Whereas the remaining 102 (46.363%) patients only consumed alcohol.

Distribution of subjects according to the length of hospital stay:

Among 220 patients, majority of the patients 102 (46.363%) were admitted in the hospital for a period of 11-20 days. The length of hospital stays of the patients ranged from 03-53 days with mean value of 19.868 ± 11.54 days.

Distribution of subjects based on their AUDIT score.

In the study, Among total of 220 patients. Majority of the patients were observed to have an AUDIT score between 25-32, followed by 90 of them with a score between 17-24. Their mean AUDIT score was of 25.78 ± 5.46. The distribution of the subjects based on their AUDIT score has been illustrated in Figure 1.

Figure 1: Distribution of subjects based on their AUDIT score.

Distribution of subjects based on their severity assessment (CIWA-Ar score).

CIWA-Ar was administered on day one, three, five, seven and day ten. A gradual decrease of signs and symptoms in each patient were observed. On day-1, 100 subjects showed a moderate signs and symptoms (CIWA-Ar score = 9-20) followed by 96 subjects showed severe symptoms (CIWA-Ar score = >20) and on Day 10 majority of the subjects showed mild signs and symptoms (CIWA-Ar score = < )8. The symptoms eventually subsided in 5-7 days. Distribution of the severity assessment has been illustrated in the figure 2.

Figure 2: Distribution of subjects based on their severity assessment (CIWA-Ar score).

Correlation between SGOT, SGPT and severity of AWS:

Out of 220 patients 64 of them had normal levels of SGOT and 156 were abnormal. 110 patient had normal SGPT levels and 110 were abnormal. There was no significant correlation between SGOT, SGPT and the severity of alcohol withdrawal syndrome. Correlation between SGOT, SGPT and severity of Alcohol withdrawal symptom is illustrated in Table 1.

Table 1: Correlation between SGOT, SGPT and severity of AWS.

	*CIWA-Ar*	*SGOT*	*SGPT*
CIWA-Ar	1	-	-
SGOT	0.208691	1	-
SGPT	0.007377	0.601421	1

Distribution of subjects based on Thiamine prescribed.

The dose of Thiamine prescribed varied from 100-600mg among the patients. Majority of the patients were prescribed with parenteral Thiamin 100mg from the time of admission. The distribution of the subjects based on Thiamine prescribed has been illustrated in the Table 2.

Table 2: Distribution of subjects based on Thiamine prescribed.

Thiamin (Day 1)	No: Patients
100mg	63
200mg	14
300mg	128
600mg	15
Thiamin (Day 7)	No: Patients
100mg	157
200mg	21
300mg	42
600mg	0
Thiamin (Day 5)	No: Patients
100mg	117
200mg	21
300mg	80
600mg	2
Thiamin (Day 10)	No: Patients
100mg	176
200mg	12
300mg	32
600mg	0
Thiamin (Day 3)	No: Patients
100mg	62
200mg	14
300mg	130
600mg	14

Distribution of Benzodiazepine:

All 220 patients were prescribed with a Benzodiazepine. Majority of the 135 (61.36%) patients were given an intermediate-acting Benzodiazepine – Lorazepam. 85 (38.63%) received long acting Benzodiazepine- Diazepam and chlordiazepoxide.

Distribution of Benzodiazepine based on the severity of AWS.

Based on CIWA-Ar score, the severity of AWS was quantified, and the prescription of Benzodiazepine based on the severity of AWS was observed and to monitor and treat patients according to their symptoms. The study showed that patients with mild-moderate withdrawal symptoms were often prescribed with Lorazepam and most of the patients with moderate-severe withdrawal symptoms are prescribed with Diazepam (table 3).

Table 3: Distribution of Benzodiazepine based on the severity of AWS.

Ciwa-Ar Score (Day1)	No: Patients Lorazepam Diazepam
Mild (< =8)	23	15	8
Moderate (9-20)	100	61	39
Severe (<20)	97	42	55
Total	220	118	102
CIEA-Ar Score (day3)	No: Patients Lorazepam Diazepam
Mild (<=)	23	13	10
Moderate (9-20)	106	61	45
Severe (>20)	91	42	49
Total	220	127	93
CIWA-ArScore (Day 5)	No: Patients Lorazepam Diazepam
Mild (< = 8)	81	50	31
Moderate (9-20)	133	73	60
Severe (>20)	6	4	2
Total	220	127	93
CIea-ArScore (Day 7)	No: Patients Lorazepam Diazepam
Mild (< = 8)	170	109	61
Moderate (9-20)	50	24	26
Severe (>20)	0	0	0
Total	220	133	87
CIWA-Ar Score (Day 10)	No: Patients Lorazepam Diazepam
Mild (< = 8)	210	146	65
Moderate (9-20)	10	4	6
Severe (>20)	0	0	0
Total	220	150	71

DISCUSSION:

Benzodiazepine are the cornerstone in the treatment of alcohol withdrawal syndrome.^21,22 This study demonstrates the utility of different Benzodiazepine in alcohol detoxification with the aid of severity scale. Patients with continued excessive alcohol consumption are at greater risk of having withdrawal symptoms for a longer period compared to those with a lower consumption rate.^23,24

The current study which included 220 patients, showed that the percentage of male patients (98.18%) were more, compared to the female patients (1.81%). Similar result was obtained in other studies.^25,26 Another study showed contradicting results wherein the number of females were more, compared to the males.^27,28

The majority of patients who received Benzodiazepine for AWS treatment in the de-addiction ward belonged to the age group of 40-49 years (33.18%). The age of the study population ranged from 18-73 years with average age of 41 years. Similar results were observed in other studies ²⁵, in a different report,²⁹ age, year median was 49. Our study was inconsistent with the result of the study conducted by Dolman and Hawkes²⁷, which showed an average age of 61.70.

AUDIT screening alerts the clinicians of a possible alcohol misuse and help to individualize the initial dose accordingly for each patient.^30,31 In our study, a total of 220 patients admitted in the de-addiction ward were screened with AUDIT on the first day of admission. All the subjects showed AUDIT score 8 or more indicating alcohol use disorder. Majority of the patients were observed to have an AUDIT score between 25-32, followed by 90 of them with a score between 17-24. Similarly, in another study, all patients were initially screened on the first day of admission for alcohol use using AUDIT.²⁶ The study done by Dolman and Hawkes²⁷, had AUDIT mean score of 5.74. No patient with an AUDIT score less than 8 experienced any clinical significant alcohol withdrawal.

The risk of alcohol withdrawal syndromes like seizures and delirium tremens are higher during the first phase of the admission. Patient requires to be monitoring to prevent further complication. CIWA-Ar is important to diagnose and start an adequate treatment. In our study each patient’s symptoms severity assessment was done every alternate day of the 1^st 10 days from admission. On day1, 3 and 5 majority of the patients experience moderate withdrawal symptoms. By day 7 and day 10 most of them had mild withdrawal symptoms. Doses of Benzodiazepine was given based upon the score obtained on CIWA-Ar, even though CIWA-Ar is done. Patients were observed closely for any psychiatric symptoms which may mimic AWS, as is the case described earlier.³²

A recently published article³³, concluded that the AUDIT scale should be explored alone and to improve screening for clinical AWS it should be used in combination with other parameters. Our study showed no significant correlation between SGOT, SGPT and the severity of alcohol withdrawal. Similarly, Lee et al.³⁴ demonstrated that even non-drinkers with healthy liver apparently have similar levels of SGOT, SGPT and GGT. A significant relation between elevated levels of SGOT, SGPT, SGOT/SGPT ratio and alcohol related seizures has been described earlier.^35,36

In this study the efficacy of different types of Benzodiazepine were monitored. The most often prescribed Benzodiazepine was Lorazepam, an intermediate acting agent, followed by diazepam a short acting agent. Studies conducted by Mirijello et al.,²¹, Amato et al.,³⁷, Mainerova et al.,³⁸ preferred short acting benzodiazepines (e.g. Lorazepam, Midazolam and Oxazepam). Whereas, in the study conducted by Muzyk et al.,³⁹, Ntais et al.,³² concluded that long- acting agents (Diazepam and Chlordiazepoxide) having the ability to produce a smoother withdrawal is an effective treatment option for hospitalized patients with AWS.

The dosing of Benzodiazepine was guided by withdrawal symptom’s severity. BZD was only given when the CIWA-Ar score was above 8. The medication was tapered off within 5-7 days. Eventually the medication is stopped when the CIWA-Ar score decrease to less than 8. This practice was in consistence with literature. ^40,41

In this study Thiamine was routinely prescribed to all patient throughout the first 10 days of admission. Administration of parenteral Thiamin provides adequate blood thiamine level much faster than the other route to prevent from complication like Korsokoff’s encephalopathy, Wernicke’s encephalopathy.^42,43 Another study⁴⁴ concluded that all patients must be prescribed at least with 250mg thiamine via parenteral route once daily, for the first 3-5 days of admission.

CONCLUSION:

This study concludes that Lorazepam is the most commonly prescribed benzodiazepine in the treatment of alcohol withdrawal syndrome. Even though both Lorazepam and Diazepam are equally effective Benzodiazepines, the choices of drugs differ from each patient. It is variable and patient specific. Thorough monitoring and adequate treatment of withdrawal symptoms is the best way to prevent severe complications. The treatment works best when it is individualized with the help of rating scales. A perfect detoxification at the beginning of admission can reduce the future severity and relapse of AWS. This will help motivate patient to abstain from drinking.

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Received on 10.08.2021 Modified on 19.01.2022

Research J. Pharm. and Tech 2022; 15(11):5321-5326.

DOI: 10.52711/0974-360X.2022.00896