European Journal of Cardiovascular Medicine

Alcohol use disorders (AUD) encompass a spectrum of disorders including excessive use, abuse, dependence and addiction ^[1]. Abuse occurs when a patient experiences adverse socioeconomic or health consequences related to the use of the substance ^[1]. Dependence is present either when the patient experiences withdrawal symptoms on discontinuation of the substance or when larger amounts are necessary to achieve the desired effect. Addiction is indicated by the patient experiencing a compulsive craving for a substance ^[1]. AUD are associated with a multitude of serious medical complications and known to cause systemic disorders. They may cause liver cirrhosis, pancreatitis, bone marrow suppression with resultant pancytopenia, dilated cardiomyopathy, hypertension, atrial fibrillation and renal dysfunction resulting in wasting of electrolytes such a potassium, magnesium and phosphorus ^[2].An estimated 76.3 million people worldwide have alcohol use disorders (AUDs) ^[3] and it is estimated that up to 42% of patients admitted to general hospitals, and one‐third of patients admitted to hospital intensive care units (ICU) have AUD ^[4].Alcohol withdrawal syndrome (AWS) is a well‐known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking, and it occurs in 8 to 40% of hospitalized AUD inpatients ^[5,6,7].Up to 50% of AUD patients experience withdrawal symptoms ^[8,9], a minority of whom requires medical treatment’s usually develops in alcohol-dependent patients within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. It is a potentially life-threatening condition whose severity ranges from mild/moderate forms characterized by tremors, nausea, anxiety, and depression, to severe forms characterized by hallucinations, seizures, delirium tremens and coma ^[6,10].The Diagnostic and Statistical Manual of Mental disorders (DSM-5) outlines diagnostic criteria for AWS using the two main components ^[11] first , a clear evidence of cessation or reduced in heavy and prolonged alcohol use second being the symptoms of withdrawal are not accounted by a medical or another mental or behavioural disorder. Magnesium is intimately involved in over 300 enzymatic reactions, particularly in the formation and utilization of ATP. Both acute and chronic alcohol intake can lead to a variety of electrolyte imbalances including hypomagnesemia ^[12]. Hypomagnesemia can occur in patients with alcohol abuse through reduced intestinal absorption, increased urinary losses, and intracellular shift of magnesium ^[13]. It occurs in up to 12% of hospitalized patients ^[14], and the incidence rises to high as 60 to 65% in patients in intensive care settings in which nutrition, diuretics, hypoalbuminemia, and aminoglycosides may play important roles ^[15,6,17]. Hypomagnesemia is common in alcoholic patients admitted to the hospital; as per literature, the prevalence was found to be as high as 30% ^[13]. As per a report published by Mayo Clinic, the risk of developing hypomagnesemia among people who excessively consume alcohol varies from 30% even up to 80% ^[18]. Hence this study was done to explore the relationship between hypomagnesemia and severity of   alcohol withdrawal syndrome.

Objectives:

1. To measure serum magnesium levels in chronic alcoholic patients who have abstained from alcohol for at least 6 hours
2. To estimate the severity of alcohol withdrawal symptoms and its relationship with serum magnesium levels.

The present study was a cross-sectional study done at: King George Hospital, Andhra Medical college, Vishakhapatnam from November 2022 to October 2023.

SAMPLE SIZE WITH JUSTIFICATION: Considering the prevalence of Hypomagnesemia in alcohol withdrawal patients as 29.9% ⁽¹³⁾

n= 4xPxQ/L2

P = 30%

Q = 70%

L = absolute precision of 10 %

n = 4×30×70/10X10= 84

The minimum sample size was 84 but this study included 100 patients

.

INCLUSION CRITERIA:

1. Male patients
2. Age >21 years
3. Patients exhibiting symptoms and signs consistent with Alcohol Withdrawal Syndrome (AWS) that meet the DSM-5 criteria for alcohol withdrawal syndrome.
4. Refraining from consuming alcoholic beverages for a minimum of 6 hours or more.

      EXCLUSION CRITERIA:

1. Patients with a history of other substance abuse, malabsorption syndrome or chronic renal failure, seizure disorder.
2. Patients with psychiatric illnesses that could cause hallucinations and Delirium, neurological conditions that predispose them to tremors,  nausea, and vomiting.
3. Patients taking magnesium supplements
4. Patients on diuretics.
5. Female patients with alcohol use disorder

STUDY TOOL: A predesigned and pretested questionnaire. The questionnaire includes demographic details of the patient, assessment of alcohol intake, Serum Magnesium estimation, smoking, past history (diabetes, hypertension), alcohol Withdrawal syndrome assessment.

Method of serum magnesium estimation:

• Serum magnesium levels were measured by direct colorimetric method with

Xylidin blue. The normal range is 1.7 to 2.3 mg/dL.

Alcohol withdrawal syndrome severity was assessed using CIWA-Ar (Clinical Institute     Withdrawal Assessment for Alcohol, revised) scale ^[19]

 It categorizes patients into levels of very mild, mild, modest, and severe withdrawal based on a ten-item scoring system. Each item scores from 0 to 7, except for orientation, which ranges from 0 to 4. The maximum total score is 67.

Scoring thresholds are as follows:

• Less than 10: Very mild withdrawal
• 10 to 15: Mild withdrawal
• 16 to 20: Modest withdrawal
• More than 20: Severe withdrawal

The CIWA-AR scoring domains:

1. Nausea and vomiting
2. Tremor
3. Paroxysmal sweats
4. Anxiety
5. Tactile disturbances
6. Auditory disturbances
7. Visual disturbances
8. Headache, fullness in head
9. Agitation
10. Orientation and clouding of sensorium.

A total of 100 participants were enrolled in this study. The mean age of the study participants is 40.86 ±11.28 years. Table1: shows demographic and various parameters in the study subjects. When considering age distribution highest number of subjects (28%) fall into the 31-40 years age group, followed by 41-50 years (26%). The smallest group consists of subjects older than 60 years, making up only 6%.  A significant majority, 67 subjects (67%), reported having a history of alcohol binge, whereas 33 subjects (33%) did not. The mean duration of alcohol consumption is 9.06 ± 4.55 years. Most subjects (45%) have been consuming alcohol for 10-15 years. This is followed by 30% of subjects who have been drinking for 5-10 years, and 20% for less than 5 years. Only 5% have been drinking for 15-20 years. It reveals that 13% of the participants are diabetic, while the remaining 87% are not. The study showed that 29% of the participants have hypertension, whereas 71% do not. Fifty seven percent of the patients in the study were found to be smokers and 43% are nonsmokers.

TABLE 1:  Distribution of participants based on various parameters

 Figure 1: Distribution of study subjects based on CIWA-Ar score. The mean CIWA Ar score is 24.89±13.19.

TABLE 2: Measurement of Magnesium for different CIWA-Ar score ranges. Analysis of variance (ANOVA) between CIWA-Ar Score and serum magnesium was done. p value was found to be significant.

TABLE 3: Comparison of CIWA-Ar Score and Serum Magnesium

TABLE 4: Correlation between CIWA-Ar score and duration of alcohol intake and serum magnesium levels

The above table show Pearson’s corelation coefficient between CIWA-Ar and various parameters. There is a positive correlation between CIWA-Ar scores and duration of alcohol intake and negative correlation between CIWA-Ar scores and serum magnesium. The correlation was found to be significant.

Figure 2: Scattered Plot Serum Magnesium Level & CIWA-AR Score

Figure 3: Scattered Plot Duration of Alcohol Intake & CIWA-AR Score

Figure: 5 Association of serum magnesium and CIWA -Ar score

Age distribution: In the present study, the age distribution of subjects revealed that highest proportion was in the 31-40 age group (28%), followed by the 41-50 age group (26%). The mean age of the study population was 40.86 years. Anitha Kumari et al ^[21] reported a similar mean age of 40.6 years, with the highest proportion (35%) in the 36-45 age group and 30% in the 46-55 age group. In comparison, Donogh et al  ^[20] found that 53% of their subjects were under 50 years old, with a mean age around the early forties. Consistent age distributions in these studies show that middle-aged adults are most affected by alcohol-related issues. This age group is crucial for targeted intervention and prevention

History of Alcohol Binge: 67% of the subjects from the present study were reported to have a history of alcohol binge drinking, while 33% did not. Although specific percentages were not provided in Sarai et al ^[22] study, the trend is consistent with findings. These studies reveal that many individuals with alcohol use disorders frequently engage in binge drinking.

Duration of Alcohol Consumption: The duration of alcohol consumption among subjects was categorized with the majority (45%) of consumed alcohol for 10-15 years. The mean duration of alcohol consumption was 9.06 years. Anitha Kumari et al ^[21] reported that 70% of their subjects had consumed alcohol for more than ten years

History of Smoking: 57% of the subjects reported a history of smoking. This high prevalence of smoking among individuals with alcohol use disorders is significant. Anitha Kumari et al ^[21] and Donogh et al ^[20] also reported a similar trend. Research indicates that smoking can intensify the rewarding effects of alcohol, making it difficult to quit both substances simultaneously. 

Diabetes: This prevalence of diabetes among individuals with alcohol use disorders is notable. This aligns with the general understanding of metabolic complications in individuals with alcohol use disorders. In the present study 13% of the subjects had diabetes.

Hypertension: Donogh et al ^[20] identified hypertension as a prevalent condition among their subjects In present study, nearly one-third of individuals with alcohol use disorders (29% )of the subjects had hypertension.

CIWA-Ar Score: A significant majority of subjects (58%) exhibited scores exceeding 20, indicative of severe withdrawal symptoms. The mean CIWA-Ar score was 24.89. Anitha Kumari et al ^[21]   reported significant withdrawal severity among their subjects. Donogh et al ^[20] also observed high CIWA-Ar scores, indicating severe alcohol withdrawal symptoms in a substantial proportion of their subjects.

CIWA-Ar Score with Serum Magnesium: In present study significant differences were observed in the serum magnesium levels across different CIWA-Ar score groups.Subjects with CIWA-Ar scores greater than 20 had significantly lower mean serum magnesium levels (0.72) compared to those with scores less than 10 (1.96), highlighting the biochemical disturbances associated with severe alcohol withdrawal. Anitha Kumari et al ^[21]  also examined similar associations between low magnesium levels and higher CIWA-Ar scores. Hypomagnesemia has been associated with more severe withdrawal symptoms and poorer outcomes.

Correlation between CIWA-Ar Score and Various Parameters: In this study, Pearson’s correlation coefficients were calculated to examine the relationship between CIWA-Ar scores and various parameters. There was a positive correlation between CIWA-Ar scores and the duration of alcohol intake (r = 0.464), and a negative correlation with serum magnesium (r = -0.802). These correlations suggest that longer alcohol consumption is associated with higher withdrawal severity, while higher levels of serum magnesium are associated with lower withdrawal severity. The study by Anitha Kumari et al ^[21] also found significant correlations between withdrawal severity and serum magnesium levels. Donogh et al ^[20] further highlighted the critical role of magnesium in influencing withdrawal severity and overall health outcomes in individuals with alcohol use disorders.

Comparison between Serum Magnesium Levels and CIWA-Ar Scores: Subjects with lower magnesium levels (<0.5) had significantly higher CIWA-Ar scores (mean 44.79) compared to those with higher magnesium levels (1.71-2.3, mean 10.95). This trend indicates that lower serum magnesium levels are strongly associated with more severe withdrawal symptoms. Study done by Stasyukinene et al ^[23] also revealed that hypomagnesemia occurs more frequently in severe alcohol withdrawal syndrome. Similar trends in serum magnesium levels and severity of alcohol withdrawal were seen in studies done by Prior et al ^[25] and Borah et al^[24].These findings highlight the critical role of magnesium in the pathophysiology of alcohol withdrawal. Hypomagnesemia can exacerbate withdrawal symptoms, increase the risk of complications such as seizures and delirium tremens, and negatively impact overall recovery.

The present study highlights the importance of intervention required in middle aged alcoholics and the need of integrated approach in patients with other behavioural risks like smoking and binge alcohol. The study also stresses over the patients with the history of long duration of alcohol intake, which is directly proportional to the severity of alcohol withdrawal syndrome. The strong correlation between high CIWA-Ar scores and low serum magnesium levels emphasizes the need of addressing and monitoring the magnesium levels during alcohol withdrawal syndrome. Over all, this study offers valuable insights for the future research studies prioritizing the integrated intervention strategies addressing the above biochemical abnormality for the better outcome in alcoholics with alcohol withdrawal syndrome.

Conflicts of interest: Nil

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