|Year : 2021 | Volume
| Issue : 1 | Page : 63-67
Study of relationship between serum creatine phosphokinase levels with severity of alcohol withdrawal
Rani Malik1, Harpreet Singh Dhillon2, Vinod Kumar Sahu3, Shibu Sasidharan4, Gurpreet Kaur Dhillon5
1 Assistant Professor, Department of Psychiatry, Naval Hospital, Vishakhapatnam, Andhra Pradesh, India
2 Assistant Professor, Department of Psychiatry, IFH Level III Hospital MONUSCO, Goma, DRC
3 Assistant Professor Psychiatry, People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India
4 Assistant Professor, Department of Anaesthesiology and Critical Care, IFH Level III Hospital MONUSCO, Goma, DRC
5 Assistant Professor, Department of Paediatrics, Military Hospital, Jammu, India
|Date of Submission||12-Jan-2021|
|Date of Acceptance||01-Mar-2021|
|Date of Web Publication||01-Jun-2021|
Dr. Harpreet Singh Dhillon
Department of Psychiatry, Level III Hospital, Goma
Source of Support: None, Conflict of Interest: None
Background: Alcohol withdrawal syndrome is a potentially life-threatening condition with severe complications such as withdrawal seizures and delirium tremens. A valid and reliable biomarker for predicting the severity of alcohol withdrawal can be instrumental in individualizing effective therapy at the earliest.
Methodology: This was an observational study done on 120 patients to study the relationship between serum creatine phosphokinase (CPK) levels with severity of alcohol withdrawal. The assessment for the severity of alcohol withdrawal was done with Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale and an association was studied between the serum CPK levels and the severity of alcohol withdrawal. The data was analyzed using Chi-square test and Kruskal–Wallis tests.
Results: The severity of alcohol withdrawal as per the CIWA was 26.66% mild, 55% moderate, and 18.33% severe. The mean serum CPK level for mild withdrawal was 126.93 IU/L, moderate withdrawal was 303.66 IU/L, and for severe withdrawal was 780.81 IU/L. A statistically significant association was obtained indicating that patients with higher CIWA-Ar scores are likely to have a higher level of serum CPK levels.
Conclusion: Serum CPK levels were significantly associated with severity of alcohol withdrawal and can possibly serve as a candidate biomarker.
Keywords: Alcohol biomarker, alcohol withdrawal syndrome, Clinical Institute Withdrawal Assessment for Alcohol-revised, creatine phosphokinase
|How to cite this article:|
Malik R, Dhillon HS, Sahu VK, Sasidharan S, Dhillon GK. Study of relationship between serum creatine phosphokinase levels with severity of alcohol withdrawal. Arch Ment Health 2021;22:63-7
|How to cite this URL:|
Malik R, Dhillon HS, Sahu VK, Sasidharan S, Dhillon GK. Study of relationship between serum creatine phosphokinase levels with severity of alcohol withdrawal. Arch Ment Health [serial online] 2021 [cited 2021 Nov 28];22:63-7. Available from: https://www.amhonline.org/text.asp?2021/22/1/63/317421
| Introduction|| |
Alcohol dependence syndrome is a major public health problem impacting social, psychological, medical, economic, and religious spheres of our existence. The National Household Survey of Drug Use in India reported the prevalence of alcohol consumption (21.4%) as the primary substance used (apart from tobacco) followed by cannabis (3.0%) and opioids (0.7%). The effects of chronic heavy use of alcohol lead to damage to almost all the organs including esophagus, stomach, liver, pancreas, heart, brain and sexual dysfunction. In addition to the above complications, alcohol withdrawal syndrome is a potentially life-threatening condition with a spectrum of symptoms ranging from mild insomnia and tremulousness to severe complications such as withdrawal seizures and delirium tremens. Severity of alcohol withdrawal is directly proportional to the age of the patient,, amount and duration of recent alcohol intake, history of withdrawal seizures/delirium tremens, abnormal liver function, co-existing infection,, or medical problems including pancreatitis or hepatitis., Since alcohol withdrawal symptoms can rapidly worsen, it is important that its severity be assessed quickly and accurately so as to provide adequate and timely intervention to reduce the risk of developing withdrawal seizures and delirium tremens. The severity of withdrawal can be clinically assessed using Clinical Institute Withdrawal Assessment for Alcohol scale-revised (CIWA-Ar); however, blood markers to authenticate the same are still under study.
There is increasing evidence that shows which shows that the severity of withdrawal is related to serum creatine phosphokinase (CPK) levels. The serum CPK activity can differentiate alcohol use into syndrome of dependence (low normal levels), withdrawal (higher), and delirium tremens (highest). In the first few days of alcohol withdrawal, a syndrome of abrupt muscle injury known as “alcoholic rhabdomyolysis” occurs, severity of which ranges from an asymptomatic transient elevation of creatine kinase to frank rhabdomyolysis with myoglobinuria. The pathophysiology includes a common final pathway of cellular injury wherein the noxious factor serves to increase cellular permeability to sodium ions leading to an increase of cytosolic or mitochondrial calcium, activating a variety of proteolytic enzymes injuring cell membrane, and then allowing efflux of cellular components into the circulation. The laboratory marker of this acute alcoholic myopathy is elevation of muscle CPK in serum, which rises in the first 3 days of alcohol withdrawal and then declines to the normal range usually within 7–10 days.
This study was hence conducted to study the relationship between severity of alcohol withdrawal and serum CPK levels in alcohol dependence syndrome cases.
| Methodology|| |
This was a cross-sectional observational study conducted over a period of 01 year. All consecutive cases of alcohol dependence syndrome admitted in alcohol withdrawal state to the psychiatry ward of a tertiary care hospital between 25 and 55 years of age were included in the study. Patients with comorbid medical and psychiatric conditions, namely musculoskeletal trauma, myocardial injury, infections, drug-induced myositis, endocrine, neuropsychiatric, neuromuscular, metabolic, and rheumatologic disorders were excluded from the study.
Ethics committee approval was obtained for the study. Confidentiality was assured and written informed consent was obtained from the subjects. Enrolment of cases was done after applying the inclusion and exclusion criteria to rule out any other cause of raised CPK levels. A total of 143 consecutive cases of alcohol dependence syndrome in alcohol withdrawal state admitted to a tertiary care hospital psychiatry ward were taken up for the study. Twenty-three patients were excluded due to comorbid medical and psychiatric conditions and the remaining 120 were included. Baseline demographic data of cases along with relevant investigations were entered in semi-structured pro forma on admission. The assessment for the severity of alcohol withdrawal was done with CIWA-Ar scale. Blood samples at baseline were taken to measure serum CPK levels. The patients were subsequently managed adequately and an association was made between the serum CPK levels and the severity of withdrawal. The data was analyzed using Chi-square test and Kruskal–Wallis tests.
The revised CIWA-Ar scale is a validated 10-item assessment tool that can be used to quantify the severity of alcohol withdrawal syndrome and to monitor and medicate patients going through withdrawal with high reliability. CIWA-Ar scores of 8 points or fewer correspond to mild withdrawal, scores of 9–15 points correspond to moderate withdrawal, and scores of >15 points correspond to severe withdrawal symptoms and an increased risk of delirium tremens and seizures.
CPK is an indicator of muscle injury and its serum level is directly related to the same. CPK, especially its MB isoenzyme, is a reliable marker of myocardial necrosis and total CPK activity is considered to be a sensitive and excellent biochemical marker for diagnosis of neuromuscular diseases. CK-MB increases in acute myocardial infarction and CK-BB increases in brain damage. In normal serum, total CPK is provided mainly by the skeletal muscle and is almost only of the MM fraction. Blood samples for serum CPK determination were collected in the morning of admission day prior to starting any medication. As per the hospital laboratory, the upper limit for normal CPK in serum for men was 175 U/L.
| Results|| |
Demography and alcohol-related variables
The wmean age of the study group was 37.51 ± 8.12 years. Most of the patients, n = 90 (75%), had started consuming alcohol at an age <25 years with a mean age of onset at 22.26 ± 3.97 years. Majority of the patients, n = 50 (41.66%), had been consuming alcohol for more than 15 years with a mean duration of 15.25 ± 5.86 years. The mean time lapse from the last drink was 2.52 ± 0.35 days. As per the CIWA, 32 (26.66%) patients had mild alcohol withdrawal, 66 (55%) had moderate, and 22 (18.33%) had severe alcohol withdrawal. Serum CPK levels were elevated in 66 (55%) patients [Table 1].
Association between alcohol-related variables and severity of alcohol withdrawal
The association between severity of alcohol withdrawal with mean years of alcohol consumption is shown in [Table 2]. Patients with mild severity of alcohol withdrawal had been consuming alcohol for an average duration of 9.43 years, with moderate severity of withdrawal for 15.06 years, and with severe withdrawal for 24.60 years. The difference was statistically significant (P < 0.0001) which indicated that the severity of alcohol withdrawal was directly related to the number of years of consuming alcohol.
|Table 2: Association of severity of alcohol withdrawal with mean years of alcohol consumption|
Click here to view
The association of severity of alcohol withdrawal with mean CPK scores is shown in [Table 3]. The mean serum CPK level for mild withdrawal as per the CIWA-Ar was 126.93, moderate withdrawal was 303.66, and for severe withdrawal was 780.81. The difference was statistically significant (P < 0.0001) indicating that patients with higher CIWA-Ar scores were likely to have a higher level of serum CPK levels.
|Table 3: Association of severity of alcohol withdrawal with mean creatine phosphokinase levels|
Click here to view
| Discussion|| |
The present study was undertaken to assess the relationship between serum CPK levels and severity of alcohol withdrawal.
Majority (75%) of the patients had started consuming alcohol at an age <25 years, followed by 21.6% between the age group of 25 and 35 years and only 3.3% started drinking at an age more than 35 years (P < 0.0001) [Table 1]. The mean age of onset of alcohol use was 22.26 years. This trend of early onset of alcohol use is in concurrence with a time trend analysis by Nair et al. which observed that the mean age at onset of alcohol use dropped from 24 to 17 years from the pre-1950 birth cohort to the post-1985 birth cohort. In another systematic analysis for the Global Burden of Disease Study (2010), a significant decline in the average age of onset of alcohol consumption was noticed from 28 years during the 1980s to 17 years by 2007. These trends are not very reassuring because the early onset of alcohol use heralds a host of social problems, namely poor social adaptation, aggression and legal issues, exposure to criminal behavior, and gateway to other drugs of abuse.
The mean age of the study population was 37.51 years and 41.66% of patients had been consuming alcohol for more than 15 years with a mean duration of 15.25 ± 5.86 years [Table 1]. The mean duration of drinking in the current study was significantly high (15.25 ± 5.86 vs. 7.6 ± 10.2 years) compared to Ghosh et al. in alcohol-dependent subjects. This could be attributed to comparatively higher mean age in the current study (37.51 years) versus 31.4 ± 10.8 years in the reference study. The severity of alcohol withdrawal was maximum in patients with the highest mean years of alcohol consumption (P < 0.0001) [Table 2]. This was consistent with previous studies on delirium tremens which reported that prolonged drinking and severe dependency predisposes the individual to severe alcohol withdrawal including delirium tremens.
The mean serum CPK level for mild alcohol withdrawal as per the CIWA-Ar was 126.93, moderate withdrawal was 303.66, and for severe withdrawal was 780.81. A statistically significant value of P < 0.0001 was obtained indicating that highest serum CPK levels were found in patients with severe alcohol withdrawal [Table 3]. These observations indicate that CPK has a significant association with severity of alcohol withdrawal and can possibly serve as a candidate biomarker for anticipating the severity of alcohol withdrawal and better preparedness for the management of same. Lafair and Myerson observed a similar trend in which serial serum CPK levels escalated rapidly, reaching a peak in 4–5 days after alcohol cessation followed by a decline to normal without any clinical evidence of acute myopathy. There are case reports of extremely high levels of CPK values (Farrukh et al., 50,043, U/L, and Zahiroddin and Rezaei, 11350 U/L) in delirium tremens patients after ruling out other common causes of rhabdomyolysis., Segal et al. differentiated alcohol-related syndromes based on creatine kinase levels. Subjects during delirium tremens (mean CPK: 1085.58; standard deviation [SD]: 818.77 U/L) were found to have the highest CPK levels followed by subjects during withdrawal (mean: 354.8; SD: 158.76 U/L;) and lowest levels during alcohol dependence (mean: 63.56; SD: 18.15 U/L) but not experiencing a withdrawal. There are other biomarkers such as mean corpuscular volume, gamma-glutamyltransferase, homocysteine, carbohydrate-deficient transferrin, and prolactin which assist in predicting the severity of withdrawal (especially alcohol withdrawal seizure) and to individualize intensive therapy for effective management. However, none of these above biomarkers have optimal sensitivity and specificity alone. The findings of the current study thus indicates that CPK assessment during alcohol withdrawal has the potential of increasing the predictability of withdrawal severity when used alone or in conjunction with the abovementioned alcohol biomarkers.
The strength of study is that this is the first study to the best of our knowledge which has associated the severity of alcohol withdrawal using validated scales with raised serum CPK levels after stringent inclusion and exclusion criteria eliminating other possible causes of raised CPK levels.
The limitations were that it was a cross-sectional study with a relatively small sample size consisting only of males in a tertiary care hospital; limiting its generalizability to community. Second, only a single biomarker was studied without prewithdrawal sample collections or follow-ups which would have provided us valuable knowledge about the longitudinal variation in serum CPK. A longitudinal study with larger sample size and community follow-up is recommended for further confirming the findings.
| Conclusion|| |
These observations indicate that serum CPK levels have a statistically significant association with severity of alcohol withdrawal and can possibly serve as a candidate biomarker for anticipating the severity of alcohol withdrawal and better preparedness for the management of same.
The authors would like to thank all the subjects who consented to participate in this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Alderazi Y, Brett F. Alcohol and the nervous system. Curr Diagnos Pathol 2007;13:203-9.
Murthy P, Manjunatha N, Subodh BN, Chand PK, Benegal V. Substance use and addiction research in India. Indian J Psychiatry 2010;52:S189-99.
Shield KD, Parry C, Rehm J. Focus on: Chronic diseases and conditions related to alcohol use. Alcohol 2013;85:2.
Bayard M, Mcintyre J, Hill KR, Woodside J. Alcohol withdrawal syndrome. Am Fam Physician 2004;69:1443-50.
van Munster BC, Korevaar JC, de Rooij SE, Levi M, Zwinderman AH. Genetic polymorphisms related to delirium tremens: A systematic review. Alcohol Clin Exp Res 2007;31:177-84.
McKeon A, Frye MA, Delanty N. The alcohol withdrawal syndrome. J Neurol Neurosurg Psychiatry 2008;79:854-62.
Lee JH, Jang MK, Lee JY, Kim SM, Kim KH, Park JY, et al
. Clinical predictors for delirium tremens in alcohol dependence. J Gastroenterol Hepatol 2005;20:1833-7.
Wright T, Myrick H, Henderson S, Peters H, Malcolm R. Risk factors for delirium tremens: A retrospective chart review. Am J Addict 2006;15:213-9.
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: The revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989;84:1353-7.
Segal M, Avital A, Rusakov A, Sandbank S, Weizman A. Serum creatine kinase activity differentiates alcohol syndromes of dependence, withdrawal and delirium tremens. Eur Neuropsychopharmacol 2009;19:92-6.
Biscaldi G, Guarnone F, Fonte R, Finozzi E, Grossi R, Taglione L. Acute alcoholic myopathy. Recenti Prog Med 1994;85:537-9.
Ford CS, Caldwell SH, Kilgo GR. Acute alcoholic myopathy. Am Fam Physician 1984;29:249-52.
Hilton-Jones D. Myositis mimics: How to recognize them. Curr Opin Rheumatol 2014;26:663-70.
Reoux JP, Miller K. Routine hospital alcohol detoxification practice compared to symptom triggered management with an Objective Withdrawal Scale (CIWA-Ar). Am J Addict 2000;9:135-44.
Lohr RH. Treatment of alcohol withdrawal in hospitalized patients. Mayo Clin Proc 1995;70:777-82.
Galassi G, Rowland LP, Hays AP, Hopkins LC, DiMauro S. High serum levels of creatine kinase: Asymptomatic prelude to distal myopathy. Muscle Nerve 1987;10:346-50.
Nair UR, Vidhukumar K, Prabhakaran A. Age at onset of alcohol use and alcohol use disorder: Time-trend study in patients seeking de-addiction services in Kerala. Indian J Psychol Med 2016;38:315-9.
] [Full text]
Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al
. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: A systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2224-60.
Johnson PR, Banu S, Ashok MV. Severity of alcoholism in Indian males: Correlation with age of onset and family history of alcoholism. Indian J Psychiatry 2010;52:243-9.
Ghosh S, Samanta A, Mukherjee S. Patterns of alcohol consumption among male adults at a slum in Kolkata, India. J Health Popul Nutr 2012;30:73-81.
Schuckit MA, Tipp JE, Reich T, Hesselbrock VM, Bucholz KK. The histories of withdrawal convulsions and delirium tremens in 1648 alcohol dependent subjects. Addiction 1995;90:1335-47.
Lafair JS, Myerson RM. Alcoholic myopathy. With special reference to the significance of creatine phosphokinase. Arch Intern Med 1968;122:417-22.
Farrukh A, Pau D, Venkata C. Severe Delirium Tremens: An Unusual Cause of Rhabdomyolysis with Extreme Serum Creatine Kinase Elevation. InA46. Critical Care Case Reports: Acid Base, Electrolytes, Endocrine, Metabolic And Renal 2019 May (pp. A1738-A1738). American Thoracic Society.
Zahiroddin AR, Rezaei Z. Alcohol induced rhabdomyolysis. Kidney 2016;1:7.
Rinck D, Frieling H, Freitag A, Hillemacher T, Bayerlein K, Kornhuber J, et al
. Combinations of carbohydrate-deficient transferrin, mean corpuscular erythrocyte volume, gamma-glutamyltransferase, homocysteine and folate increase the significance of biological markers in alcohol dependent patients. Drug Alcohol Depend 2007;89:60-5.
[Table 1], [Table 2], [Table 3]