|Year : 2023 | Volume
| Issue : 1 | Page : 17-20
A clinical audit of diuretic use in a cohort of patients with decompensated chronic liver disease in South India
Uday Sanglodkar1, Mayank Jain2, Jayanthi Venkataraman3
1 Department of Hepatology, Dr. Rela Institute and Medical Centre, Chennai, Tamil Nadu, India
2 Arihant Hospital and Research Centre, Indore, Madhya Pradesh, India
3 Department of Hepatology, Sri Ramachandra Medical College, Chennai, Tamil Nadu, India
|Date of Submission||19-Oct-2022|
|Date of Decision||08-Nov-2022|
|Date of Acceptance||09-Nov-2022|
|Date of Web Publication||28-Dec-2022|
297, Indrapuri, Indore, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Background and Aim: Diuretic doses for the optimal management of ascites may be influenced by the patient profile and conditions. We undertook this study to map the usage of common diuretics, alone or in combination, for the management of patients with decompensated cirrhosis and to determine the prevalence of adverse effects with the administered regimens and factors that predict the need for paracentesis while on diuretics. Methods: This prospective study was done in an outpatient clinic among patients with known liver cirrhosis, irrespective of etiology, belonging to Child-Pugh Class B or C, with mild to moderate ascites and no dyselectrolemia on diuretics. The primary outcome of the study was the need for paracentesis. The type and dose of diuretic at this instance were noted. Results: A total of 200 patients (168 male), predominantly from southern Indian states, formed the study group. The median model for endstage liver disease score was 18 and 70% of cases required paracentesis within 3 months. The single diuretic agent was used in 18% of cases while combination of two diuretics was used in 82%. Spironolactone was the most common single agent used (26, 72.2%). The combination of furosemide and spironolactone was the most common diuretic combination used (89.6%, 147 cases). One hundred and thirty patients (65%) reported the adverse effects to diuretics. Renal dysfunction and electrolyte disturbances were the most common adverse effects. Adverse effects to diuretic use and frequency of large volume paracentesis were significantly more common in patients taking furosemide 40 mg and spironolactone 100 mg per day. Conclusions: Indian patients with decompensated chronic liver disease do not appear to tolerate the high doses of diuretics and 65% of them develop diuretic-related adverse effects. There is a need to formulate the guidelines for the optimal management of ascites in decompensated chronic liver disease in the Indian setting.
Keywords: Ascites, cirrhosis, diuretics, drug treatment
|How to cite this article:|
Sanglodkar U, Jain M, Venkataraman J. A clinical audit of diuretic use in a cohort of patients with decompensated chronic liver disease in South India. Gastroenterol Hepatol Endosc Pract 2023;3:17-20
|How to cite this URL:|
Sanglodkar U, Jain M, Venkataraman J. A clinical audit of diuretic use in a cohort of patients with decompensated chronic liver disease in South India. Gastroenterol Hepatol Endosc Pract [serial online] 2023 [cited 2023 Mar 20];3:17-20. Available from: http://www.ghepjournal.com/text.asp?2023/3/1/17/365722
| Introduction|| |
Ascites is a common complication of cirrhosis. About 50% of patients with compensated cirrhosis develop ascites within 5 years. With the onset of ascites, the survival probability decreases by 50% within the next 2 years. Diuretics remains the mainstay for the management of mild-to-moderate ascites. Common diuretics in day-to-day practice include spironolactone, furosemide or torsemide either as a single drug or as combinations. Vaptans and amiloride are used sparingly in select situations.
It has been a common observation in our day-to-day practice that the majority of our patients with decompensated liver disease have never reached the maximum dose recommended by either EASL or American Association for Study of Liver Disease (AASLD) guidelines., Majority are intolerant to this high dosing or suffer from adverse effects. Japan and China have recently tailored the diuretic dose schedule to their respective population and have redefined refractory ascites for their select population, which is distinct from the West.,,,
We undertook this prospective observational study amongst patients with decompensated chronic liver disease, to determine the practice of diuretic prescription (either single or in combination) by the consultants in a tertiary level liver unit in Southern India and document the adverse effects related to diuretic dose.
| Methods|| |
This study was done at Gleneagles Global Health City, Chennai, India between January 2018 and June 2018. Patients were recruited for the initial 3 months and then followed up for the next 3 months [Figure 1].
Selection of cases
Patients of Indian origin with decompensated liver disease, (Child-Turcotte-Pugh [CTP] B or C) with a diuretic prescription instituted by our consultants and followed up for at least a month in the outpatient clinic were included. Budd Chiari syndrome, ascites due to heart failure or constrictive pericarditis, nephrogenic ascites, malignant ascites (primary or secondary), spontaneous bacterial peritonitis (SBP), and tuberculous peritonitis were excluded.
Patient information included etiology of cirrhosis, comorbidity, model for endstage liver disease (MELD), and CTP score. The diagnosis of cirrhosis was confirmed by ultrasound or computed tomography, documentation of esophageal varices at endoscopy or and venous collaterals at imaging.
On the day of registration, details of diuretic use including the generic name of the drug, dose and timing of medication (single dose in the morning or split dose in the morning and afternoon) were collected. Response to diuretic was assessed by the measure of urine output (by direct interview or telephonic conversation) on the daily basis for the 1st week and thereafter once in 3 days for the next week. An output of 1000 to 1500 mL per day was considered adequate, >1.5 L as excessive and <1000 mL as inadequate. Reduction in weight as a response to diuretic was not considered due to practical issues like out station patients. Note was made when dose or type of diuretic was changed or patients had experienced adverse effects or developed refractory ascites. Refractory ascites was defined as when patients could not tolerate the next escalating dose of diuretic, had tense ascites, reduced urine output of <500 ml per day and needed large volume paracentesis (LVP). As per the unit protocol, need-based salt restriction with diet recommendations was instituted to all patients at the time of first registration to the liver clinic.
The end point of the study was either adverse effects in the form of renal failure or dyselectrolemia or the onset of refractory ascites requiring LVP within 3 months of follow-up. The dose and type of diuretic at the primary and secondary and points were noted.
Ethics committee of the Institution approved the study.
Since there was no similar study available from India, a sample size to 150–200 was considered adequate. Descriptive analysis was carried out by the median and range for the quantitative variables and frequency and proportion for the categorical variables. Chi-square test, Mann–Whitney U-test, Fischer's exact test, and odds ratio were calculated. P < 0.05 was considered statistically significant.
| Results|| |
Out of 226 registered cases with cirrhosis-related ascites, 26 were excluded (SBP) as per the study criteria. Majority of the recruited patients (148; 79%) were from the southern states of the Indian subcontinent [Table 1]; 168 (84%) were men. The two common causes of cirrhosis were nonalcoholic steatohepatitis (74; 37%) and alcohol (70; 35%). There were equal number of patients belonging to CTP B or C. The median MELD score was 18. One hundred and forty patients (70%) with refractory ascites required LVP within 3 months.
Diuretics: Choice and dose
Thirty-six (18%) received a single diuretic while 164 (82%) received a combination of diuretics [Table 2]. The most common single diuretic prescribed was spironolactone (26; 72.2%) and combination diuretic was furosemide + spironolactone (89.6%, 147 cases). The latter combination was prescribed as either 20 + 50 or 40 + 100 mg per day in 178 (89%) cases and given at 7 am in 22 and a second dose at 3 pm in 22 (11%). Majority of patients receiving combination of two diuretics were given this as a fixed dose combination pill (180, 90%). Urine output was maximal between 5 and 8 PM in those taking a single morning dose and between 9 PM and midnight with dual dose. Overall, urine output was excessive in 20 (12.2%), adequate in 124 (75.5%) and inadequate in 20 (12.2%) with combination diuretics. Adverse effects to combination of diuretics [Figure 1].
Overall, 130 patients reported adverse effects, the two common ones being renal dysfunction and electrolyte disturbances. Between the two commonly used combination, [Table 3]a and [Table 3]b, the adverse effects and frequency of LVP were significant among those prescribed furosemide 40 mg and spironolactone 100 mg per day. The odds of developing diuretic induced complications (2.96; 95% confidence interval [CI] 1.2–7.39) (P < 0.02) and need for LVP (8.14; 95% CI 3.13–21.15) (P < 0.00001) was also significantly high in this subgroup. Majority of these patients belonged to CTP class C with a significant higher MELD score [Table 4].
|Table 4: Comparison of patient characteristics with the two commonly used diuretic combination|
Click here to view
| Discussion|| |
The present study highlights that in our institutional practice, the most common single diuretic prescribed for the control of ascites is spironolactone, while the commonly used combination is furosemide with spironolactone. Even at lower doses, 130 (65%) patients developed diuretic-related adverse effects. These are more often seen with furosemide 40 mg and spironolactone 100 mg per day combination.
Comparing our preliminary observations with the AASLD recommendations, we found that even an initial combination dose of 40 mg furosemide and 100 mg spironolactone resulted in significant adverse effects. Ten patients (5%) in our study received furosemide or torsemide alone, which is not recommended as per the AASLD guidelines. Few other deviations from AASLD that were noticeable were twice a day dosing in 11%, the recommendation being the use of a single morning dose and failure to maintain the 2:5 ratio (20%) for furosemide and spironolactone. These observations underscore the fact that recommendations regarding diuretic use are not followed and that there is an urgent need to address several of the lacunae while prescribing diuretics.
We recommend that there is a need to set the guidelines for diuretic use in the Indian setting as none of our patients tolerated the high doses recommended in the western literature and develop side effects to diuretics even at low doses. This may be related to the low muscle mass and poor nutritional status common among our patients. Moreover, dietary factors and the hot and humid conditions may contribute to these differences. Another point to highlight is the low compliance to western recommendations in management. This may be attributable to personal experience and preferences of the treating doctors, patient factors, and drug side effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Runyon BA, Antillon MR. Ascitic fluid pH and lactate: Insensitive and nonspecific tests in detecting ascitic fluid infection. Hepatology 1991;13:929-35.
European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010;53:397-417.
Ohki T, Sato K, Yamada T, Yamagami M, Ito D, Kawanishi K, et al.
Efficacy of tolvaptan in patients with refractory ascites in a clinical setting. World J Hepatol 2015;7:1685-93.
Tahara T, Mori K, Mochizuki M, Ishiyama R, Noda M, Hoshi H, et al.
Tolvaptan is effective in treating patients with refractory ascites due to cirrhosis. Biomed Rep 2017;7:558-62.
Bossen L, Krag A, Vilstrup H, Watson H, Jepsen P. Nonselective β-blockers do not affect mortality in cirrhosis patients with ascites: Post hoc
analysis of three randomized controlled trials with 1198 patients. Hepatology 2016;63:1968-76.
Zhang X, Wang SZ, Zheng JF, Zhao WM, Li P, Fan CL, et al.
Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients. World J Gastroenterol 2014;20:11400-5.
[Table 1], [Table 2], [Table 3], [Table 4]