|Year : 2019 | Volume
| Issue : 5 | Page : 1075-1083
|Intensive monitoring of adverse drug reactions in nephrology unit of tertiary care teaching hospital
Shoukath Ali Kareem1, Sathvik Belagodu Sridhar2, Manjunath S Shetty3
1 Department of Pharmacy Practice, JSS College of Pharmacy, Mysore, Karnataka, India
2 Department of Clinical Pharmacy and Pharmacology, RAK College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al-Khaimah, United Arab Emirates
3 Department of Nephrology, JSS Medical College Hospital, Mysore, Karnataka, India
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|Date of Submission||28-May-2018|
|Date of Decision||03-Nov-2018|
|Date of Acceptance||04-Nov-2018|
|Date of Web Publication||4-Nov-2019|
| Abstract|| |
Adverse drug reactions (ADRs) are one of the common causes of morbidity and mortality. Renal insufficiency is considered as one of the risk factors for the development of ADR. The study determined the occurrence of ADRs in patients with renal failure and their incidence of hospital admission. The study also evaluated the nature and severity of ADRs. This was a prospective study conducted in the nephrology unit at a tertiary care teaching hospital for a period of nine months. Patients receiving regular hemodialysis and those either referred or admitted to the nephrology ward were included. ADRs were intensively monitored throughout the study. The causality of suspected ADRs was assessed with the WHO probability scale, Naranjo algorithm, and Karch and Lasagna’s scale. The predictability and preventability of ADRs were also determined. A total of 45 ADRs were identified in 369 patients; incidence was 12.19%. Nine ADRs (20%) needed hospitalization. A total of 27 (60%) and 17 (37.8%) ADRs were found to be probable and possible, respectively when assessed by the WHO probability scale. On the contrary, 33 (73.3%) and 26 (57.8%) ADRs were possible in causality when assessed by Karch and Lasagna’s scale and Naranjo scale, respectively. Most of the ADRs [26 (57.8%)] were predictable in nature. A wide range of ADRs was noticed in patients with renal impairment, and our study has systematically assessed the nature and severity of ADRs.
|How to cite this article:|
Kareem SA, Sridhar SB, Shetty MS. Intensive monitoring of adverse drug reactions in nephrology unit of tertiary care teaching hospital. Saudi J Kidney Dis Transpl 2019;30:1075-83
|How to cite this URL:|
Kareem SA, Sridhar SB, Shetty MS. Intensive monitoring of adverse drug reactions in nephrology unit of tertiary care teaching hospital. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2020 Sep 19];30:1075-83. Available from: http://www.sjkdt.org/text.asp?2019/30/5/1075/270263
| Introduction|| |
Globally, adverse drug reactions (ADRs) are the most important problem representing one of the leading causes of mortality and morbidity in health-care facilities. Studies have demonstrated the incidence of ADRs in hospitalized patients., About 0.2%–21.7% of hospital admissions occur due to ADRs. Majority of the drugs and their metabolites are eliminated by the kidney. However, accumulation of the drug or its metabolite can occur in renal impaired patients, resulting in severe and life-threatening adverse events, which can be provoked by comorbid conditions. In general, renal failure patients on hemodialysis (HD) have multiple comorbidities either as a result of, or as a cause of end-stage renal disease (ESRD). Hence, these patients are often treated with 10–12 medications. Simultaneous administration of numerous drugs may contribute to drug-related problems.
Renal insufficiency is a well-recognized risk factor for the development of ADRs. It is noteworthy that the overall incidence of ADRs is 3–10 times higher in elderly patients with kidney disease when compared to healthy individuals. Thus, any alteration in the renal function has uniformly predictable influence on the possibility of causing ADRs. Another retrospective study demonstrated significant impact of renal impairment on various characteristics of ADRs. Although adverse drug events are common in renal compromised patients, Hug et al reported that most of these adverse drug events can be prevented by validating the renal dose.
Evaluation of the incidence and prevalence of ADRs is important to determine the outcomes and impact of their effect on patients. It has been reported that awareness of ADRs can prevent its occurrence or allows for its early identification and treatment, thereby reducing morbidity and mortality due to ADRs. Clinical pharmacists can play a pivotal role in ADR monitoring and reporting, as the majority of serious ADRs occur in a hospital setting and contribute to a significant proportion of hospital admissions. Studies have also reported other mitigation strategies such as computerized physician order entry system in potentially preventing ADRs. There are a limited data regarding prospective studies carried out by the clinical pharmacist in determining the incidence and occurrence of ADRs in patients with renal impairment in developing countries. Hence, the primary objective of this study was to determine the occurrence of ADRs in renal impaired patients and to identify the incidence of ADRs needing hospital admission due to renal failure. The study also aimed to evaluate the nature of ADRs with respect to possibility, preventability, and predictability.
| Subjects and Methods|| |
This was a prospective study conducted in the nephrology unit of an Indian tertiary care teaching hospital over a nine-month period. This study was approved by the Institutional Research and the Ethics Committee of the hospital. The latter is 1000-bed hospital with several medical specialties. Nephrology unit is one among those specialties comprising 50 beds including inpatient and HD unit.
Inclusion criteria and data collection
Patients admitted to the nephrology unit, including male and female nephrology wards, and HD unit were enrolled in the study. In addition, patients who were referred to the nephrology unit from different specializations (such as emergency, intensive care unit, surgical units) were included. Patients who were treated in the outpatient department of the nephrology unit were excluded. In this study, the authors accompanied the team of nephrologists on medical ward rounds for six days in a week. Each ward round lasted for an average of 2.5–3 h/day.
The study data were collected from the patients’ case notes, treatment chart, laboratory investigation reports, patients’ diaries and by conducting interviews of the patient and/or caretaker. The collected data were documented in the documentation form that was designed for the study. Investigators intensively monitored the patients for ADRs from the 1st day of their admission at the study site till the day of their discharge. The research team followed up all the patients having abnormal renal functions (glomerular filtration rate <60 mL/min/ 1.73 m2 and serum creatinine >1.4 mg/d). The estimated creatinine clearance of all the patients admitted under nephrology unit were determined by using the Cockroft–Gault formula by the research investigators during prerounds, ward rounds, or postrounds on a regular basis (based on the availability of laboratory results). Only patients having abnormal renal function were included in the study.
Evaluation of the data
The attending clinical pharmacist determined whether the patient had an adverse drug event, and the strength of the relationship between the adverse drug event and the suspected drug was assessed. Subsequently, this was brought to the notice of the concerned treating nephrologist. Similarly, ADRs reported by nephrologists were evaluated by the first and second authors. The causality was assessed using a WHO probability scale, Naranjo algorithm and Karch and Lasagna’s scale. In addition, the severity (Modified Shumock and Thornton) and predictability and preventability of suspected ADRs were also assessed and documented.
| Results|| |
Over a period of nine months, 378 patients were enrolled in the study. However, only 369 patients (320 inpatients and 49 regular dialysis patients) were followed up, and the remaining nine patients were lost to follow-up. The majority of study patients were in the age-group of 51–55 years. About 128 patients had two comorbidities, and average number of medications prescribed was 7.12 ± 3.26 per patient. The demographic, disease, and treatment-related characteristics are summarized in [Table 1].
|Table 1: Demographic, disease, and treatment-related characteristics of the study patients.|
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A total of 45 ADRs were recognized with the incidence being 12.19% (incidence of ADRs = 45/369 × 100 = 12.19%). Incidence was higher in male patients (n = 26, 57.8%) when compared to female patients (n = 19, 42.2%). Of 45 ADRs, 36 (80%) ADRs occurred in patients during hospital stay and nine (20%) ADRs were the reason for hospital admission. ADRs were more common in patients aged ≥61 years (n = 12, 26.7%) followed by patients with age 29–39 years (n = 10, 22.3%), 51–60 years (n = 9, 20%) and seven ADRs each (15.5%), in the age-group of 18–28 and 40–50 years.
Antibiotics (n = 8, 17.7%) were the most frequent class of medications that were involved in the development of ADRs followed by opioid analgesics (n = 7, 15.5%) [Table 2]. Vomiting was the most commonly suspected ADR (n = 6, 13.3%) followed by diarrhea (n = 4, 8.8%), rash (n = 4, 8.8%), abdominal pain (n = 4, 8.8%), and dizziness (n = 4, 8.8%). Tramadol (n = 7, 15.5%) was found causing ADRs in more number of patients followed by erythropoietin (n = 2, 4.4%), prazosin (n = 2, 4.4%), prednisolone (n = 2, 4.4%), rabeprazole (n = 2, 4.4%), and rifampicin (n =2, 4.4%) [Table 3].
Out of nine ADRs responsible for hospital admission, anti-tubercular drug (rifampicin) was the most common drug responsible for hospitalization (n = 2, 22.2%) of the patients. Only one ADR was serious, whereas the remaining eight ADRs were managed with appropriate medical treatment [Table 4].
|Table 4: Drug-induced adverse drug reactions responsible for hospitalization.|
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The causality of suspected ADRs was found to be probable, possible, and un-assessable for 27 (60%), 17 (37.7%), and one ADRs (2.2%), respectively, when evaluated by the World Health Organization (WHO) probability scale. According to Naranjo’s algorithm, 26 ADRs (57.7%) were classified as possible followed by 19 ADRs as probable (42.2%). On the contrary, when Karch and Lasagna’s scale was applied to determine the causality of the ADRs, the nature of ADRs for the majority of the ADRs were possible (n = 33, 73.3%) followed by probable (n = 12, 26.6%).
About 26 ADRs (57.7%) and 19 ADRs (42.2%) were found to be predictable and unpredictable in nature, respectively. About 30 ADRs (66.6%) were definitely preventable and 13 ADRs (28.8%) were probably preventable. Of 45 ADRs, 18 (40%) and 19 (42.2%) ADRs were found to be mild and moderate in severity, respectively [Table 5].
| Discussion|| |
The WHO defines ADR as “a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function.” However, Edwards et al defined ADR as “an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product.”
ADRs are a common clinical problem as they imitate numerous diseases and cause significant morbidity and mortality. It is eminent that adverse drug events are more common in hospitalized chronic kidney patients. The prevalence of ADRs is 3–10 times higher in elderly patients with renal disease when compared to those with normal kidneys. This could be due to the accumulation of most of the drugs and their metabolites (that are cleared by kidneys) in patients with compromised renal function. Furthermore, altered pharmacokinetics and polypharmacy increases the risk for the development of ADRs in kidney disease patients., In addition, change in drug distribution, protein-binding, metabolic abnormalities or decrease in the elimination rate of the drug or its toxic metabolite may lead to ADRs in renal insufficiency patients. An Indian study has demonstrated that renal impairment has a significant impact on various characteristics of ADRs.
In general, HD patients have multiple comorbidities and require 10–12 medications either as a result of or as a cause of ESRD. In our study, most of the patients had two comorbidities and were receiving 7.12 ± 3.26 drugs on an average which was similar to a previous study. The overall incidence of ADR in our study population was found to be 12.9% which was less compared to a previously published study (17%). The lower incidence of ADRs in our study could be due to variation in the study design and number of study patients.
Unlike the previous study, which retrospectively included 1464 case records of renal impaired patients, the present study was a prospective study with very few numbers of patients (n = 369). In addition, optimal prescribing of the drugs by the nephrologists and intensive monitoring of ADRs could be the other reasons for the decreased incidence of ADRs in this study.
Tran et al have demonstrated that female gender is a risk factor for the occurrence of ADRs. In the present study, we noticed that male patients experienced more ADRs when compared to female patients. This finding is in agreement with earlier reports that have documented an increased occurrence of ADRs in male patients with renal impairment. However, in the present study, it is not possible to rule out the fact that the increased number of ADRs in males could be due to a larger number of male patients admitted under nephrology care when compared to female patients.
The older people are at greater risk of developing ADRs owing to age-related changes in the pharmacokinetics and pharmacodynamic parameters of the drugs that are used to treat multiple comorbidities. Previous studies have reported that ADRs are commonly observed in elderly patients when compared to children or adults., These findings are in agreement with the observation in our study, wherein most of the ADRs were observed in patients aged >61 years. Antibiotics followed by opioid analgesics were the most common drug classes responsible for the development of ADRs. Hug et al in their retrospective cohort study, also demonstrated antibiotics as the most frequent class of drugs responsible for ADRs in renal failure patients.
Of 45 ADRs, 36 (80%) occurred in patients during their hospital stay. This finding was found to be contradicting with the pre-vious studies, wherein the prevalence of ADRs was 5.3%-6.7% in hospitalized patients., The increased number of ADRs in our patients during the hospital stay could be attributed to several factors. One such factor could be the presence of more than two comorbidities in HD patients, which often requires several drugs that subsequently, increases the risk of ADRs. Further, to the best of our knowledge, data to support the increased incidence of ADRs in patients with renal impairment (as observed in this study) is lacking.
Various classes of drugs, especially antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs) can adversely affect the kidney resulting in tubulointerstitial, glomerular, or vascular disease. During the study, we reported nine ADRs (20%) which were responsible for hospital admission, antitubercular drugs (4.4%) being the most common class of drugs responsible for this. It has been reported that rifampicin can rarely cause interstitial nephritis.
Similarly, NSAIDs can disrupt renal hemodynamics and lead to acute renal failure, especially in elderly patients and also they are associated with increased risk of hospitalization. A study conducted by Corsonello et al reported concealed renal function in the elderly as an independent risk factor for ADRs to hydrosoluble drugs.
In this study, two patients had been hospitalized due to rifampicin-induced interstitial nephritis and one patient for NSAID-induced interstitial nephritis, which were confirmed by renal biopsy. All the patients who had been hospitalized due to ADRs had recovered after appropriate treatment provided by the nephrologists except for one patient who developed chronic renal failure due to methotrexate.
The number of ADRs in our study when assessed by the WHO causality scale was found to be less compared to the study conducted by Joshua et al (290 vs. 27). This disparity in the findings could be attributed to the number of study patients. A previous prospective, descriptive, observational study demonstrated 58.5% and 7.1% of the ADRs as moderate and severe in nature, respectively. In the present study, only 42.2% of the ADRs were moderate in nature. In one instance, one ADR was found to be severe (level 5), in which furosemide had induced hypokalemia and patient had to stay in the hospital until serum potassium levels returned to normal, thus increasing the length of hospital stay.
| Conclusion|| |
ADRs are becoming one of the important concerns for health-care providers, especially in renal compromised patients. Our study shows that the incidence of ADRs continues to exist in this population. The causality, preventability, and predictability are important parameters that need to be considered while intensively monitoring the ADRs in renal compromised patients.
| Acknowledgments|| |
The authors would like to thank all the administrators of the study site and JSS College of Pharmacy, Mysore, Karnataka, India for their support during the study period. We also extend our thanks to all the staff of nephrology department, of the study site for their help and co-operation during the study period.
Conflict of interest: None declared.
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Sathvik Belagodu Sridhar
Department of Clinical Pharmacy and Pharmacology, RAK College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al-Khaimah
United Arab Emirates
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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