An Intensive Monitoring of Adverse Drug Reactions in Indoor Patients of Paediatric Department at Tertiary Care Teaching Hospital in Gujarat, India

Adverse Drug Reactions (ADRs) are a major source of concern in paediatric population as they differ from adults in pharmacokinetic and pharmacodynamics responses. ADRs reported in adults do not predict those in children. Thus, this study aimed to intensively monitor ADRs occurred in inpatients of paediatric department of tertiary care teaching hospital to assess the same in terms of incidence, causality, severity and preventability. A prospective observational single centre study was done in the paediatric department of SSG hospital, Vadodara over duration of 8 months. The ADRs were actively monitored and collected reports were analysed for ADR pattern, demographic profile, causality, severity, and preventability. A total of 66 ADRs were documented during the period of 8 months. Among these 53.03% ADRs occurred below the age of 1 year, 89.13% ADRs occurred due to antibiotics, 56.06% ADRs are of Diarrhoea and vomiting and 80.43% ADRs developed after receiving drug intravenously. As per WHO-UMC criteria, 46.96 % ADRs were of probable while 51.51% ADRs were of possible causality while as per Naranjo scale 60.61% ADRs were of probable and 39.39% ADRs were of possible category. As per severity scale 69.70% reactions were mild and 30.30 % reactions were moderate. Probably preventable ADRs were about 57.58%. ADRs occurred more among infants and antibiotics were more commonly implicated. Most of the reactions were of mild severity and were probably preventable. Certain Precautionary measures can lead to significant prevention of ADRs in paediatric patients.


Introduction
Drugs, no matter how safe and efficacious, are always coupled with inescapable risk of adverse reactions. Adverse Drug Reactions (ADRs) have been implicated as a leading cause of considerable morbidity & mortality. 1 ADRs are a major clinical problem, accounting for increased resources and also have an economic impact. 2 Incidence of ADRs varies with studies ranging from as low as 0.15% to high as 30% globally. 3,4 It has been suggested that patients who developed adverse effects during hospitalization, were hospitalised for an average of 1.2-3.8 days longer than patients who did not, with a substantial increase of the healthcare costs. 5 Up to 57% of the community acquired ADRs are not being recognized by the attending physician upon hospital admission, leading to inappropriate management of the adverse event and exposure of the patient to additional hazards doi: 10.15416/pcpr.v4i3. 30769 of the drug and prolonged hospitalization. 6 The safety of drugs used in patients of an adult age group cannot be extrapolated to a paediatric age group. The pharmacokinetics and pharmacodynamics of many commonly used drugs vary significantly between these two age groups of patients 7 further, ADRs in children can have a relatively more severe effect when compared to adults. Thus, the ADRs can lead to significant morbidity among children. 8 It has been observed that ADRs in children not only result in hospital admissions or prolonged hospitalization but also may lead to permanent disability or even death. 9 They constitute a reported incidence of 9.5%, including 2.1% of hospital admissions, with 39.3% of them being life-threatening. 10 The safety profile of a drug thus marketed with its testing done on adults can vary significantly when used in children. 11 This aspect of drug therapy is often difficult to predict for newer drugs. An active drug surveillance system is needed to capture risk information in children. 12 Spontaneous reporting plays a major role in the identification of safety signals once the medicine is marketed and it may also provide important information on at-risk groups, risk factors (to a limited degree), and clinical features of known and serious ADRs. Also we cannot detect the incidence and the "spontaneous" part in prescribers is always lacking. 13 As a result, spontaneous reporting captures only a small fraction of the adverse events that actually take place (underreporting). 14 There are strong biases in reporting. 15 The present study was carried out to study the incidence and the pattern of ADRs taking place in paediatric units including wards, PICU and NICU of a tertiary care teaching hospital named Sir Sayajirao General Hospital, Vadodara, Gujarat, India, a tertiary care teaching hospital over a period of eight months from January 2018 to August 2018. This intensive monitoring of ADRs was planned with the intention that the results obtained will be able to shed light on their extensiveness and pattern of occurrence in the tertiary care hospital.

Methods
This study involved intensive monitoring of ADRs in paediatric units including wards, Paediatric Intensive Care Unit (PICU) and Neonatal Intensive Care Unit (NICU) of a tertiary care teaching hospital named Sir Sayajirao General Hospital Vadodara, Gujarat, India. The data were collected for 8 months from January 2018 to August 2018. For Intensive monitoring of ADRs patient were observed and studied for any type of ADRs and various data about demographic details, past history, findings on general and systemic examination, laboratory investigation reports, diagnosis, and treatment were collected from prescription records.
The collected data were recorded in a predefined Case Record Form (CRF) and analysed using Microsoft Excel. This study was approved by Institution Ethics Committee for Human Research (IECHR), Medical College Baroda. Written informed consent was taken from parents before collection of data.

Inclusion Criteria
1. All patients of either sex or ≤ 12 years of age group.

Patients transferred from PICU and NICU
to Paediatric wards. 3. Patients referred to higher centre, or discharged against medical advice but in whom the outcome of ADR was known were included in the study.
Exclusion Criteria 1. >12 years of age groups patients 2. Patients referred to higher centre, or discharged against medical advice and in whom outcome of ADR was not known 3. Patients who developed an ADR during transfusion of blood or blood products and vaccines 4. Patients with intentional or accidental poisoning, drug abuse and patients with non-compliance

Statistical Analysis
Results were expressed in absolute number and percentages. Analysis of results were done after data were entered in Microsoft excel 2016.  A causality assessment carried out as per WHO-UMC criteria revealed that 46.96% (31/66) ADRs were probable while 51.51% (34/66) were possible (Figure 4). In Naranjo scale most of the causality assessments     18 showed 60%. Antimicrobial drugs are the most frequently prescribed drugs in the hospital and to a great extent, the large amount of their use may be considered injudicious. Therefore, these agents are quite likely to be the most common offending group.

Results and Discussion
The causality assessment of the ADRs was carried out on the basis of two popular methods used for this purpose, namely WHO-UMC criteria 19 and Naranjo scale. 20  The present study has generated very useful data for our hospital as well as other tertiary care teaching hospitals, particularly in the Indian context. The data generated in this study can be a guide which can help to prevent majority of undesirable drug effects observed by undertaking precautionary right steps in the right direction when treating with the same drugs in future.
Patients suffering from tuberculosis and HIV/ AIDS were very few in my study. All the same TB and HIV as well as their co-infections are a burning issue globally and require treatment using multiple drug regimens. Thus, these groups should be studied separately in terms of their ADRs profile and causality keeping in mind the increased chances of drug-drug interaction.

Conclusion
Our study has some limitations such as we studied only paediatric unit so same level of intensive monitoring can be done in other departments also. Other limitation is that patients were not followed after discharge so late in some patients late ADRs were remain undetected. Though the duration of the study was adequate, but not enough to be able to cover all the seasons in a year. So in our study we come to conclusion that ADRs occurred more among infants and antibiotics were more commonly implicated. Most of the reactions were of mild severity and were probably preventable. Certain Precautionary measures can lead to significant prevention of ADRs in paediatric patients.