Identification and resolution of drug-related problems in the cardiovascular surgery unit of a tertiary hospital in China: a retrospective study

Abstract

Objective

The prevalence and characteristics of drug-related problems (DRPs) in the cardiovascular surgery unit have not been adequately explored, leaving a gap in our understanding of this critical issue. This study aimed to address this gap by determining the prevalence, characteristics of DRPs and identifying factors associated with their occurrence.

Methods

During a non-consecutive 48-month study period, a retrospective analysis was conducted to investigate DRPs and the interventions carried out by pharmacists for patients undergoing cardiovascular surgery. The study collected data on patient demographics, clinical characteristics, and pharmacist interventions.

Results

A comprehensive data analysis revealed 671 DRPs among the 623 hospitalized patients, averaging 1.08 DRPs per patient. The most prevalent type of DRPs observed was “Unnecessary drug-treatment P3.2”, accounting for 56.18% (377/671). The primary cause of DRPs was drug selection (C1), followed by dose selection (C3). Pharmacists proposed 1,628 interventions, averaging 2.43 interventions per DRP and 2.61 interventions per patient. Most interventions were accepted and fully implemented by physicians or patients, resulting in 537 (80.03%) of the total DRPs resolved. Furthermore, binary logistic regression analysis demonstrated that the frequency of DRPs was correlated with age, the length of hospitalization, diagnosis of valvular disease, presence of infectious desease and the number of different types of drugs used by the patients.

Conclusions

DRPs are a prevalent issue within the cardiovascular surgery unit, mainly due to drug selection. Clinical pharmacists’ presence has proven effective in mitigating and preventing DRPs, thus optimizing medication therapy.

Introduction

Drug-related problems (DRPs) has gained recognition since the 1990s. DRPs is any event that interferes with a patient’s pharmacotherapy and, consequently, leads to or possible leads to undesirable clinical outcomes. DRPs can occur everywhere, inpatient or outpatient, in every ward where drug therapy is applied for prevention, diagnosis, or management of the disease [1, 2].

The Pharmaceutical Care Network Europe (PCNE) classification system provides a comprehensive subclassification, including types, causes, interventions, and outcomes of DRPs. The current version, V9.0, was developed during an expert seminar in February 2019 and aligned with the V8 version with adaptive adjustments. This classification has been used in various settings, such as in outpatient, inpatient, and community settings [1, 2].

Increased numbers of DRPs may cause increased cost of treatment, prolonged hospital stay, ineffective drug treatment, and increased morbidity or even mortality [3, 4]. Not being exposed to DRPs was associated with a higher chance of reaching the clinical target, of having a better physical quality of life and having lower total health care costs among cardiovascular patients [5].

The prevalence of cardiovascular disease in China is increasing, with alarming implications for public health. Patients undergoing cardiac surgery are at high risk for DRPs due to comorbidities, polypharmacy, and complexity of drug treatment. These problems are most of the time preventable with multidisciplinary team incorporation during the patient care process [5, 6]. Pharmaceutical care encompasses the prevention, identification, and resolution of DRPs, vital components of optimizing patient outcomes and improving their quality of life. To achieve this goal, clinical pharmacists collaborate with other healthcare providers to form multidisciplinary teams (MDT) to provide comprehensive care in cardiovascular surgery units. Through vigilant monitoring of DRPs and the implementation of appropriate interventions, clinical pharmacists are assuming an increasingly significant role in enhancing the effectiveness and safety of drug treatment [6,7,8,9].

However, there has been no research on the state of DRPs and pharmacist interventions in cardiovascular surgery patients in China. This study used the PCNE classification (version 9.0) to analyze the DRPs encountered by patients undergoing cardiovascular surgery. Additionally, we investigated the interventions conducted by clinical pharmacists in addressing these DRPs. The findings of this study aim to contribute valuable information to improve the identification and resolution of DRPs in cardiovascular surgery patients.

Methods

Setting and design

This retrospective cohort study was conducted at The First Hospital of Lanzhou University from 2018.1.1 to 2021.12.31. The hospital is a 2,209-bed tertiary hospital in northwest China. The study focused on the Cardiovascular Surgery Ward (65 beds) and the Interventional Medicine Ward (59 beds). The inclusion criteria were patients 18 years or older who had spent at least one night in the wards and under the care of a MDT consisting of physicians, nurses, and a clinical pharmacist. Patients without pharmaceutical care by the clinical pharmacist would be excluded. This study was approved by the ethics committee of the First Hospital of Lanzhou University as an exempt study (approval number LDYYLL2023-420, approval date 2023.9.18).

Pharmacist’s clinical activities

The clinical pharmacist in the MDT team had completed residency training accredited by the China Ministry of Health. The clinical pharmacist’s responsibilities within the MDT included: (1) active participation in daily MDT rounds and case discussions; (2) providing drug information and therapy consultations to the MDT; (3) reviewing medication orders with the help of a pre-order review system to identify DRPs and proposing appropriate clinical interventions to address these DRPs; (4) identifying and reporting adverse drug reactions for further evaluation and management; and (5) conducting discharge education to ensure proper understanding of medication regimens and adherence.

The categorization of drug-related problems and data collection

The PCNE DRP classification system (version 9.00, 2019) was used to document the types of DRPs, their causes, interventions, and outcomes [3, 4]. The PCNE DRP classification system consists of five components: Problem (P), Cause (C), Planned Intervention (I), Intervention Acceptance (A), and the Status of the DRP (O). Each problem identified (P) may have multiple causes (C) and can result in more than one intervention (I). However, only one outcome (O) is associated with each DRP. The identified DRPs were verified with the MDT, and appropriate pharmacy interventions to address the identified DRPs were discussed and agreed upon by the MDT. The clinical pharmacist evaluated the outcome of each recommended intervention. The results were confirmed by the physicians involved in patient care. This collaborative approach ensured a comprehensive assessment and effective resolution of the identified DRPs.

Baseline demographic and clinical information was collected for each participant through medication records. The following data were obtained: sex, age, smoking and drinking habits, body mass index (BMI), length of stay, admission diagnosis, concomitant diseases, class of medications, and number of drugs used.

Statistical analysis

Patients were divided into the DRP group and the non-DRP group. Descriptive analysis was performed on the patients’ demographics, clinical characteristics, the types, causes, interventions, and outcomes of the DRPs. Continuous variables are presented as inter-quartile range (IQR). Categorical variables are presented using numbers and percentages. Mann–Whitney test was used for statistical significance in continuous data, and Chi-square test was used to determine statistical significance in categorical data. Binary logistic regression analysis was performed to determine the factors associated with the occurrence of DRPs. All variables with a p-value less than 0.1 were included in the regression model. All statistical analyses were performed with SPSS (version 26.0), and the statistical significance was p < 0.05.

Results

Patient characteristics

During the 48-month study period, 623 eligible patients were included in the analysis. Among these patients, 365 (58.59%) experienced DRPs. The median age of the patients was 57 years. Approximately 50.88% of the patients were male. Based on the International Classification of Diseases 10 (ICD-10), the most common admission diagnosis among patients was valvular disease (36.76%), followed by aortic dissection (21.03%) and hypertension (23.76%). The most prevalent comorbidities included infectious diseases (9.15%), respiratory diseases (7.06%), and tumors (5.14%). The top five categories of medications used by the patients were anticoagulants (67.90%), digestive system medications (65.81%), anti-infective medications (58.75%), respiratory medications (56.34%), and traditional Chinese medicines (TCM, 51.20%). Details are shown in Table 1 and Supplementary Table S1.

Table 1 Patient demographic and disease characteristics

Types of drug-related problems identified

A total of 671 DRPs were identified, resulting in an average of 1.08 DRPs per patient (Table 2). Most DRPs were labeled “Others P3,” accounting for 83.45% (560/671). The next most common type was “Treatment Safety P2,” comprising 14.01% (94/671) of the DRPs. Within the category “Others P3”, the primary type was related to Unnecessary drug-treatment (P3.2). In the “Treatment Safety P2” category, the main contributing factor was the occurrence or possibility of adverse drug events (P2.1).

Table 2 Types of drug-related problems and pharmacists’ interventions and outcomes according to the Pharmaceutical Care Network Europe DRP classification tool V9.00

Pharmacists’ interventions to solve the drug-related problems

The pharmacist proposed 1,628 interventions, with an average of 2.43 per DRP identified and 2.61 interventions per patient (Table 2). Most interventions occurred at the prescriber level (I1), representing 35.44% (577/1,628). This was followed by interventions at the drug level (I3), comprising 34.64% (564/1,628), and interventions at the patient level (I2), accounting for 23.52% (383/1,628). Within the drug-level interventions (I3), the primary subcategory was proposing a change in the drug being used (I3.1). At the prescriber level (I1), the primary subcategory was the prescriber asking for additional information (I1.2). In the case of the patient level (I2), the main subcategory was communication with the family member or caregiver (I2.4). 85.87% (1398/1,628) of the proposed interventions were accepted and fully implemented by physicians or patients, resulting in the complete and partial resolution of 90.01% (604/671) of the identified DRPs (Table 2).

Causes of drug-related problems identified

A total of 737 causes of DRPs were identified and categorized (Table 3). The primary cause of DRPs was “Drug selection C1,” accounting for 60.52% (446/737), followed by “Dose selection C3” which accounted for 24.02% (177/737) of the causes. Within the category of “Dose selection C3”, the main subclass contributing to DRPs was a dosage regimen that was too frequent (C3.4), followed by the drug dose being too high (C3.2). In the case of “Drug selection C1,” the main subclass was inappropriate drug selection according to guidelines or formulary (C1.1).

Table 3 Identified causes according to the Pharmaceutical Care Network Europe DRP classification tool V9.00

Analysis of factors associated with the occurrence of DRPs

Compared to patients without DRPs, those with DRPs were significantly older [median of 58.0 (IQR 51,66) vs. 57 (IQR 48,65), respectively] (p = 0.0453). Patients with DRPs had a higher incidence of smoking and drinking history, but significant difference did not achieve. The median of hospital stay for all patients was 16 (10,26) days. Although patients with DRPs tended to have longer hospital stays, this difference did not reach statistical significance either (Table 1).

Patients with DRPs were more likely to have valvular disease, aortic dissection, atrial fibrillation, and infectious diseases as their admission diagnoses (Table 1). They also used more digestive system drugs, liver protective medications, prostaglandins and TCM than patients without DRPs (p < 0.05) (Supplementary Table S1). The number of medications taken by patients with DRPs was higher than in the non-DRP group [median of 8.0 (IQR 6,12) vs. 7.0 (IQR 4,11), respectively] (p = 0.0287)(Table 1).

Before performing a binary logistic regression analysis, a multiple collinearity assessment was conducted on 29 variables derived from the univariate analysis. The results did not show evidence of multicollinearity since all the values of the variance inflation factor (VIF) were less than 10. Subsequently, binary logistic regression analysis revealed that age, hospital stay, diagnosis of valvular disease, presence of infectious desease and the number of different types of drugs used were correlated with the frequency of DRPs (Table 4).

Table 4 Multiple logistic regression analysis of factors associated with the occurrence of DRPs

Discussion

This retrospective study is the first conducted in China to classify and evaluate DRPs in interventional medicine and cardiac surgery units using the PCNE classification system. DRPs are relatively common in these wards, with 58.59% of patients experiencing DRPs, averaging 1.08 DRPs per patient. The prevalence of DRPs was previously reported at 76–100% in cardiovascular surgery wards of which 1.14–2.75 per patient occurred [6, 9,10,11]. In comparison, a study in the cardiovascular surgery ward of University Hospital Zurich found an average of 1.14 DRPs per patient [6]. A study conducted at Hacettepe University Hospitals’ Department of Cardiovascular Surgery reported an average of 2.75 DRPs per patient during the observational period, whereas the rate was 2.15 DRPs per patient in the interventional period [11]. The frequency of DRPs in this study was lower than that reported in other studies carried out in cardiovascular surgery wards, where more than 76% of patients had at least one DRP [6, 9]. These variations in the prevalence of DRPs between different studies can be attributed to several factors, including the size and characteristics of the study population, the duration of the study, the specific definition of DRPs, the classification system used, and differences in drug use patterns and adherence to clinical guidelines [6, 9,10,11].

The main types of DRPs observed in our study were unnecessary drug treatment, treatment cost-effectiveness, and treatment safety. These findings contrast with studies conducted in Brazil and Egypt, where untreated cases were identified as the primary types of DRPs [12, 13]. These results highlight Chinese clinical pharmacists’ important role in ensuring the safe use of medications, reducing the financial burden on patients, and facilitating health insurance audits.

We identified the most common causes of DRPs that may result in pharmacists’ intervention in cardiac surgery: (1) inappropriate drug according to the guidelines /formulary (C1.1), including using TCMs, which may not be recommended as first-line drugs in the guidelines. Cancer patients in interventional medicine are often prescribed drugs not recommended by the guidelines; (2) no indication for drugs (C1.3): examples included the use of proton pump inhibitors (PPIs) without prophylactic indication, inappropriate preoperative preventive use of antibiotics, and the use of unnecessary nutritional drugs; (3) inappropriate duplications of therapeutic group or active ingredient (C1.5): this included the repeated use of TCM, PPIs, and other digestive system medications; (4) too many drugs prescribed for a specific indication (C1.7): for example, the use of multiple medications for preoperative airway management and prescribing a combination of anti-hepatitis drugs without proper justification can lead to unnecessary polypharmacy and potential drug interactions; (5) Drug dose too high (C3.2): a therapeutic dose of antibiotics was prescribed instead of a prophylaxis dose for perioperative prophylaxis use; and (6) duration of treatment too long (C4.2): this could be observed in cases where the preoperative course of antibiotic treatment extended beyond seven days or when the bridging period between anticoagulant medications such as heparin and warfarin was excessively long. These DRPs cause highlight inappropriate medication use and prescribing practices in cardiac surgery, emphasizing the importance of optimizing drug therapy to enhance patient outcomes and reduce healthcare costs.

The results of binary logistic regression analysis indicated that several factors were associated with DRPs, including age, length of hospitalization, diagnosis of valvular disease, presence of infectious desease and the number of different types of drugs used. Our analysis revealed that age was a significant predictor of DRPs, which is consistent with the findings reported in previous studies [12,13,14]. The number of drugs is considerably more important in causing DRPs as compared to age. It may be related to the increased risk of occurring adverse reactions for each new drug added in the treatment, as well as the greater potential of drug interactions. With regard to length of hospitalization, it relates to DRP in two different ways. A longer stay often requires the indication of new drugs, which may result in a new DRP. And in turn the occurrence of DRP may prolong hospitalization due to its management.

Our study has several limitations. First, this study was conducted in a single-center setting. Due to the specialization of the departments, our sample may not encompass the entire spectrum of cardiovascular diseases in interventional medicine and cardiac surgery. Therefore, caution should be exercised when generalizing our findings to other hospitals or patient populations. Second, the drug review process in our study was conducted solely by a clinical pharmacist. Third, our study focused on identifying and categorizing DRPs but did not evaluate the clinical outcome of DRPs and long-term patient outcomes associated with the resolution of these DRPs. More research is needed to explore the potential relationship between DRP resolution and long-term patient outcomes.

Conclusions

The prevalence of DRPs was high in cardiovascular surgery units. The findings emphasize the importance of comprehensive medication management and the need for continuous evaluation and improvement of prescribing practices to minimize the occurrence of DRPs in clinical settings.