Monitoring drug therapy in hospitalized patients

Prevention of adverse drug events that may result from medication errors is challenging. The safety of medication treatment is mostly determined on an average population and medication errors may be prevented when pharmacotherapy is better tailored to the individualized needs of the hospitalized patients. Especially the stages of prescribing and monitoring of the medication management process have shown to be prone for errors. This thesis therefore describes the frequency and potential clinical relevance of drug therapy monitoring with laboratory markers in hospitalized patients with special focus on potential drug-drug interactions (pDDIs), potassium and ICU patients. The frequency, nature and determinants of pDDIs were determined in both general hospital population and intensive care unit (ICU) patients. pDDIs occurred in 54% of the ICU patients and in 25% of the patients hospitalized at general departments. In both settings, the top-10 drug-drug pairs were responsible for the majority of the pDDI alerts, i.e. for 53% of the pDDI alerts in general departments and for 79% at the ICU. The most frequently occurring possible outcome was an increased risk of side effects and the most frequently advised risk mitigation strategy was laboratory monitoring. Three laboratory markers that are often involved in clinical risk management of drug therapy, serum potassium, sodium and creatinine levels were measured in approximately 50% of the hospitalized patients. Patient related factors appeared to be stronger predictors for monitoring than the use of specific medications. Only when medication was used with an intended effect on electrolytes, measurement was performed more frequently. The percentage of patients with a measurement within the last 48 hours before discharge was less than 25%, suggesting that there is room for improvement in the communication of relevant laboratory values at transition of care. Compared to patients using only one serum potassium increasing drug, serum potassium levels were measured slightly more frequent in patients using two or more serum potassium increasing drugs concomitantly (67% vs 58%). Although prescribers received a direct pop-up to monitor serum potassium levels, serum potassium levels were not measured in 33% of the patients and 10% of the patients developed hyperkalemia. When patients were using both a potassium increasing (PID) and potassium decreasing drug (PDD), and the potassium lowering drug was stopped, serum potassium levels increased in 59% of the patients and 3.2% developed a hyperkalemia (potassium>5.5 mmol/L). When the potassium increasing drug was stopped, serum potassium levels decreased in 70% of the patients and 17% developed a hypokalemia (potassium<3.5 mmol/L). Insulin that is used in tight glucose protocols (TGC) on the ICU may also influence serum potassium levels but TGC was not associated with an increased risk of hypokalemia. High and low mean serum glucose and potassium levels and high variability, however, were associated with an increased ICU mortality. All studies show the importance of laboratory monitoring as a risk mitigation strategy in drug therapy. Patient safety may therefore be optimized when laboratory markers are included in the risk mitigation strategies of clinical decision support systems on medications.