Adverse drug events caused by three high-risk drug-drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study.

AIMS: Knowledge about adverse drug events caused by drug-drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+ ) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. METHODS: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. RESULTS: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). CONCLUSION: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.

What is the aetiology of dysnatraemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, retrospective observational study in 11 Dutch hospitals.

OBJECTIVES: To evaluate the relationship among dysnatraemia at hospital presentation and duration of admission, risk of intensive care unit (ICU) admission and all-cause mortality and to assess the underlying pathophysiological mechanism of hyponatraemia in patients with COVID-19. Our hypothesis is that both hyponatraemia and hypernatraemia at presentation are associated with adverse outcomes. DESIGN: Observational study. SETTING: Secondary care; 11 Dutch hospitals (2 university and 9 general hospitals). PARTICIPANTS: An analysis was performed within the retrospective multicentre cohort study COVIDPredict. 7811 patients were included (60% men, 40% women) between 24 February 2020 and 9 August 2022. Patients who were ≥18 years with PCR-confirmed COVID-19 or CT with COVID-19 reporting and data system score≥4 and alternative diagnosis were included. Patients were excluded when serum sodium levels at presentation were not registered in the database or when they had been transferred from another participating hospital. OUTCOME MEASURES: We studied demographics, medical history, symptoms and outcomes. Patients were stratified according to serum sodium concentration and urinary sodium excretion. RESULTS: Hyponatraemia was present in 2677 (34.2%) patients and hypernatraemia in 126 (1.6%) patients. Patients with hyponatraemia presented more frequently with diarrhoea, lower blood pressure and tachycardia. Hyponatraemia was, despite a higher risk for ICU admission (OR 1.27 (1.11-1.46; p<0.001)), not associated with mortality or the risk for intubation. Patients with hypernatraemia had higher mortality rates (OR 2.25 (1.49-3.41; p<0.001)) and were at risk for ICU admission (OR 2.89 (1.83-4.58)) and intubation (OR 2.95 (1.83-4.74)). CONCLUSIONS: Hypernatraemia at presentation was associated with adverse outcomes in patients with COVID-19. Hypovolaemic hyponatraemia was found to be the most common aetiology of hyponatraemia. Hyponatraemia of unknown aetiology was associated with a higher risk for ICU admission and intubation and longer duration of admission.