Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study

Bakker, Tinka; Abu‐Hanna, Ameen; Dongelmans, Dave A.; Vermeijden, Wytze J.; Bosman, Rob J.; Lange, Dylan W. de; Klopotowska, Joanna E.; Keizer, Nicolette F. de; Hendriks, Stefaan H. A.; Cate, J.T.M. Houwink Ten; Schütte, Peter; Balen, D. van; Duyvendak, Michiel; Karakus, Attila; Sigtermans, M.; Kuck, E. M.; Hunfeld, Nicole; Sijs, Heleen van der; Feiter, Peter W. de; Wils, Evert‐Jan; Spronk, PE; Kan, H. J. M. van; Steen, Michael; Purmer, Ilse M.; Bosma, B.E.; Kieft, Hans; Marum, Rob J. van; Jonge, Evert de; Beishuizen, Albertus; Movig, Kris L. L.; Mulder, F.; Franssen, Eric J. F.; Bergh, Walter M. van den; Bult, Wouter; Hoeksema, M.; Wesselink, Elsbeth

doi:10.1016/j.jcrc.2020.11.020

Cited by 24 publications

(27 citation statements)

References 19 publications

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“…Among all substances that have been recorded in the database three substance classes, namely macrolides, antifungals, and fluoroquinolones were involved in about 76% of all documented DDIs and in 85% of all by our experts clinically relevant rated DDIs. This is in line with several other studies that investigated relevant DDIs in critically ill patients where the same substance classes have been reported as being highly relevant or frequently causing adverse effects [ 4 , 6 , 73 ]. This parallelism in findings may be due to the nature of the interactions, i.e., the P-gp and/or CYP interaction potential [ 74 , 75 ].…”

Section: Discussionsupporting

confidence: 91%

“…Two recent reviews reported a prevalence of DDIs between 58-67% during ICU stays [4,5]. Due to the patients' critical condition and continuous monitoring in the ICU, not all DDIs are considered clinically Antibiotics 2021, 10, 1330 2 of 17 relevant [6]. However, 38% of ICU patients will experience at least one clinically relevant DDI during their ICU stay [6].…”

Section: Introductionmentioning

confidence: 99%

“…Due to the patients’ critical condition and continuous monitoring in the ICU, not all DDIs are considered clinically relevant [ 6 ]. However, 38% of ICU patients will experience at least one clinically relevant DDI during their ICU stay [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Clinically Relevant Interactions with Anti-Infectives on Intensive Care Units—A Multicenter Delphi Study

et al. 2021

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Patients in intensive care units (ICUs) are at high risk of drug–drug interactions (DDIs) due to polypharmacy. Little is known about type and frequency of DDIs within German ICUs. Clinical pharmacists’ interventions (PI) recorded in a national database (ADKA-DokuPIK) were filtered for ICU patients. Binary DDIs involving ≥1 anti-infective agent with >1 database entry were selected. A modified two-step Delphi process with a group of senior hospital pharmacists was employed to evaluate selected DDIs for clinical relevance by using a five-point scale and to develop guidance for clinical practice. In total, 16,173 PI were recorded, including 1836 (11%) DDIs in the ICU setting. Of the latter, 41% (756/1836) included ≥1 anti-infective agent, 32% (590/1836) were binary DDIs, and 25% (455/1836) were listed at least twice. This translates into 88 different DDIs, 74% (65/88) of which were rated as being clinically relevant by our expert panel. The majority of DDIs (76% [67/88]) included macrolides, antifungals, or fluoroquinolones. This percentage was even higher in DDIs being rated as clinically relevant by the experts (85% [55/65]). It is noted that an inter-professional discussion and approach is needed in the individual patient management of DDIs. The guidance developed might be a tool for decision support.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Clinically Relevant Interactions with Anti-Infectives on Intensive Care Units—A Multicenter Delphi Study

et al. 2021

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“…First, a short detection period may lead to an underestimation of pDDI frequency. Second, ICU patients are more at risk of a pDDI in the first day(s) of admission 25 . For example, Vanham et al 26 detected pDDIs only on the third admission day.…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, we showed that patients with a minimum LOS of 24 hours have a higher pDDI frequency compared to patients with a shorter LOS. 25 Restrictions on Admission Days. Specify if pDDI detection was restricted to specific admission day(s).…”

Section: Reporting Recommendationsmentioning

confidence: 99%

Heterogeneity in the Identification of Potential Drug‐Drug Interactions in the Intensive Care Unit: A Systematic Review, Critical Appraisal, and Reporting Recommendations

Bakker

Dongelmans

Nabovati

et al. 2022

The Journal of Clinical Pharma

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Patients admitted to the intensive care unit (ICU) are frequently exposed to potential drug‐drug interactions (pDDIs). However, reported frequencies of pDDIs in the ICU vary widely between studies. This can be partly explained by significant variation in their methodological approach. Insight into methodological choices affecting pDDI frequency would allow for improved comparison and synthesis of reported pDDI frequencies. This study aimed to evaluate the association between methodological choices and pDDI frequency and formulate reporting recommendations for pDDI frequency studies in the ICU. The MEDLINE database was searched to identify papers reporting pDDI frequency in ICU patients. For each paper, the pDDI frequency and methodological choices such as pDDI definition and pDDI knowledge base were extracted, and the risk of bias was assessed. Each paper was categorized as reporting a low, medium, or high pDDI frequency. We sought associations between methodological choices and pDDI frequency group. Based on this comparison, reporting recommendations were formulated. Analysis of methodological choices showed significant heterogeneity between studies, and 65% of the studies had a medium to high risk of bias. High risk of bias, small sample size, and use of drug prescriptions instead of administrations were related to a higher pDDI frequency. The findings of this review may support researchers in designing a reliable methodology assessing pDDI frequency in ICU patients. The reporting recommendations may contribute to standardization, comparison, and synthesis of pDDI frequency studies, ultimately improving knowledge about pDDIs in and outside the ICU setting.

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Contextualized Drug–Drug Interaction Management Improves Clinical Utility Compared With Basic Drug–Drug Interaction Management in Hospitalized Patients

Wasylewicz

Burgt

Manten

et al. 2022

Clin Pharma and Therapeutics

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Drug-drug interactions (DDIs) frequently trigger adverse drug events or reduced efficacy. Most DDI alerts, however, are overridden because of irrelevance for the specific patient. Basic DDI clinical decision support (CDS) systems offer limited possibilities for decreasing the number of irrelevant DDI alerts without missing relevant ones. Computerized decision tree rules were designed to context-dependently suppress irrelevant DDI alerts. A crossover study was performed to compare the clinical utility of contextualized and basic DDI management in hospitalized patients. First, a basic DDI-CDS system was used in clinical practice while contextualized DDI alerts were collected in the background. Next, this process was reversed. All medication orders (MOs) from hospitalized patients with at least one DDI alert were included. The following outcome measures were used to assess clinical utility: positive predictive value (PPV), negative predictive value (NPV), number of pharmacy interventions (PIs)/1,000 MOs, and the median time spent on DDI management/1,000 MOs. During the basic DDI management phase 1,919 MOs/day were included, triggering 220 DDI alerts/1,000 MOs; showing 57 basic DDI alerts/1,000 MOs to pharmacy staff; PPV was 2.8% with 1.6 PIs/1,000 MOs costing 37.2 minutes/1,000 MOs. No DDIs were missed by the contextualized CDS system (NPV 100%). During the contextualized DDI management phase 1,853 MOs/day were included, triggering 244 basic DDI alerts/1,000 MOs, showing 9.6 contextualized DDIs/1,000 MOs to pharmacy staff; PPV was 41.4% (P < 0.01), with 4.0 PIs/1,000 MOs (P < 0.01) and 13.7 minutes/1,000 MOs. The clinical utility of contextualized DDI management exceeds that of basic DDI management.

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Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study

Cited by 24 publications

References 19 publications

Clinically Relevant Interactions with Anti-Infectives on Intensive Care Units—A Multicenter Delphi Study

Clinically Relevant Interactions with Anti-Infectives on Intensive Care Units—A Multicenter Delphi Study

Heterogeneity in the Identification of Potential Drug‐Drug Interactions in the Intensive Care Unit: A Systematic Review, Critical Appraisal, and Reporting Recommendations

Contextualized Drug–Drug Interaction Management Improves Clinical Utility Compared With Basic Drug–Drug Interaction Management in Hospitalized Patients

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