Elsevier

Journal of Critical Care

Volume 43, February 2018, Pages 1-6
Journal of Critical Care

Clinical Potpourri
Risk factors for potential drug-drug interactions in intensive care unit patients

https://doi.org/10.1016/j.jcrc.2017.08.021Get rights and content

Highlights

  • The rate of the DDIs in ICU patients at a tertiary care hospital is high.

  • Drug related risk factors for DDIs: antiarrhythmics, anticonvulsants, number of prescribed drugs and therapeutic groups.

  • Patient related risk factors for DDIs: higher Charlson Comorbidity Index, male sex, length of hospitalization and surgery.

  • Presence of delirium or dementia and transfer from emergency department to ICU seem to protect against DDIs.

  • The most frequently detected DDI was between midazolam and tramadol.

Abstract

Purpose

To determine risk factors for each severity-based category of potential drug-drug interactions (DDIs) encountered at intensive care unit (ICU) patients.

Methods

This was a retrospective cohort analysis of patients treated at the ICU of the Clinical Center Kragujevac, a public tertiary care hospital in Kragujevac, Serbia. Three interaction checkers were used to reveal drug-drug interactions: Medscape, Epocrates and Micromedex.

Results

The study included 201 patients, 66.19 ± 16.11 years of age. Average number of DDIs per patient ranged from 10.49 ± 8.80 (Micromedex) to 29.43 ± 21.51 (Medscape). Antiarrhythmic or anticonvulsant drug prescription, Charlson Comorbidity Index, male sex, length of hospitalization, number of drugs or therapeutic groups prescribed and surgery increased the risk of DDIs in ICU patients, while presence of delirium or dementia and transfer from emergency department to ICU protected against.

Conclusions

The rate of the DDIs in ICU patients at a tertiary care hospital is high, and adversely influenced by number of drugs or drug groups prescribed per patient, antiarrhythmic or anticonvulsant drug prescription, comorbidities, length of hospitalization and surgery. On the other hand, presence of cognitive deficit and transfer from emergency department to ICU protect ICU patients from the DDIs.

Introduction

Drug-drug interactions (DDIs) implicate changes in a drug's intended or adverse effects due to recent or concurrent use of another drug or drugs. There are several classifications of drug-drug interactions and one of the most important is the one according to severity: drug-drug interactions could be contraindicated, major, moderate and minor [1]. In order to detect and analyze suspected drug-drug interactions clinicians and researchers nowadays frequently use different computer platforms - personal digital assistant software programs [2]. These computer platforms are in the form of databases which can be updated regularly [3]. There are several online databases for detection and analyzing drug-drug interactions, like Micromedex [4], Lexi-Interact [5], Epocrates [6] or Medscape [7]. However, it is important to note that all of these databases have some shortcomings and discrepancies, especially in regard to classification of interactions according to severity, so it is advisable to use more than one database for checking drug-drug interactions [2].

Patients in intensive care units (ICUs) usually have severe and life-threatening illnesses so they frequently receive complex pharmacotherapy with large number of different drugs [8]. On average patients in intensive care unit are receiving 15 different drugs [9], which puts them under high risk of drug-drug interactions [10]. Incidence of clinically significant drug-drug interactions in tertiary health institutions is as high as 54%, whereas average number of interactions per patient is 1.7 [11]. Consequences of drug-drug interactions could be serious, like potentiation of side effects or increase in the toxicity of interacting drugs [9], [10], [11], [12]. Drug-drug interactions are responsible for 5%–9% of all adverse drug reactions in hospitalized patients [13]. It is also known that drug-drug interactions contribute to increased morbidity and mortality of patients in ICUs [8].

Drug-drug interactions are more frequent in patients who are elderly, hospitalized for longer period of time, receive more drugs per day [14], and have severe comorbidities [15]. In addition, higher risk for occurrence of drug-drug interactions is noted in patients who are on antithrombotic and/or anticoagulant therapy [16]. Among the identified risk factors for drug-drug interactions in patients of ICUs, large number of prescribed drugs per day, prolonged stay in intensive care unit and pharmacokinetic/pharmacodynamics characteristics of the administered drugs are supported with the largest body of evidence [17], [18], [19], [20], [21]. However, previous studies which examined the risk factors for the occurrence of interactions did not pay particular attention to the severity of interactions, but concentrated mostly on risk factors for drug-drug interactions in general. This study was designed to determine risk factors for each severity-based category of drug-drug interactions encountered at ICU patients in a tertiary care hospital.

Section snippets

Methods

Our study was designed as retrospective cohort analysis of patients treated at the Intensive Care Unit of the Clinical Center Kragujevac (CCK), a public tertiary care hospital in Kragujevac, Serbia. The cohort consisted of all consecutive patients who were admitted to the 14-beds central ICU between July the 1st 2016 and December the 31st 2016. The Ethics Committee of Clinical Center Kragujevac had approved the study prior to its initiation.

The data that are used for the study were collected

Results

The study included 201 patients who were hospitalized in the ICU. Characteristics of the patients are shown in the Table 1. Only two patients (1%) didn't have a single drug-drug interaction detected by any of the used interaction checkers. Average number of potential drug-drug interactions detected by each of the interaction checkers is shown in the Table 2. The largest number of potential drug-drug interactions was detected by Medscape, followed by Epocrates and Micromedex.

Results of the last

Discussion

Our study showed that antiarrhythmic drugs, anticonvulsants, Charlson Comorbidity Index, male sex, length of hospitalization, number of different therapeutic groups prescribed, number of prescribed drugs and surgery increase the risk of DDIs in ICU patients, while presence of delirium or dementia and transfer from emergency department to ICU protect against them. There is also one factor whose influence is equivocal, i.e. it depends on the interaction checker used: number of physicians who

Acknowledgments

This study was partially supported by bilateral scientific project between Serbia and Montenegro entitled “Risk factors for DDIs in tertiary care hospitals.”

References (40)

  • Lexi-Comp OnlineTM

    Pediatric Lexi-Drugs OnlineTM, Hudson, Ohio: Lexi-Comp, Inc.; 2017

  • Epocrates, Inc

    Interaction checker

  • Medscape

    Multi-drug interaction checker

  • P.L. Smithburger et al.

    Drug-drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved

    Int J Pharm Pract

    (2012)
  • M.M. Alvim et al.

    Adverse events caused by potential drug-drug interactions in an intensive care unit of a teaching hospital

    Rev Bras Ter Intensiva

    (2015)
  • M. Ismail et al.

    Potential drug-drug interactions in medical intensive care unit of a tertiary care hospital in Pakistan

    Int J Clin Pharmacol

    (2016)
  • E.V. Uijtendaal et al.

    Analysis of potential drug-drug interactions in medical intensive care unit patients

    Pharmacotherapy

    (2014)
  • M. Askari et al.

    Frequency and nature of drug-drug interactions in the intensive care unit

    Pharmacoepidemiol Drug Saf

    (2013)
  • R. Fijn et al.

    Hospital prescribing errors: epidemiological assessment of predictors

    Br J Clin Pharmacol

    (2002)
  • A. Ahmad et al.

    Evaluation of potential drug-drug interactions in general medicine ward of teaching hospital in southern India

    J Clin Diagn Res

    (2015)
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