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Investigation of interventions to reduce nurses’ medication errors in adult intensive care units: A systematic review

  • Zamzam Mohanna
    Affiliations
    Department of Nursing, School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria, 3010, Australia

    The College of Nursing, Jazan University, Jazan, 45142, Saudi Arabia
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  • Snezana Kusljic
    Affiliations
    Department of Nursing, School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria, 3010, Australia

    The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia
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  • Rebecca Jarden
    Correspondence
    Corresponding author. Department of Nursing, School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria, 3010, Australia.
    Affiliations
    Department of Nursing, School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria, 3010, Australia
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Published:August 02, 2021DOI:https://doi.org/10.1016/j.aucc.2021.05.012

      Abstract

      Background

      Medication errors in adult intensive care units (ICUs) are both frequent and harmful. For nurses, these errors may be multifactorial and multidisciplinary, extending from prescription stage to monitoring of patient response to medication. Therefore, diverse interventions have been developed to optimise the medication process to prevent such errors.

      Objectives

      The objective of this systematic review was to identify research investigating interventions that may be effective in reducing the rate of nurses’ medication errors in adult ICUs.

      Methods

      A systematic search was undertaken of three databases: Cumulative Index of Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, and EMCARE using a combination of key terms related to “medication errors”, “nurses”, “interventions”, and “intensive care units”. The search was limited to studies published in English between 2009 and 2019. Independent screening, quality appraisal, and data extraction were undertaken by two reviewers.

      Results

      A total of 464 records were identified from database searches. Eleven studies met inclusion criteria: ten were quasi-experimental designs and one was a randomised controlled trial. Studies examined six types of interventions: prefilled syringes, barcode-assisted medication administration, an automated dispensing system, nursing education programs, a protocolised program logic form, and a preventive interventions program with protocols and pharmacist-supported supervision and monitoring. Findings revealed that a prefilled syringe, nurses’ education programs, and the protocolised program logic form were most effective in reducing medication errors. For the barcode-assisted medication administration, automated dispensing systems, and a preventive interventions program with protocols and pharmacist-supported supervision and monitoring, results showed wide variability in effectiveness.

      Conclusion

      This review found that the evidence for effective interventions to reduce nurses’ medication errors in adult ICUs is limited, due largely to inconsistencies in research design and methods. Therefore, further studies such as randomised controlled trials focusing on a single intervention are required to provide robust evidence of the effectiveness of interventions.

      Keywords

      1. Background

      The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) defined medication error (ME) as “any preventable event that may cause or lead to inappropriate medication use or patient harm”.
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      • Chanoine S.
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      • Calvino-Gunther S.
      • Tournegros C.
      • Terzi N.
      • et al.
      Interprofessional safety reporting and review of adverse events and medication errors in critical care.
      (p. 549) ME occurs when there is a failure in one or more of the rights of medication administration, including right medication, right patient, right dose, right time, right route, right reason, right documentation, right form, and right response.
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      Nursing student medication errors: a retrospective review.
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      Medication errors: an overview for clinicians.
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      • Liu Y.
      The nine rights of medication administration: an overview.
      Moreover, ME can occur at any stage of the medication process (prescription,
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      Medication errors: definitions and classification.
      ,
      • Hughes R.G.
      • Blegen M.A.
      Medication administration safety.
      transcription,
      • Fahimi F.
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      • Abrishami R.
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      • Mazidi T.
      • Faghihi T.
      • et al.
      Transcription errors observed in a teaching hospital.
      ,
      • Lisby M.
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      • Mainz J.
      Errors in the medication process: frequency, type, and potential clinical consequences.
      preparation,
      • Hermanspann T.
      • van der Linden E.
      • Schoberer M.
      • Fitzner C.
      • Orlikowsky T.
      • Marx G.
      • et al.
      Evaluation to improve the quality of medication preparation and administration in pediatric and adult intensive care units.
      ,
      • Wirtz V.
      • Taxis K.
      • Barber N.
      An observational study of intravenous medication errors in the United Kingdom and in Germany.
      dispensing,
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      • Schifano F.
      • Pezzolesi C.
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      A systematic review of the nature of dispensing errors in hospital pharmacies.
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      Medication errors: the importance of safe dispensing.
      administration
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      Medication administration safety.
      ,
      • Feleke S.A.
      • Mulatu M.A.
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      Medication administration error: magnitude and associated factors among nurses in Ethiopia.
      and documentation,
      • Hartel M.J.
      • Staub L.P.
      • Röder C.
      • Eggli S.
      High incidence of medication documentation errors in a Swiss university hospital due to the handwritten prescription process.
      or monitoring the patient response
      • Wessell A.M.
      • Litvin C.
      • Jenkins R.
      • Nietert P.
      • Nemeth L.S.
      • Ornstein S.
      Medication prescribing and monitoring errors in primary care: a report from the Practice Partner Research Network.
      ), either with adverse events or not.
      • Wittich C.M.
      • Burkle C.M.
      • Lanier W.L.
      Medication errors: an overview for clinicians.
      ,
      • Kruer R.M.
      • Jarrell A.S.
      • Latif A.
      Reducing medication errors in critical care: a multimodal approach.
      According to the NCC MERP,
      The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP)
      NCC MERP index for categorizing medication errors.
      there are nine ME categories starting from events that have the capacity to result in error to error that could result in death.

      1.1 Significance of MEs

      MEs may result in adverse drug events, extended hospital stays, or even death.
      • Berdot S.
      • Roudot M.
      • Schramm C.
      • Katsahian S.
      • Durieux P.
      • Sabatier B.
      Interventions to reduce nurses' medication administration errors in inpatient settings: a systematic review and meta-analysis.
      The World Health Organization reported MEs as one of the most common global patient safety issues and a leading cause of preventable harm in health care. This potentially preventable medication-related harm is a significant problem, not only because it affects patients’ lives but also because of the resulting avoidable and enormous costs to the health sector. The financial costs due to the MEs alone are estimated at US$ 42 billion per year worldwide.
      World Health Organization
      WHO launches global effort to halve medication-related errors in 5 years.
      In Australia, the annual cost of medication-related errors is estimated to be at least $1.2 billion.
      Australian Commission on Safety and Quality in Health Care
      Australia joins international push to halve medication errors.

      1.2 MEs in adult intensive care units

      MEs are more likely to occur and cause harm or death in adult intensive care units (ICUs) than in non-ICU settings.
      • Kruer R.M.
      • Jarrell A.S.
      • Latif A.
      Reducing medication errors in critical care: a multimodal approach.
      This can be attributed to the fact that most of the patients in the ICU are critically ill and require complex levels of care;
      • Garrouste-Orgeas M.
      • Philippart F.
      • Bruel C.
      • Max A.
      • Lau N.
      • Misset B.
      Overview of medical errors and adverse events.
      and any minor medication-related adverse event may result in serious consequences.
      • Kruer R.M.
      • Jarrell A.S.
      • Latif A.
      Reducing medication errors in critical care: a multimodal approach.
      Analysis of voluntarily reported MEs in 537 hospitals identified that MEs in the administration stage were higher than those in all other stages in ICU settings (44%) compared with non-ICU settings (33%); however, rates of MEs were not reported.
      • Latif A.
      • Rawat N.
      • Pustavoitau A.
      • Pronovost P.J.
      • Pham J.C.
      National study on the distribution, causes, and consequences of voluntarily reported medication errors between the ICU and non-ICU settings.
      In ICUs, registered nurses primarily administer medications prescribed by medical practitioners. They can also be involved in transcribing, preparing, dispensing, documenting, and monitoring patients’ responses to medication.
      • Hughes R.G.
      • Blegen M.A.
      Medication administration safety.
      ,
      • Mahmood B.S.
      • Kadhim H.Y.
      Effectiveness of an education program on nurses practices concerning medication errors in Baquba teaching hospital.
      Analysis of the voluntarily reported MEs showed that 26% of the MEs in the ICU were made by nurses, followed by pharmacists (6%) and physicians (5%).
      • Latif A.
      • Rawat N.
      • Pustavoitau A.
      • Pronovost P.J.
      • Pham J.C.
      National study on the distribution, causes, and consequences of voluntarily reported medication errors between the ICU and non-ICU settings.
      The most commonly identified causes of MEs made by nurses have been attributed to nursing knowledge, attention, and workload.
      • Esfahani A.K.
      • Varzaneh F.R.
      • Changiz T.
      The effect of clinical supervision model on high alert medication safety in intensive care units nurses.
      • Lu M.-C.
      • Yu S.
      • Chen I.J.
      • Wang K.-W.K.
      • Wu H.-F.
      • Tang F.-I.
      Nurses' knowledge of high-alert medications: a randomized controlled trial.
      • Shahrokhi A.
      • Ebrahimpour F.
      • Ghodousi A.
      Factors effective on medication errors: a nursing view.
      There are a wide range of risk factors reported that transcend four key areas: (i) individual factors,
      • Latif A.
      • Rawat N.
      • Pustavoitau A.
      • Pronovost P.J.
      • Pham J.C.
      National study on the distribution, causes, and consequences of voluntarily reported medication errors between the ICU and non-ICU settings.
      ,
      • Farzi S.
      • Irajpour A.
      • Saghaei M.
      • Ravaghi H.
      Causes of medication errors in intensive care units from the perspective of healthcare professionals.
      • Frith K.H.
      Medication errors in the intensive care unit: literature review using the seips model.
      • Keers R.N.
      • Williams S.D.
      • Cooke J.
      • Ashcroft D.M.
      Causes of medication administration errors in hospitals: a systematic review of quantitative and qualitative evidence.
      (ii) medication-related factors,
      • Chapuis C.
      • Chanoine S.
      • Colombet L.
      • Calvino-Gunther S.
      • Tournegros C.
      • Terzi N.
      • et al.
      Interprofessional safety reporting and review of adverse events and medication errors in critical care.
      ,
      • Hermanspann T.
      • van der Linden E.
      • Schoberer M.
      • Fitzner C.
      • Orlikowsky T.
      • Marx G.
      • et al.
      Evaluation to improve the quality of medication preparation and administration in pediatric and adult intensive care units.
      ,
      • Kruer R.M.
      • Jarrell A.S.
      • Latif A.
      Reducing medication errors in critical care: a multimodal approach.
      ,
      • Frith K.H.
      Medication errors in the intensive care unit: literature review using the seips model.
      (iii) ICU environmental factors,
      • Farzi S.
      • Irajpour A.
      • Saghaei M.
      • Ravaghi H.
      Causes of medication errors in intensive care units from the perspective of healthcare professionals.
      ,
      • Frith K.H.
      Medication errors in the intensive care unit: literature review using the seips model.
      ,
      • Camiré E.
      • Moyen E.
      • Stelfox H.T.
      Medication errors in critical care: risk factors, prevention and disclosure.
      ,
      • Seynaeve S.
      • Verbrugghe W.
      • Claes B.
      • Vandenplas D.
      • Reyntiens D.
      • Jorens P.G.
      Adverse drug events in intensive care units: a cross-sectional study of prevalence and risk factors.
      and (iv) organisational factors.
      • Farzi S.
      • Irajpour A.
      • Saghaei M.
      • Ravaghi H.
      Causes of medication errors in intensive care units from the perspective of healthcare professionals.
      ,
      • Keers R.N.
      • Williams S.D.
      • Cooke J.
      • Ashcroft D.M.
      Causes of medication administration errors in hospitals: a systematic review of quantitative and qualitative evidence.
      • Camiré E.
      • Moyen E.
      • Stelfox H.T.
      Medication errors in critical care: risk factors, prevention and disclosure.
      • Seynaeve S.
      • Verbrugghe W.
      • Claes B.
      • Vandenplas D.
      • Reyntiens D.
      • Jorens P.G.
      Adverse drug events in intensive care units: a cross-sectional study of prevalence and risk factors.

      1.3 The gap in the research

      Evidence has shown that using simple proactive steps and standard practices such as ensuring medication administration rights,
      • Chu R.Z.
      Simple steps to reduce medication errors.
      and nursing-based interventions (e.g. double check)
      • Douglass A.M.
      • Elder J.
      • Watson R.
      • Kallay T.
      • Kirsh D.
      • Robb W.G.
      • et al.
      A randomized controlled trial on the effect of a double check on the detection of medication errors.
      can mitigate MEs. However, these steps cannot stand alone and should be accompanied by other interventions such as guidelines and organisational policies to add an extra layer of efficiency and safety to the medication process. A number of interventions and preventive strategies have been developed to reduce MEs, including educational training programs, technology-based interventions (e.g., computerised physician order entry), guidelines, medication reconciliation, and pharmacist interventions.
      • Kruer R.M.
      • Jarrell A.S.
      • Latif A.
      Reducing medication errors in critical care: a multimodal approach.
      Although these interventions have been applied to decrease MEs in the adult ICU, they still persist due to the complexities associated with medication administration in the ICU.
      • Chapuis C.
      • Chanoine S.
      • Colombet L.
      • Calvino-Gunther S.
      • Tournegros C.
      • Terzi N.
      • et al.
      Interprofessional safety reporting and review of adverse events and medication errors in critical care.
      ,
      • Keeling P.
      • Scales K.
      • Keeling S.
      • Borthwick M.
      Towards IV drug standardization in critical care.
      To avoid unintended duplication of research, a search for systematic reviews and protocols focusing on interventions to reduce the rate of nurses' MEs in adult ICUs was conducted. Two systematic reviews have been conducted which identified (i) the effectiveness of the interventions to minimise MEs in the ICU among all healthcare providers,
      • Manias E.
      • Williams A.
      • Liew D.
      Interventions to reduce medication errors in adult intensive care: a systematic review.
      and (ii) the prevalence of MEs in critical care units as a primary aim and beneficial interventions as a secondary aim.
      • MacFie C.C.
      • Baudouin S.V.
      • Messer P.B.
      An integrative review of drug errors in critical care.
      Other published reviews and protocols have focused on different objectives, settings, population, or on a particular intervention such as computerised physician order entry. However, no protocol or systematic review was identified that has investigated the effectiveness of interventions in reducing nurses’ MEs in adult ICUs.

      1.4 Objectives

      The objective of this systematic review was to identify research investigating interventions that may be effective in reducing the rate of nurses' MEs in adult ICUs. The specific question the review sought to answer was “What interventions are effective in reducing the rate of nurses’ MEs in adult ICUs?”.

      2. Methods

      This review followed the Joanna Briggs Institute (JBI) methodology for systematic review of effectiveness.
      • Tufanaru C.
      • Munn Z.
      • Aromataris E.
      • Campbell J.
      • Hopp L.
      Joanna Briggs Institute reviewer's manual: Chapter 3: systematic reviews of effectiveness.
      The systematic review method was selected as the framework for this research because it allows the best available primary data to be gathered and combined into one review.
      • Gonzalez I.F.
      • Urrutia G.
      • Alonso-Coello P.
      Focus on: contemporary methods in biostatistics (III): systematic reviews and meta-analysis: scientific rationale and interpretation.
      The systematic review provides a high level of unbiased synthesis of studies that relate to the review question and limits the risk of subjective interpretation, as the article selection, critical evaluation, and data analysis are undertaken in duplicate by independent reviewers.
      • Aromataris E.
      • Pearson A.
      The systematic review: an overview.
      The review title was not registered with JBI reviews due to their restriction to collaboration centres only and was not registered with International Prospective Register of Systematic Reviews (PROSPERO) due to registration restrictions for student projects.

      2.1 Inclusion criteria

      Studies were considered for inclusion if they included nurses working in adult ICUs, measured the effectiveness of interventions in reducing the rate of nurses' MEs as a primary or secondary outcome using any method of data collection (e.g., direct observation, chart review, voluntary reporting, incident reporting [sentinel events], or computer monitoring), and were primary research studies published between 2009 and 2019. This time frame was selected as likely to reflect the most recent medication practices, guidelines, technological advances, and safety interventions. Owing to the lack of translation services, only studies published in English were included. The review considered studies that measured the nurses’ ME rates before and after the implementation of the intervention. The reviewers included randomised controlled trials (RCTs), non-RCTs, controlled before-after study designs, and interrupted time series analyses.

      2.2 Exclusion criteria

      Studies were excluded if they focused on MEs made by non-nursing healthcare professionals, did not identify the rate of MEs in the outcomes, or did not measure or report outcomes for ICUs separately.

      2.3 Search strategy

      Following the three steps from JBI methodology, an initial limited search was conducted to determine keywords using the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE. This contributed to the next step, which was to tailor a search strategy for all databases. Then, an inspection of the reference list of all selected articles for full-text screening and potentially relevant reviews was conducted to determine additional relevant studies.

      2.3.1 Information sources

      A comprehensive electronic search was conducted using different databases including CINAHL, MEDLINE (Ovid), and EMCARE (Ovid) to identify all relevant existing evidence. The key search terms included “Medication Errors”, “Nurses”, “Intensive Care Units”, and “Interventions”. These key terms included all relevant words, synonyms, and expressions for each concept to explore the topic as broadly as possible. Instead of using all types and subtypes of MEs, adj operator was used. The Boolean operator “adj” in MEDLINE and EMCARE and “N” in CINAHL followed by a specified number (“5”) helped to obtain terms in any order with four words or less between them. To search and obtain all related words, the search for keywords of “intervention”, “nurse”, and “medication error” was conducted with an asterisk (∗). Details of the search strategy are available in Supplementary file 1.

      2.4 Study selection

      The citations of all retrieved studies were imported into EndNote X9 software (Clarivate Analytics, PA, USA), followed by the removal of duplicate citations. The remaining citations were exported from EndNote to Covidence online software (Veritas Health Innovation, Melbourne, Australia). Title and abstract screening was then undertaken by two reviewers (Z.M. and R.J.). All studies that met the inclusion criteria were obtained in full text and screened by two independent reviewers (Z.M. and R.J.). Any study that did not match the eligibility criteria was excluded. Consensus was achieved by reviewers (ZM and RJ) regarding study selection through discussion and consultation with a third reviewer (S.K.).

      2.5 Quality assessment

      The included studies were critically evaluated by two independent reviewers (Z.M. and R.J.) to determine the risk of different biases within each study. The assessment of studies was conducted using the standardised critical appraisal tools developed by JBI Meta-Analysis of Statistics Assessment and Review Instruments (JBI-MAStARI) for RCTs and non-RCTs.
      The Joanna Briggs Institute (JBI)
      JBI critical appraisal tools: checklist for randomized controlled trial.
      ,
      The Joanna Briggs Institute (JBI)
      JBI critical appraisal tools: checklist for quasi-experimental studies (non-randomized experimental studies).
      The methodological quality of the studies was rated using the categories of Reilly et al.
      • Reilly R.
      • Evans K.
      • Gomersall J.
      • Gorham G.
      • Peters M.
      • Warren S.
      • et al.
      Effectiveness, cost effectiveness, acceptability and implementation barriers/enablers of chronic kidney disease management programs for Indigenous people in Australia, New Zealand and Canada: a systematic review of mixed evidence.
      (good: at least 80%, moderate: 50%–80%, poor: less than 50%); however, these categories were not used to exclude studies. Levels of effectiveness for evidence from JBI methodology were also used to initially rank study designs.
      • Munn Z.
      • Porritt K.
      • Aromataris E.
      • Lockwood C.
      • Peters M.
      Supporting document for the Joanna Briggs Institute levels of evidence and grades of recommendation.
      Any disagreement between reviewers (Z.M. and R.J.) regarding critical appraisal was resolved through discussion and consultation with a third reviewer (S.K.).

      2.6 Data extraction

      The data were extracted from the included studies using a standardised data extraction instrument developed by JBI-MAStARI (adapted to fit the current systematic review).
      • Tufanaru C.
      • Munn Z.
      • Aromataris E.
      • Campbell J.
      • Hopp L.
      Joanna Briggs Institute reviewer's manual: Chapter 3: systematic reviews of effectiveness.
      ,
      • Munn Z.
      • Tufanaru C.
      • Aromataris E.
      JBI's systematic reviews: data extraction and synthesis.
      The data extraction was performed by two independent reviewers (Z.M. and R.J.) and included the following details: study design, location of study, setting(s), sample size, ME type(s), intervention(s) description, intervention duration, outcome measure of interest, and results. Discrepancies between reviewers (Z.M. and R.J.) regarding data extraction were resolved through discussion and consultation with a third reviewer (S.K.).

      2.7 Data synthesis

      The included studies were assessed for homogeneity (I2 statistic) to determine appropriateness of meta-analyses and statistical pooling according to Higgins and Green,
      • Higgins J.P.
      • Green S.
      Cochrane handbook for systematic reviews of interventions [5.1.0 ].
      and where possible, tabulated statistical summaries are presented using RevMan software (Review Manager, version 5.3., Copenhagen, Cochrane Collaboration, 2014). Attempts were made to assess for publication bias using a funnel plot to evaluate if publication bias has influenced the studies available for the review.
      • Duval S.
      • Tweedie R.
      Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis.

      3. Results

      3.1 Study selection

      A total of 464 potentially relevant citations were identified, and 294 citations remained after removing duplicates. After title and abstract screening, 253 citations were identified as irrelevant to the research topic. The reference lists of the 41 articles and potentially relevant reviews were scanned for any additional relevant studies, and five further studies were identified. The full text of the 41 studies was then examined, and 30 studies were excluded as they did not meet the inclusion criteria. Hence, eleven studies eligible for inclusion remained. Fig. 1 shows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram of the study screening and selecting process.
      Fig. 1
      Fig. 1PRISMA flow diagram showing steps of study selection (adapted from Moher, Liberati, Tetzlaff, & Altman, 2009).

      3.2 Methodological quality and level of evidence

      Only one study was a RCT
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      and ten were quasi-experimental studies; of these, three were prospective controlled preintervention and postintervention studies
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      and seven were studies without a control group at preintervention and postintervention.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      Table 1 shows the critical appraisal outcome for the RCT. The most common source of bias was that nurses and those delivering the intervention were not blind to the intervention assignment (performance bias), as it was difficult or not possible to keep it from them in simulated environments due to the nature of the intervention.
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      The outcome assessors were not blind either, increasing the risk of bias in measuring the outcomes.
      Table 1Results of critical appraisal for a randomised controlled trial.
      RCT studiesQ1Q2Q3Q4Q5Q6Q7Q8Q9Q10Q11Q12Q13Total%Quality
      Burger and Degnan
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      YYYNNNYYYYYYY10/1377M
      %100100100000100100100100100100100
      RCT, randomised controlled trial; N, no; Y, yes; %, percentage.
      Percentages reported are indicative of Y (yes) responses: G (good, at least 80%), M (moderate, 50%–80%), P (poor, less than 50%). Q1 to Q13 refers to the following 13 questions of the Joanna Briggs Institute's critical appraisal checklist for experimental studies (JBI, 2019b): (1) Was true randomization used for assignment of participants to treatment groups?; (2) Was allocation to treatment groups concealed?; (3) Were treatment groups similar at the baseline?; (4) Were participants blind to treatment assignment?; (5) Were those delivering treatment blind to treatment assignment?; (6) Were outcomes assessors blind to treatment assignment?; (7) Were treatment groups treated identically other than the intervention of interest?; (8) Was follow-up complete and if not, were differences between groups in terms of their follow-up adequately described and analysed?; (9) Were participants analysed in the groups to which they were randomized?; (10) Were outcomes measured in the same way for treatment groups?; (11) Were outcomes measured in a reliable way?; (12) Was appropriate statistical analysis used?; (13) Was the trial design appropriate and any deviations from the standard RCT design (individual randomization, parallel groups) accounted for in the conduct and analysis of the trial?
      The critical appraisal for the quasi-experimental studies is reported in Table 2. Only three studies included a control group.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      Only one study implemented multiple measurements at preintervention and postintervention,
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      while the remaining studies did not use multiple measurements, which reduced the rigor of the studies, as it decreases certainty that change in outcomes is related to the intervention and not to other confounding variables. Five studies used multicomponent interventions and did not report them independently, which could compromise the reliability of results (measurement bias). Another bias that was not included in the checklist, but was found to be high risk, is the lack of blinding. In four of the studies, the nurses were blinded to the research objective.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      ,
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      However, in all but the study by Benoit el al.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      , these nurses were aware that they were being observed, which may have impacted on their behaviours (i.e., performance bias). Data collectors were also aware of the studies objectives and comparator groups except for Nguyen et al.,
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      which could have increased the risk of data collection bias. The outcome assessor(s) were reported to be blind only in four studies.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      ,
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      Only one study did not report any information about blinding.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      Table 2Results of critical appraisal for quasi-experimental studies.
      Non-RCT studiesQ1Q2Q3Q4Q5Q6Q7Q8Q9Total%Quality
      DeYoung et al.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      YYYNNYYYY7/978M
      Helmons et al.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      YYYNNYYYY7/978M
      Seibert et al.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      YYYNNYYYY7/978M
      Chapuis et al.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      YYYYNYYYY8/989G
      Ford et al.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      YNYYNYYYY7/978M
      Lohmann et al.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      YYYNNYYNY6/967M
      Nguyen et al.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      YYYYNYYNY7/978M
      Tan et al.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      YYYNNYYNY6/967M
      Benoit et al.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      YYYNYYYNY7/978M
      Romero et al.
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      YYYNNYYNY6/967M
      %10090100301010010050100
      RCT, randomised controlled trial; N, no; Y, yes; %, percentage.
      Percentages reported are indicative of Y (yes) responses: G (good, at least 80%), M (moderate, 50%–80%), P (poor, less than 50%). Q1 to Q9 refers to the following nine questions of the Joanna Briggs Institute's critical appraisal checklist for quasi-experimental studies (JBI, 2019a): (1) Is it clear in the study what is the “cause” and what is the “effect” (i.e. there is no confusion about which variable comes first)?; (2) Were the participants included in any comparisons similar?; (3) Were the participants included in any comparisons receiving similar treatment/care, other than the exposure or intervention of interest?; (4) Was there a control group?; (5) Were there multiple measurements of the outcome both before and after the intervention/exposure?; (6) Was follow-up complete and if not, were differences between groups in terms of their follow-up adequately described and analysed?; (7) Were the outcomes of participants included in any comparisons measured in the same way?; (8) Were outcomes measured in a reliable way?; (9) Was appropriate statistical analysis used?
      All studies have a likelihood of bias, as there is at least one missing element of the study quality indicators on the critical appraisal checklists. Based on levels of evidence for effectiveness from JBI methodology, the eleven studies in this review belong to level 1 and level 2 in the hierarchy.

      3.3 Characteristics of included studies

      3.3.1 Location of studies and publication date

      All included studies were primary research published between 2009 and 2017. Most of these studies were conducted in developed countries based on the classification by the United Nations. Studies were undertaken in the USA (n = 5), Germany (n = 1), France (n = 1), Switzerland (n = 1), Malaysia (n = 1), Vietnam (n = 1), and Chile (n = 1).

      3.3.2 Setting and demographics

      Only Seibert et al.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      conducted their study across two hospitals. Three of the studies were conducted in several settings including the ICU.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      ,
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      ,
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      These studies were still considered valid for inclusion because they measured at least one type of MEs separately for the ICU. The RCT crossover study was conducted in a simulation unit similar to the acute care unit to control or avoid confounding variables that may impact the study outcomes.
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      All eleven studies targeted MEs derived only from the actions of nurses.

      3.3.3 Types of interventions

      Six different types of interventions were identified: prefilled syringes, barcode-assisted medication administration (BCMA), an automated dispensing system (ADS), education programs, a protocolised program logic form, and a preventive interventions program with protocols and pharmacist-supported supervision and monitoring (PIP). Five studies used multicomponent interventions,
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      ,
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      ,
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      ,
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      ,
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      while the others focused on a single intervention. Table 3 shows the description of the intervention and the targeted types and subtypes of MEs for each study.
      Table 3Description of the intervention and the targeted types and subtypes of medication errors for each study.
      StudiesIntervention descriptionME typeME subtypes
      Technology-based interventions
      DeYoung et al.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      BCMA with eMARMAEsWrong drug, wrong administration time, wrong route, wrong dose, administration of a drug with no order, omission, and documentation error.
      Helmons et al.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      BCMA with eMARMAEsOmission, drug not available, wrong dose, wrong technique, unauthorised, and wrong time errors.
      Seibert et al.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      BCMA with eMARMAEsWrong time, wrong route, wrong technique, omission, wrong form, extra dose, and unauthorised drug
      Chapuis et al.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      ADS vs. standard practice system (ADS consists of drawers that contain secured storage compartments, each compartment including a single type of medication, and the access to that cabinets is digitally controlled through fingerprints and/or passwords)Medication picking errors, MPEs, MAEsPicking: name, dosage, and pharmaceutical form

      Preparation: dose, solvent type/volume for reconstitution, and mixtures

      Administration: technique, route, rate, time, and physicochemical incompatibility.
      Nursing education interventions
      Ford et al.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      Simulation-based education vs. didactic lectures

      Case scenarios were used in the intervention group requiring nurses to apply proper administration techniques. If an error was made, the patient-simulator responded to that using variables (e.g. heart rate and blood pressure).
      MAEsWrong drug name, wrong dose, wrong route, wrong time, wrong technique, and drug documenting
      Lohmann et al.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      Composed of four main components:

      (1) Electronic database: information on crushing and suspending solid drugs, the proper solvents, and safety standards

      (2) E-learning tool: general information on feeding tubes and specific information on correct drug preparation and administration

      (3) Poster: information on drug modification for the commonly used drugs prepared in ICU and alternative dosage forms for drugs that could neither be crushed nor suspended.

      (4) Teaching session: covering prevalent MPEs observed during the baseline period
      MPEs for patients with feeding tubesIncorrect crushing and suspending of solid peroral medications and incorrect solvents
      Nguyen et al.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      Composed of three main components:

      (1) Classroom lectures: PowerPoint presentation covering compatibility, reconstitution, administration rate, and drug preparation and administration techniques

      (2) Practical session: covering preparation and administration of commonly used drugs in ICUs

      (3) Posters: on recommended practice for safe drug preparation and administration and guidelines on preparation and administration of commonly used I.V. drugs in ICUs
      I.V MPEs and MAEsWrong drug, wrong dose, wrong dosage form, deteriorated drug, wrong preparation technique, administration omission, unordered drug, and wrong administration technique
      Tan et al.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      Composed of three main components:

      (1) Educational video: practice of parenteral medication preparation and administration processes, information on administration rates, compatibilities, general reconstitution guidelines, and aseptic techniques

      (2) A bookmark-sized memory aid: preparation and administration guide for commonly used parenteral drugs in ICUs and calculation tips

      (3) PowerPoint: the study findings from the baseline period
      Parenteral MPEs and MAEs (I.V, I.M, S.C)Omission, wrong preparation, wrong dose, wrong route, wrong rate, wrong time, incompatibilities, and concentration errors
      Other interventions
      Burger and Degnan
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      Two prefilled syringes (BDS and CJ) vs. TVSP carried out by nurses.

      Three rooms in a simulation centre were set up. Nurses had to prepare three types of drugs in each room (diphenhydramine, ketorolac, and morphine), using one of the three methods of I.V push medication (BDS, CJ, or TVSP) in a random order.
      MPEsWithdrawal CJ using a needle, dilution of the drug into a prefilled flush syringe, failure to label, failure to swab the top of the vial, and misuse of the CJ.
      Benoit et al.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      A protocolised program logic form composed of three main components:

      (1) The form merged order and administration forms into a single document

      (2) Added new sections for start/stop orders and discontinued drugs in a logical sequence

      (3) Preprinted commonly used drugs names, approved units, and fixed routes
      MAEsOmission, not discontinued drugs, wrong frequency, wrong dosage, wrong rate, missed target, wrong route, and wrong drug
      Romero et al.
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      A newly designed preventive interventions program composed of four main components:

      (1) Involving a clinical pharmacist (e.g. educational activities, monitoring, and developing drug-related policies)

      (2) Standardising medication use

      (3) Staff training and motivations by pharmacists

      (4) Creating a ME reporting system.
      All stagesNR
      BCMA, barcode-assisted medication administration (works by scanning the barcode on the patient’s wristband, and on the medication label, then the information is transferred automatically to the electronic medical record system, allowing the nurse to review and compare the orders with the medication being administered); eMAR, electronic medication administration record; ADS, automated dispensing system; MEs, medication errors; MPEs, medication preparation errors; MAEs, medication administration errors; I.V, intravenous; I.M, intramuscular; S.C, subcutaneous; BDS, BD Simplist; CJ, Carpuject; TVSP, traditional vial and syringe preparation; ICU, intensive care unit; NR, not reported.

      3.3.4 Sample size and data collection

      Eight studies met their predetermined sample size requirement to detect statistical significance and three did not.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      ,
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      ,
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      The error rate denominator “total opportunities for error”, which is defined as the number of doses observed or given plus the number of dose omissions,
      • Berdot S.
      • Gillaizeau F.
      • Caruba T.
      • Prognon P.
      • Durieux P.
      • Sabatier B.
      Drug administration errors in hospital inpatients: a systematic review.
      was used by five studies.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      ,
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      ,
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      ,
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      ,
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      Other denominators included the “number of observed doses or medications that were prepared or administered by nurses”,
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      ,
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      ,
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      ,
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      “total number of patients and total number of observations”,
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      and “number of lines of drugs”.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      All the included studies used direct observation to detect MEs, except one study that used a prospective chart review.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.

      3.3.5 Outcomes

      The observation notes taken by the data collectors throughout all included studies were compared with the physician's prescription, manufacturer's instructions, and hospital protocol. Any difference between them was considered an error. The most common measurable outcomes used to report MEs were ME rates. The other studies defined the overall total rate as the percentage of total opportunities for error,
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      the prevalence of clinically relevant errors,
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      ,
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      and the prevalence of patients with one or more MEs.
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      One study used accuracy rates as reported measurable outcome.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      Table 4 shows the description of the eleven studies.
      Table 4Description of the included studies.
      StudyStudy designCountry/setting(s)Sample sizeIntervention periodData collectionData collector
      Medications/doses/TOEsPatientsNurses
      Technology-based intervention
      DeYoung et al.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      Prospective pre–post intervention studyUSA, 38-bed MICU, community teaching hospitalAt preintervention: 775

      At postintervention: 690
      At preintervention: 47

      At postintervention: 45
      NRAt preintervention: 1 M

      At postintervention: 4 M
      DO2 pharmacists, 1 nurse
      Helmons et al.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      Prospective pre–post intervention studyUSA, 13-bed MICU, 20-bed SICU and non-ICUs, academic teaching hospitalAt preintervention: 374

      At postintervention: 394
      NRNRAt preintervention: 1 M

      At postintervention: 3 M
      DO2 pharmacists, 6 pharmacy students
      Seibert et al.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      Pre–post intervention nonequivalent comparison group designUSA, MICU, SICU, and non-ICUs, 2 tertiary care units, community hospitalsAt preintervention: 335

      At postintervention: 65
      NRNRInitial postintervention: 6 M

      Final postintervention: 12 M
      DO7 pharmacists, 8 nurses
      Chapuis et al.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      Controlled pre–post intervention studyFrance, 2 MICUs of 8 and 10 bed, university hospitalCG: preintervention: 300; postintervention: 333

      IG: preintervention 368; postintervention: 475
      CG: preintervention: 31; postintervention: 25

      IG: preintervention: 32; postintervention: 27
      68At preintervention: 2 M

      At postintervention: 2 M
      DO1 pharmacist
      Nursing education interventions
      Ford et al.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      Prospective, parallel controlled pre–post intervention studyUSA, 32-bed MICU (CG) and 10-bed CCU (IG), teaching hospitalCG: preintervention: 159; initial postintervention: 172; final postintervention: 147

      IG: preintervention: 156; initial postintervention: 149; final postintervention: 97
      76CG: preintervention: 12; postintervention: 12

      IG: preintervention: 12; postintervention: 11
      Initial postintervention: 1–4 W

      Final postintervention: 8–12 W
      DO2 pharmacists
      Lohmann et al.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      Prospective pre–post intervention studyGermany, 24-bed gastroenterological ICU and non-ICU, tertiary care university hospitalPreintervention: 514 preparations (396 solid drugs)

      Postintervention: 474 preparations (379 solid drugs)
      NRNRPreintervention: 20 D

      Postintervention: 32 D
      DO1-2 observers
      Nguyen et al.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      Prospective controlled pre–post intervention studyVietnam, ICU (IG) and PSU (CG)CG: preintervention: 280; postintervention: 281

      IG: preintervention: 236; postintervention: 407
      NRNRPreintervention: 2 W

      Postintervention: 3 W
      DO4 senior pharmacy students
      Tan et al.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      Prospective pre–post intervention studyMalaysia, 15-bed GICU, tertiary teaching hospitalPreintervention: 122

      Postintervention: 105
      NRPreintervention: 39

      Postintervention: 35
      Preintervention: 2 M

      Postintervention: 2 M
      DO1 pharmacist
      Other interventions
      Burger and Degnan
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      Randomised crossover simulation studyUSA, simulation centre similar to acute careCG: 72

      IG: 72 in the BDS group and 72 in the CJ group
      NACG: 24

      IG: 24
      1 DDO1 nurse
      Benoit et al.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      Interrupted time series designSwitzerland, ICU, tertiary care teaching hospitalPreintervention: 4626

      Postintervention: 4672
      Preintervention: 144

      Postintervention: 150
      NR85 DChart review1 pharmacist investigator
      Romero et al.
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      Prospective pre–post intervention studyChile, 12-bed MICU and SICU, tertiary care teaching hospitalPreintervention: 194

      Postintervention: 216
      Preintervention: 124

      Postintervention: 154
      NRPostintervention: 6 MDOpharmacists
      ICU, intensive care unit; GICU, general intensive care unit; MICU, medical intensive care unit; SICU, surgical intensive care unit; PSU, post-surgical unit; IG, intervention group; CG, control group; TOE, total opportunities for error; BDS, BD Simplist; CJ, Carpuject; M, month; W, week; D, day; DO, direct observation; NR, not reported; NA, not applicable.

      3.4 Comparison of study findings

      Owing to the extensive heterogeneity in the comparison of ME rates between ten studies included in this review (I2 = 86%), in addition to intervention types, ME types, outcome measures, study design, and risk of bias (i.e., both clinical and methodological diversity), conducting a quantitative meta-analysis was not appropriate. For the same reasons, the assessment of publication bias was not feasible. However, statistical summary and forest plots for ten studies were presented to illustrate the risk ratio (RR) with 95% confidence interval (CI). The statistical summary for one study could not be calculated, as the measurable outcomes were the accuracy rates.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      The forest plot is presented in Fig. 2.
      Fig. 2
      Fig. 2Forest plot and statistical summary of the included studies (n = 10). This figure illustrates that in nine of these ten studies the results favoured the interventions rather than the control. BCMA, barcode-assisted medication administration; ADS, automated dispensing system; EP, education program; PS, prefilled syringe; PPLF, protocolised program logic form; PIP, preventive interventions program with protocols and pharmacist-supported supervision and monitoring; M–H, Mantel-Haenszel; CI, confidence interval.

      3.5 Impact of interventions

      3.5.1 Studies investigating technology-based interventions

      The impact of technology-based interventions was examined in four studies in this review. After the implementation of BCMA, DeYoung et al.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      found that the overall medication administration error rate was significantly reduced by 56% (from 19.7% to 8.7, p < 0.001) (RR = 0.44, 95% CI: [0.33–0.58]). Most errors, which were significantly reduced (18.8% vs. 7.5%, p < 0.001), were related to the wrong administration time. However, other medication administration error types showed an increase or no significant reductions. Helmons et al.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      reported a reduction in medication administration errors in non-ICU settings, but in the ICU, no differences were detected for the overall ME rate (12.6% vs. 13.5%) (RR = 1.07, 95% CI: [0.74–1.54]). Seibert et al.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      showed that the total medication administration accuracy rates after the introduction of BCMA increased in most study settings; however, in ICUs, the medication administration accuracy did not increase. On the contrary, it decreased from 94% to 83%. This would suggest that the medication administration error rate increased from 6% to 17%.
      Only one study included an investigation of the impact of automated dispensing technology.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      After the intervention, the percentage of total opportunities for error in the intervention unit was less than that in the control unit (13.5% vs. 18.6%, p < 0.05); however, RR analysis showed that the reduction did not reach statistical significance (RR = 0.72, 95% CI: [0.53–1.00]). The percentage of detailed analysis shows that medication preparation errors were reduced in the intervention unit (6% vs. 3.4%, p < 0.05), while medication selection errors and medication administration errors were not significantly changed (from 1.8% and 2.8% to 1.5% and 2.7%, respectively). Although errors belonging to category C, which according to the NCC MERP classification indicates no harm, were reduced by 35%, the technology did not decrease those causing harm (categories D to H).

      3.5.2 Studies investigating education programs

      Different types of nurses’ education programs were evaluated in four studies; the outcomes were positive. Ford et al.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      compared simulation-based learning given to 12 coronary critical care nurses with traditional lecture-style education given to 12 medical ICU nurses. In the intervention unit, the medication administration error rates significantly decreased (30.8% vs. 4.0%, p < 0.001) at the initial postintervention and remained at 6.2% in the final postintervention (30.8 vs. 6.2%, p < 0.001). Comparatively, in the control unit, medication administration error rates were not significantly different (20.8% vs. 22.7%, p = 0.672) in the initial postintervention and increased to 36.7% in the final postintervention (p = 0.002). Comparing the initial postintervention for both units, RR analysis showed a significant reduction for the intervention unit (RR = 0.18, 95% CI: [0.08–0.41]). Lohmann et al.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      also found that the implementation of the newly designed educational training programs for the nurses significantly decreased the rate of incorrect preparation of crushing and/or suspending of solid peroral medications for patients with feeding tubes, involving potentially hazardous medications (9.8% vs. 4.2%, p < 0.01) (RR = 0.43, 95% CI: [0.24–0.75]). However, as a secondary aim, the study showed that there was no difference in using inappropriate solvents for solid medications before and after intervention (10.4% vs. 10.6%, p = 0.93).
      Nguyen et al.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      compared a pharmacist-led education and training program delivered to nurses working in the ICU versus nurses working in a postsurgical unit. Following the pharmacist-led training, the prevalence of clinically relevant errors was less in the ICU (64% vs. 48.9%, p < 0.001), although the ME rate remained relatively high. Comparatively, in the control unit, the prevalence of clinically relevant errors was not significantly different (57.9% vs. 64.1%, p = 0.132). Comparing the postintervention results for both units, RR analysis showed a significant reduction for the intervention unit (RR = 0.76, 95% CI: [0.67–0.87]). Tan et al.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      reported that a multicomponent education program for ICU nurses was effective in reducing parenteral medication preparation and administration errors. From the baseline to follow-up, the error rate significantly decreased (79% vs. 50%, p < 0.05) (RR = 0.63, 95% CI: [0.51–0.78]). However, the rates of MEs remained high, despite the reduction reported. The secondary aim of the study, which focused on “concentration errors”, showed no difference before and after intervention (48% vs. 53%).

      3.5.3 Studies investigating other interventions

      The only RCT in this review compared two types of intravenous push prefilled syringes with manually filled syringes by nurses.
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      The study revealed that medication preparation errors were significantly lower when using the industrial Simplist prefilled syringes, compared with both Carpuject prefilled syringes and the traditional vial-and-syringe process carried out by ICU nurses (1.4%, 77.8%, and 73.6% respectively; p < 0.001). Comparing Simplist prefilled syringes with traditional ones, RR analysis showed a significant reduction (RR = 0.02, 95% CI: [0.00–0.13]). After the implementation of a protocolised program logic form by Benoit et al.,
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      a total of 229 errors were found in 4626 lines of drugs (4.95%) at baseline compared with 100 errors in 4672 lines of drugs after intervention (2.14%, p < 0.001), representing a 56.8% relative reduction (RR = 0.43, 95% CI: [0.34–0.54]). In considering the effect of combined interventions of PIP, Romero et al.
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      observed that the prevalence of patients with one or more MEs at all stages was reduced (41.9% vs. 28.6%, p < 0.05), and the ME rate decreased from 34% (66/194) to 25.5% (55/216), p = 0.058. Comparing before and after interventions, ME rate reduction was not significant (RR = 0.75, 95% CI: [0.55–1.01]). However, while the prevalence of patients with MEs decreased by 50% during the administration process (26% vs. 13%), errors during the preparation process were not significantly different (7% vs. 8%). The results of the eleven included studies are reported in Table 5.
      Table 5Data extraction of the included studies.
      StudyMeasurable outcomeFindings/P valueMean change, RR, and 95% CISeverity of harm of MEsLevel of evidence
      Technology-based interventions
      DeYoung et al.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      ME ratePreintervention: 153/775 errors (19.7%)

      Postintervention: 60/690 errors (8.7%) (p < 0.001)

      Wrong time errors: preintervention: 146/775 errors (18.8%), postintervention: 52/690 errors 7.5% (p < 0.001)
      Significant reduction (56%)

      (RR = 0.44, 95% CI [0.33–0.58])

      Wrong time errors reduced by 60% [CR]
      NELevel 2.d
      Helmons et al.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      ME ratePreintervention: 47/374 errors (12.6%)

      Postintervention: 53/394 errors (13.5%)

      P value NR
      No difference (RR = 1.07, 95% CI [0.74–1.54])NELevel 2.d
      Seibert et al.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      Medication accuracy rateAccuracy rate: preintervention: 94%, postintervention: 83%

      ME rate: preintervention: 6%, postintervention: 17%

      P value NR
      ME rate increasedNELevel 2.d
      Chapuis et al.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      %TOE and %DOE%TOE:

      CG: preintervention: 58/300 errors (19.3%), postintervention: 62/333 errors (18.6%)

      IG: preintervention: 75/368 errors (20.4%), postintervention: 64/475 errors (13.5%) (p < 0.01)

      CG vs. IG p < 0.05

      %DOE in IG:

      Preparation errors: 42/695 errors (6%) vs. 26/764 errors (3.4%), p < 0.05

      Picking errors: 8/435 errors (1.8%) vs. 9/595 errors (1.5%)

      Administration errors: 31/1120 errors (2.8%) vs. 33/1240 (2.7%)
      CG vs. IG reduction of 6.2% absolute difference; relative reduction of 27% [CR], not significant (RR = 0.72, 95% CI [0.53–1.00])%DOE:

      Errors not causing harm: CG: 190/6154 (3.1%); IG: 54/2599 (2.1%)

      Errors causing harm: CG: 35/6154 (0.6%); IG: 16/2599 (0.7%)
      Level 2.c
      Nursing education interventions
      Ford et al.
      • Ford D.G.
      • Seybert A.L.
      • Smithburger P.L.
      • Kobulinsky L.R.
      • Samosky J.T.
      • Kane-Gill S.L.
      Impact of simulation-based learning on medication error rates in critically ill patients.
      ME rateCG: preintervention: 33/159 errors (20.8%), initial postintervention: 39/172 errors (22.7%); (p = 0.672), final postintervention: 54/147 errors (36.7%), (pre vs. post p = 0.002)

      IG: preintervention: 48/156 errors (30.8%), initial postintervention: 6/149 errors (4%), (p < 0.001), final postintervention: 6/97 errors (6.2%) (pre vs. post p < 0.001)
      Initial postintervention: CG vs. IG significant reduction (82%) [CR] (RR = 0.18, 95% CI [0.08–0.41])

      Final postintervention: CG vs. IG (83%) [CR]
      NELevel 2.c
      Lohmann et al.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      ME rateInappropriate crushing and/or suspending of solid drugs: preintervention: 39/396 errors (9.8%), postintervention: 16/379 errors (4.2%), (p < 0.01)

      Inappropriate solvents for solid drugs: preintervention: 41/396 errors (10.4%), postintervention: 40/379 errors (10.6%), (p = 0.93)
      Significant reduction (57%) [CR] (RR = 0.43, 95% CI [0.24–0.75])NELevel 2.d
      Nguyen et al.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      Prevalence of clinically relevant errorsCG: preintervention: 162/280 errors (57.9%), postintervention: 180/281 errors (64.1%) (p = 0.132)

      IG: preintervention: 151/236 errors (64%), postintervention: 199/407 errors (48.9%) (p < 0.001)
      CG vs. IG significant reduction (23.7%) [CR] (RR = 0.76, 95% CI [0.67–0.87])NELevel 2.c
      Tan et al.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      ME ratePreintervention: 96/122 (79%)

      Postintervention: 52/105 errors (50%) p < 0.05

      Concentration errors: preintervention: 19/40 errors (48%), postintervention: 8/15 errors (53%) (p = 0.70)
      Significant reduction (36.7%) [CR] (RR = 0.63, 95% CI [0.51–0.78])NELevel 2.d
      Other interventions
      Burger and Degnan
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      ME rateCG: 53/72 errors (73.6%)

      IG: BDS: 1/72 errors (1.4%), CJ: 56/72 errors (77.8%)

      BDS vs. others (p < 0.001)
      Significant reduction (RR = 0.02, 95% CI [0.00–0.13])NELevel 1.c
      Benoit et al.
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      Error rate per line of drug (actual errors)Preintervention: 229/4626 errors (4.95%)

      Postintervention: 100/4672 errors (2.14%) p < 0.001
      Significant reduction (56.8%)

      (RR = 0.43, 95% CI [0.34–0.54])
      NELevel 2.d
      Romero et al.
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      The prevalence of patients with ME and ME rate(1) Patients with MEs at all stages: preintervention: 52/124 errors (41.9%), postintervention: 44/154 (28.6%) p < 0.05

      (2) ME rate at all stages: preintervention: 66/194 (34%), postintervention: 55/216 (25.5%) p = 0.058

      (3) Patients with MEs at administration stage: preintervention: 26%, postintervention: 13%

      (4) Patients with MEs at preparation stage: preintervention: 7%, postintervention: 8%
      (1) Reduced by 31.7%

      (2) Reduced by 25% (RR = 0.75, 95% CI [0.55–1.01])

      (3) Reduced 50%

      (4) No difference
      NELevel 2.d
      IG, intervention group; CG, control group; ADS, automated dispensing system; BCMA, barcode-assisted medication administration; eMAR, electronic medication administration record; BDS, BD Simplist; CJ, Carpuject; MEs, medication errors; %TOE, the percentage of total opportunities for error; %DOE, the percentage of detailed opportunities for error; RR, risk ratio; CI, confidence interval; NE, not examined; CR, calculated by reviewer (was calculated from the reported means by calculating the difference between two numbers [e.g. pre- and post- intervention], then dividing the result by the original number [e.g. preintervention], and finally multiplying the result by 100. This enabled comparison of mean change percentages across studies). Level 1.c represents experimental designs (a randomised controlled trail), level 2.c represents quasi-experimental designs (a quasi-experimental prospectively controlled study), and level 2.d represents quasi-experimental designs (a pretest–post-test or historic/retrospective control group study).

      4. Discussion

      This systematic review is the first study investigating the effect of different interventions developed to decrease the rates of nurses' MEs in adult ICUs. Eleven studies were included, most of which were quasi-experimental in design, while only one study was a RCT. The overall risk of bias of the studies was identified to be high. The observational methodology was adopted by most of the studies, which is considered as the most accurate ME detection tool and reporting method.
      • Meyer-Massetti C.
      • Cheng C.M.
      • Schwappach D.L.B.
      • Paulsen L.
      • Ide B.
      • Meier C.R.
      • et al.
      Systematic review of medication safety assessment methods.
      Observing nurses during medication processes may result in altered behaviour and performance as they are aware that they are being observed; this phenomenon is referred to as the “Hawthorne effect.
      • McCambridge J.
      • Witton J.
      • Elbourne D.R.
      Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects.
      This effect can in turn lead to a major threat to the study's internal validity, which is performance bias.
      • McCambridge J.
      • Witton J.
      • Elbourne D.R.
      Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects.
      Only one study was multicentre, which may compromise the generalisability of results. The difference between the findings could be influenced by different methods, definitions, denominators, and location of the studies.
      • Alsulami Z.
      • Conroy S.
      • Choonara I.
      Medication errors in the Middle East countries: a systematic review of the literature.
      Owing to the variety of interventions, ME types, outcome measures, and study designs, comparing the results of the studies in detail was challenging. All studies that focused on prefilled syringes, nursing education programs, and the protocolised program logic form as interventions showed a significant reduction of the primary targeted type of ME rates. However, findings from quasi-experimental studies without a control group must be interpreted with caution, as they may pose a concern with respect to a lack of randomisation (the major weakness), selection bias, and inability to prevent awareness of participants to the intervention due to the nature of the intervention.
      • Miller C.J.
      • Smith S.N.
      • Pugatch M.
      Experimental and quasi-experimental designs in implementation research.

      4.1 Comparison with other studies

      4.1.1 Technology-based interventions

      This review indicates that the implementation of BCMA and ADSs in ICUs have limited effectiveness on reducing nurses’ MEs. By using BCMA, only one of the three studies demonstrated a significant reduction in medication administration errors, although that was largely attributable to time errors.
      • DeYoung J.L.
      • VanderKooi M.E.
      • Barletta J.F.
      Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit.
      Two studies showed an increase in observed MEs or no difference from the baseline period in the ICU, unlike non-ICUs.
      • Helmons P.J.
      • Wargel L.N.
      • Daniels C.E.
      Effect of bar-code-assisted medication administration on medication administration errors and accuracy in multiple patient care areas.
      ,
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      A possible explanation for this is the complexity of medication use, variations in medication classes, and multiple medication administration techniques in ICUs versus non-ICUs. Several studies reported mixed evidence regarding the effectiveness of BCMA. Some studies found that BCMA significantly reduced MEs.
      • Bonkowski J.
      • Weber R.J.
      • Melucci J.
      • Pesavento T.
      • Henry M.
      • Moffatt-Bruce S.
      Improving medication administration safety in solid organ transplant patients through barcode-assisted medication administration.
      ,
      • Hassink J.J.
      • Essenberg M.D.
      • Roukema J.A.
      • van den Bemt P.M.
      Effect of bar-code-assisted medication administration on medication administration errors.
      By contrast, van der Veen et al.
      • van der Veen W.
      • van den Bemt P.M.L.A.
      • Wouters H.
      • Bates D.W.
      • Twisk J.W.R.
      • de Gier J.J.
      • et al.
      Association between workarounds and medication administration errors in bar-code-assisted medication administration in hospitals.
      concluded that BCMA was associated with more workarounds by nurses owing to the difficulty of using such a system, which caused more medication administration errors. Berdot et al.
      • Berdot S.
      • Boussadi A.
      • Vilfaillot A.
      • Depoisson M.
      • Guihaire C.
      • Durieux P.
      • et al.
      Integration of a commercial barcode-assisted medication dispensing system in a teaching hospital.
      also found that the difficulties associated with integrating BCMA with the electronic medical record system and the repeated issues of interoperability were the main causes for the failure of the BCMA to reduce MEs.
      Concerning the ADS, the study by Chapuis et al.
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      demonstrated that the intervention was effective in reducing preparation errors, but no significant changes were found in selection and administration errors. Similar to BCMA, mixed results were reported. Some studies found that such a system reduced medication selection and preparation errors,
      • Fanning L.
      • Jones N.
      • Manias E.
      Impact of automated dispensing cabinets on medication selection and preparation error rates in an emergency department: a prospective and direct observational before-and-after study.
      as well as medication administration errors.
      • Risør B.W.
      • Lisby M.
      • Sorensen J.
      An automated medication system reduces errors in the medication administration process: results from a Danish hospital study.
      ,
      • Risør B.W.
      • Lisby M.
      • Sørensen J.
      Complex automated medication systems reduce medication administration errors in a Danish acute medical unit.
      Nevertheless, the dispensing system has many advantages in terms of medication distribution, accessibility, and security of medications, but its capacity to reduce MEs is controversial.
      • Fung E.
      • Leung B.
      Do automated dispensing machines improve patient safety?.
      Two reviews concluded that ADSs have limited impact on MEs, as they reduced certain types of errors (e.g. omitted doses), but did not have a significant role in reducing error other types (e.g. administration of wrong doses).
      • Lehnbom E.C.
      • Oliver K.V.
      • Baysari M.T.
      • Westbrook J.I.
      Evidence briefings on interventions to improve medication safety: automated dispensing systems.
      ,
      • Tsao N.W.
      • Lo C.
      • Babich M.
      • Shah K.
      • Bansback N.J.
      Decentralized automated dispensing devices: systematic review of clinical and economic impacts in hospitals.
      Several limitations were identified in the included studies. These include lack of blinding and lack of multiple measurements before and after intervention, which may mask important changes in results. Another limitation is the short period of postintervention assessment, except for that in the study by Seibert et al.
      • Seibert H.H.
      • Maddox R.R.
      • Flynn E.A.
      • Williams C.K.
      Effect of barcode technology with electronic medication administration record on medication accuracy rates.
      The short-term impact measurement cannot predict whether the effect is maintained in the long term. Chapuis et al.’s
      • Chapuis C.
      • Roustit M.
      • Bal G.
      • Schwebel C.
      • Pansu P.
      • David-Tchouda S.
      • et al.
      Automated drug dispensing system reduces medication errors in an intensive care setting.
      findings are limited by sample size. The applicability and generalisability of the results of the reviewed studies are limited because the implementation of BCMA and automated dispensing technologies showed significant variability regarding its effectiveness in reducing MEs, especially in the ICUs. In addition, the implementation of technologies depends largely on the priorities set by the healthcare organisation, in addition to the nurses' attitudes, beliefs, and perceptions towards such systems.
      • Alford K.F.
      Progressive care nurses' attitudes, beliefs, and perceptions of automated medication dispensing cabinet workarounds: a mixed methods study.

      4.1.2 Educational programs for nurses

      Different educational approaches for nurses were found to be effective in reducing medication preparation and medication administration errors. An integrated program was used by three studies, which makes it difficult to ascertain which of the included interventions were the most effective. However, some of the educational components were found to be similar in two studies,
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      ,
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      despite Tan et al.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      focusing on parenteral medications and Nguyen et al.
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      focusing specifically on intravenous medications. There were some specific areas (i.e. the secondary aims of two studies) where no reduction was identified, for example, concentration errors
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      and using inappropriate solvents.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      Postintervention rates remained high in two studies, with 48.9%
      • Nguyen H.T.
      • Pham H.T.
      • Vo D.K.
      • Nguyen T.D.
      • van den Heuvel E.R.
      • Haaijer-Ruskamp F.M.
      • et al.
      The effect of a clinical pharmacist-led training programme on intravenous medication errors: a controlled before and after study.
      and 50%.
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      A possible reason is that the baseline error rate for both studies was higher than that in the other studies. In addition, both studies combined the error rates for both preparation and administration together, unlike other studies that reported the rate for a specific ME type.
      Unlike technology-based interventions, several studies found that a multicomponent educational program aiming to improve nurses’ knowledge on medication processes was effective in reducing ME rates.
      • Abbasinazari M.
      • Zareh-Toranposhti S.
      • Hassani A.
      • Sistanizad M.
      • Azizian H.
      • Panahi Y.
      The effect of information provision on reduction of errors in intravenous drug preparation and administration by nurses in ICU and surgical wards.
      ,
      • Chedoe I.
      • Molendijk H.
      • Hospes W.
      • Van den Heuvel E.R.
      • Taxis K.
      The effect of a multifaceted educational intervention on medication preparation and administration errors in neonatal intensive care.
      A clinical pharmacist-led education program was found to be effective in improving care quality, reducing ME rates, and severity of MEs.
      • Mostafa L.S.
      • Sabri N.A.
      • El-Anwar A.M.
      • Shaheen S.M.
      Evaluation of pharmacist-led educational interventions to reduce medication errors in emergency hospitals: a new insight into patient care.
      ,
      • Mueller S.K.
      • Sponsler K.C.
      • Kripalani S.
      • Schnipper J.L.
      Hospital-based medication reconciliation practices: a systematic review.
      Regarding patients with feeding tubes, this review result is consistent with two studies demonstrating that an integrated program can reduce preparation and administration errors.
      • Lohmann K.
      • Ferber J.
      • Send A.
      • Haefeli W.
      • Seidling H.
      Inappropriate crushing information on ward lists: cytotoxic drugs, capsules, and modified release formulations are gravely neglected.
      ,
      • Nascimento M.M.G.
      • Reis A.M.M.
      • Wick J.Y.
      • Ribeiro A.
      Drug administration through feeding tubes; an integrated qualification program.
      Despite the reported positive effects, several limitations were noted. Firstly, long-term effects were not investigated, as there is a potential risk that nurses would return to preintervention practices over time. Two studies did not achieve the prespecified sample size, decreasing the possibility of scientifically valid outcome.
      • Lohmann K.
      • Gartner D.
      • Kurze R.
      • Schösler T.
      • Schwald M.
      • Störzinger D.
      • et al.
      More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.
      ,
      • Tan S.Y.
      • Said M.M.
      • Rahman R.A.
      • Taha N.A.
      The effect of education intervention on parenteral medication preparation and administration among nurses in a general intensive care unit.
      Moreover, the four studies did not have multiple before and after measurements. Given the methodological limitations, the generalisability of the results is limited.

      4.1.3 Other interventions

      This review found that Simplist prefilled syringes were significantly effective in reducing preparation errors.
      • Burger M.
      • Degnan D.
      Comparative safety, efficiency, and nursing preference among 3 methods for intravenous push medication preparation: a randomized crossover simulation study.
      Similar results were found in a prospective, multisite, and observational study comparing Simplist prefilled syringes with traditional preparation syringes including Carpuject prefilled syringes: the ME rate was 2.5% vs. 10.4%.
      • Hertig J.B.
      • Degnan D.D.
      • Scott C.R.
      • Lenz J.R.
      • Li X.
      • Anderson C.M.
      A comparison of error rates between intravenous push methods: a prospective, multisite, observational study.
      These findings are consistent with a prospective crossover study.
      • Moreira M.E.
      • Hernandez C.
      • Stevens A.D.
      • Jones S.
      • Sande M.
      • Blumen J.R.
      • et al.
      Color-coded prefilled medication syringes decrease time to delivery and dosing error in simulated emergency department pediatric resuscitations.
      However, the primary bias in this study is the lack of blinding nurses, those who delivered the intervention, and the outcome assessor(s). Given this and the fact that prefilled syringes are still more expensive than the traditional vial-and-syringe process,
      • Sacha G.
      • Rogers J.A.
      • Miller R.L.
      Pre-filled syringes: a review of the history, manufacturing and challenges.
      the applicability and generalisability of the results may be compromised.
      With regard to the new protocolised program logic form by Benoit et al.,
      • Benoit E.
      • Eckert P.
      • Theytaz C.
      • Joris-Frasseren M.
      • Faouzi M.
      • Beney J.
      Streamlining the medication process improves safety in the intensive care unit.
      this review indicated that the elimination of the transcription stage and other additional modifications to streamline the communication process among clinicians and nurses in the ICU was effective in reducing nurses’ MEs. One of the strengths of this study is the blinding of nurses because a chart review was used as a data collection method, decreasing the potential risk of bias. Although this detection method is less intrusive than others, it has lower functionality and less accuracy in ME detection than direct observation.
      • Meyer-Massetti C.
      • Cheng C.M.
      • Schwappach D.L.B.
      • Paulsen L.
      • Ide B.
      • Meier C.R.
      • et al.
      Systematic review of medication safety assessment methods.
      This study is the only one that implemented multiple measurements, which increases the rigor of the outcome. Despite the positive findings, one potential limitation is that none of the multiple interventions described was directly correlated with the reported improvements in reducing MEs, which in turn may weaken the validity of inferences. Similarly, the tailored form and multiple components were a barrier to compare results with others. Thus, the generalisability of the study results is limited.
      With respect to PIP by Romero et al.,
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      this review demonstrated equivocal effects, showing inconsistent effectiveness levels on different ME types. Although these strategies reduced half of administration errors, no difference was noted in the preparation errors. Owing to the multiple actions in the interventions and focusing on different errors from different types, the comparison with other studies was found to be more complicated. One of the limitations of Romero et al.′s
      • Romero C.M.
      • Salazar N.
      • Rojas L.
      • Escobar L.
      • Grinen H.
      • Angelica Berasain M.
      • et al.
      Effects of the implementation of a preventive interventions program on the reduction of medication errors in critically ill adult patients.
      study is that none of the four described interventions was directly connected with the reported improvements in reducing MEs; therefore, it is difficult to know what might have made the difference. Other limitations include lack of multiple measurements and the individuals' awareness of the observation. The applicability of such programs is limited and depends largely on the designed components and how the program is going to be rolled out and implemented.
      The findings of this review support the recommendation to plan for the implementation of several interventions through a quality improvement project, as no individual intervention appeared clearly superior to the others. The quality improvement team might consider including the following key components: (i) developing an educational program for nurses focusing on knowledge aspects, attitudes, and behaviours towards MEs and safety and implementing this using simulation-based education (the JBI level of evidence ranges from 2.c to 2.d); (ii) using labelled prefilled syringes for specific medications and under specific conditions (the JBI level of evidence is 1.c); and (iii) the use of an interprofessional protocolised program logic form may be beneficial (the JBI level of evidence is 2.d); however, this requires further confirmatory analyses. This confirmation may be achieved through a gradual implementation plan for the project, commencing each intervention within a specific time frame and sequentially, until all interventions are active and running. It is recommended to start with nurses’ education because this could also include an introduction of the other planned interventions. A key aspect of this project would be to commit to rigorous investigation of the effectiveness of each intervention throughout implementation and to ensure that valid and reliable measures are used.

      4.2 Limitations

      The development and adherence to a priori protocol reduced the risk of bias; a limitation was that the protocol and title were not able to be registered. The external validity of the study was further limited by the exclusion of studies published in a language other than English. This may have reduced the likelihood of retrieving studies conducted in countries where English is not a common language, thus reducing the ability to generalise the findings to non-English speaking populations. This illustrates a potential gap in the research and provides a future research opportunity.

      5. Conclusion

      In this systematic review, we investigated the effect of interventions to decrease the rates of nurses' MEs in adult ICUs. Of the 11 included experimental and quasi-experimental studies, the evidence for effective interventions was limited. Prefilled syringes, nurses' education programs, and the protocolised program logic form were most effective in reducing MEs; however, the included studies in this review were susceptible to potential risk of bias. Future rigorous research is needed to explore the effectiveness of multicomponent interventions in terms of correlating a single component to reducing specific types of MEs. While this review included different interventions that targeted some potential risk factors of MEs (e.g. nurses’ knowledge and skills), other important interventions that target other factors were either not found or excluded as they did not meet the inclusion criteria. These include interventions that may contribute to reducing the risk of MEs such as addressing workloads, shift patterns, and interruptions or distractions. Therefore, further studies using more rigorous designs such as RCTs focusing on these areas are highly recommended, as they can make comparison between groups and provide robust evidence.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Conflict of interest

      None.

      CRediT authorship contribution statement

      Zamzam Mohanna: conception, design, analysis, and interpretation of data, and drafting the article, critically revised this article, approved this version, accountable for all aspects of the work's integrity and accuracy; Snezana Kusljic: conception, design, analysis, and interpretation of data, and drafting the article, critically revised this article, approved this version, accountable for all aspects of the work's integrity and accuracy; Rebecca Jarden: conception, design, analysis, and interpretation of data, and drafting the article, critically revised this article, approved this version, accountable for all aspects of the work's integrity and accuracy
      All authors have approved this version and agree to be accountable for all aspects of the work's integrity and accuracy.

      Appendix A. Supplementary data

      The following is the Supplementary data to this article:

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