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Nursing interventions to reduce medication errors in paediatrics and neonates: Systematic review and meta-analysis

Published:September 07, 2021DOI:https://doi.org/10.1016/j.pedn.2021.08.024

      Highlights

      • Medication errors are multifacceted requring complex intervetion.
      • Causes of errors need to be identified prior implementation of appropriate intervetions.
      • Medication safety education is an integral element of interventions in a bid to reduce administration errors.
      • Interdisciplinary collaboration in the medication process contributes to the reduction of medication administration errors

      Abstract

      Background

      Medication errors are a great concern to health care organisations as they are costly and pose a significant risk to patients. Children are three times more likely to be affected by medication errors than adults with medication administration error rates reported to be over 70%.

      Objective

      To identify nursing interventions to reduce medication administration errors and perform a meta-analysis.

      Methods

      Online databases; British Nursing Index (BNI), Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE and MEDLINE were searched for relevant studies published between January 2000 to 2020. Studies with clear primary or secondary aims focusing on interventions to reduce medication administration errors in paediatrics, children and or neonates were included in the review.

      Results

      442 studies were screened and18 studies met the inclusion criteria. Seven interventions were identified from included studies; education programmes, medication information services, clinical pharmacist involvement, double checking, barriers to reduce interruptions during drug calculation and preparation, implementation of smart pumps and improvement strategies. Educational interventional aspects were the most common identified in 13 out of 18 included studies. Meta-analysis demonstrated an associated 64% reduction in medicine administration errors post intervention (pooled OR 0.36 (95% Confidence Interval (CI) 0.21–0.63) P = 0.0003).

      Conclusion

      Medication safety education is an important element of interventions to reduce administration errors. Medication errors are multifaceted that require a bundle interventional approach to address the complexities and dynamics relevant to the local context. It is imperative that causes of errors need to be identified prior to implementation of appropriate interventions.

      Keywords

      Introduction

      Medication errors, be it prescribing, preparation and dispensing, administration or monitoring are key patient safety concerns and a quality measure of healthcare medication process management. When they occur, medication errors produce a variety of problems for patients, ranging from minor discomfort to substantial morbidity that may lead to increased length of hospital stay or death under certain circumstances (
      • Stucky E.R.
      Prevention of medication errors in the pediatric inpatient setting.
      ). An estimated 18.7% - 56% of all adverse events among hospitalised patients result from preventable medication errors (
      • von Laue N.C.
      • Schwappach D.L.
      • Koeck C.M.
      The epidemiology of preventable adverse drug events: A review of the literature.
      ), however even more significant to realise is that medication errors can occur in the absence of injury to the patient. The National Coordinating Council for Medication Error Reporting and Prevention (
      • National Coordinating Council for Medication Error Reporting an Prevention (NCC MERP)
      About medication errors.
      ) described medication errors as ‘any preventable event that may cause or lead inappropriate medication use or patient harm while medication is in the control of healthcare professional, patient or consumer’, demonstrating that medication errors occur as a result of human mistakes or system flaws (
      • Stucky E.R.
      Prevention of medication errors in the pediatric inpatient setting.
      ). For these reasons and more, in 2017 the World Health Organisation launched a global initiative aiming at reducing medication errors by 50% within a 5 year time span (
      • Bonner L.
      WHO initiative to focus on reducing medication errors by 50% in 5 years.
      ).
      The paediatric and neonatal patient population are three times more likely to be affected by medication errors than adults (
      • Kaushal R.
      • Bates D.W.
      • Landrigan C.
      • McKenna K.J.
      • Clapp M.D.
      • Federico F.
      • Goldmann D.A.
      Medication errors and adverse drug events in pediatric inpatients.
      ;
      • Simpson J.H.
      • Lynch R.
      • Grant J.
      • Alroomi L.
      Reducing medication errors in the neonatal intensive care unit.
      ), and significantly higher error rates have been reported during prescribing and administration in comparison to dispensing and monitoring (
      • Kaushal R.
      • Bates D.W.
      • Landrigan C.
      • McKenna K.J.
      • Clapp M.D.
      • Federico F.
      • Goldmann D.A.
      Medication errors and adverse drug events in pediatric inpatients.
      ;
      • Krähenbühl-Melcher A.
      • Schlienger R.
      • Lampert M.
      • Haschke M.
      • Drewe J.
      • Krähenbühl S.
      Drug-related problems in hospitals: A review of the recent literature.
      ;
      • Ross L.M.
      • Wallace J.
      • Paton J.Y.
      Medication errors in a paediatric teaching hospital in the UK: Five years operational experience.
      ). Medication prescribing and administration error rates have been reported in various studies ranging from 3 to 37% and 72–78% respectively (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ;

      Elliott, R., Camacho, E., Campbell, F., Jankovic, D., Martyn St James, M., Kaltenthaler, E., et al (2018). Prevalence and Economic Burden of Medication Errors in The NHS in England. Rapid evidence synthesis and economic analysis of the prevalence and burden of medication error in the UK. Policy Research Unit in Economic Evaluation of Health and Care Interventions 2018. Universities of Sheffield and York. Available online at: http://www.eepru.org.uk/article/prevalence-and-economic-burden-of-medication-errors-in-the-nhs-in-england/ (Accessed on 12 May 2021).

      ).
      Implementation of drug therapy in children and infants can be complex due to one or more of the following; (i) treatment of rare and life-threatening conditions requiring continuous adjustment of dosing and drug therapy, (ii) narrow therapeutic range of some drugs, and (iii) individualised dosing based on factors such as age, weight, renal functions and maturation of enzyme systems (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ;
      • Niemann D.
      • Bertsche A.
      • Meyrath D.
      • Oelsner S.
      • Ewen A.L.
      • Pickardt B.
      • Bertsche T.
      Drug handling in a paediatric intensive care unit--can errors be prevented by a three-step intervention?.
      ). Literature highlights that children are at greater risk of harm than adults when medication errors occur (
      • 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.
      ;
      • Lindell-Osuagwu L.
      • Korhonen M.J.
      • Saano S.
      • Helin-Tanninen M.
      • Naaranlahti T.
      • Kokki H.
      Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature.
      ).
      Due to the nature of errors, many studies have looked broadly at interventions that looked at reducing errors across all healthcare professionals' practice. There is a place for such interventions; however nurses are at the forefront of medication administration where errors are highest (reported to range from 72 to 78%) (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ;

      Elliott, R., Camacho, E., Campbell, F., Jankovic, D., Martyn St James, M., Kaltenthaler, E., et al (2018). Prevalence and Economic Burden of Medication Errors in The NHS in England. Rapid evidence synthesis and economic analysis of the prevalence and burden of medication error in the UK. Policy Research Unit in Economic Evaluation of Health and Care Interventions 2018. Universities of Sheffield and York. Available online at: http://www.eepru.org.uk/article/prevalence-and-economic-burden-of-medication-errors-in-the-nhs-in-england/ (Accessed on 12 May 2021).

      ), and it has been realised that administration errors are the hardest to intercept causing direct harmful consequences for patients (
      • Buckley M.S.
      • Erstad B.L.
      • Kopp B.J.
      • Theodorou A.A.
      • Priestley G.
      Direct observation approach for detecting medication errors and adverse drug events in a pediatric intensive care unit.
      ). Therefore the purpose of this review was to comprehensively compile specific nursing interventions to reduce drug administration errors and where applicable outline size of effect.

      Methods

      Data sources

      Five electronic databases were searched; British Nursing Index (BNI), Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE and MEDLINE. To maximise search sensitivity, a combination of various free text key words and Medical Subject Headings (MeSH terms) were used. Search terms included; paediatric, neonates, infants, babies, medication, drug, error. Databases were searched from January 2000 to February 2020.

      Study selection

      The review considered peer reviewed published studies involved in implementation of an intervention aimed at reducing medication administration errors among nurses in in-patient paediatric clinical settings. Children were defined as individuals between 0 and 18 years of age. Papers published in other languages were considered if an English translation was available. Excluded studies included case studies, epidemiological studies, reviews, editorials and opinion papers.
      Search strategy was performed by the hospital librarian with extensive experience in literature searches. Two authors independently identified studies at abstract and full text stages. Disagreements on potential studies for inclusion were resolved by discussion to reach consensus or involvement of the third author.

      Data extraction

      Data extraction was performed independently by two authors using a pre-piloted standardised form. The form sections included; author and date of publication, study design, country of study, clinical setting type, sample size, intervention implemented, pre and post- intervention outcomes.

      Methodology quality assessment

      The quality Assessment Tool for Before and After (Pre-Post) studies with No Control Group (BAQA) was used to assess the risk of bias of included studies (). This was calculated independently by two authors, any inconsistencies in scoring of items were resolved through consensus.

      Statistical analysis

      Most included studies presented the results in percentages and error rates. Using pre and post intervention total drug administration error numbers, odds ratios (OR) and 95% confidence intervals (95% CI) for the likelihood of medication error reduction after the intervention (exposure) was calculated. A meta-analysis was performed in Rev. Man5 (
      • Higgins J.
      • Green S.
      Cochrane Handbook for Systematic Reviews of Interventions Version 6.0. The Cochrane Collaboration 2019.
      ) using the random effect method for a pooled size effect of implementing any error reduction intervention. For the studies where OR could not be calculated, a qualitative synthesis is given.

      Results

      Search process

      Online searches identified 512 studies. After removal of duplicates 442 articles were screened at title and abstract stages. Nineteen studies were assessed at full-text and 18 studies met the inclusion criteria and were included for data extraction (Table 1 Characteristics of included studies). Fig. 1 provides an overview of the search process.
      Table 1Characteristics of included studies.
      Author and yearCountryType of studyParticipantsSample size (N)InterventionsResults
      • Yamamoto L.
      • Kanemori J.
      Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration.
      USAProspective cohortNurses (Paediatric Emergency Department)38computer-assisted vs conventional paediatric drug dosing and administrationMean conventional drug administration and dosing time 1243s vs mean computer program total time of 879 s (P < 0.001), Mean error 1.8 conventional method vs 0.7 computer programme (P < 0.001). OR 0.55 95% CI (0.35–0.86)
      Highlihgt OR calculated from baseline data presented in the respective study.
      .
      • Hebbar K.B.
      • Colman N.
      • Williams L.
      • Pina J.
      • Davis L.
      • Bost J.E.
      • Frank G.
      A quality initiative: A system-wide reduction in serious medication events through targeted simulation training.
      USAProspective cohortChildren's Hospital Nurses (general care units, emergency departments, and intensive care units)1434simulation training program implementing MAE bundle (The Five Rights, Med-Zone, and Independent Double Check)Serious MAEs rates decreased from 2.5 events per month during the 12-month pre-intervention period to 1.4 events per month during the 20-month intervention rollout (RR = 1.78, 95% CI = 1.03–3.1, P = 0.029). MAEs further decreased to 0.86 events per month during the 7-month post-intervention period (RR = 2.9, 95% CI = 1.2–8.5, P = 0.014) (63% decrease in MAEs from the baseline period, with a 45% drop in higher classified errors).
      • Colligan L.
      • Guerlain S.
      • Steck S.E.
      • Hoke T.R.
      Designing for distractions: A human factors approach to decreasing interruptions at a centralised medication station.
      USAProspective observationalPaediatric Specialty(nurses)Single ward (20 nurses)Barriers to reduce interruptions during drug calculation and preparationFrequency of interruption: mean interruption rate per minute of occurrence was significantly reduced from 1.4 pre-intervention to 0.27 post-intervention (paired t-test = 5.7, df = 98, p < 0.01). The length of time spent from beginning to end of each occurrence was not significantly reduced (120 s vs 117 s pre-intervention and post-intervention, respectively).
      • McSweeney J.
      • Rosenholm E.
      • Penny K.
      • Mullen M.P.
      • Kulik T.J.
      Improving safety of intravenous prostacyclin administration to pediatric patients with pulmonary hypertension.
      USAProspective cohortPaediatric Specialty (nurses)19 errors were analysed and deemed preventable by the SERS reporterimprovement strategy included several initiative(policy change, change of process, education programme, and hospital-wide safety initiatives)The number of therapy errors per 1000 patient days fell from 19.28 in 2009 to 5.95 in 2016 (The CIPT error rate decreased by 69% from 2009 to 2016). Chi2 analysis was used to compare the result for 2009 with that for each subsequent year, with P values of 0.66, 0.35, 0.16, 0.09, 0.03, 0.12, and 0.25 found for 2010 through 2016, respectively.
      • Subramanyam R.
      • Mahmoud M.
      • Buck D.
      • Varughese A.
      Infusion medication error reduction by two-person verification: A quality improvement initiative.
      USAProspective studyChildren's Hospital (anaesthetists and nurses)1292-person verification system for infusion pump programming before medication administrationDuring the intervention 4 errors were rectified before the medication was administered to the patient. There was no delay in case starts (>90% before and during the project).The rate of 2-person verification of infusion pump programming increased from 0% to 90% and was sustained.
      • Kanjia M.K.
      • Adler A.C.
      • Buck D.
      • Varughese A.M.
      Increasing compliance of safe medication administration in pediatric anesthesia by use of a standardized checklist.
      USAProspective cohortPaediatric anaesthesia (anaesthetists, physicians and nurses)633 checklists and electronic medical recordsEducation and Checklist toolThe percentage of compliance with the safe administration checklist for acetaminophen in the preoperative period increased to 97%. Use of the paper checklist likely prompted the appropriate increase in compliance with safe administration. Additionally, provider-specific feedback produced a significant increase in compliance with use of the checklist.
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      SpainProspective cohortNICU (doctors, nurses, nurses' aids and pharmacists)94Education strategyPost-intervention prescription error rate and the percentage of registers with one or more incident decreased significantly from 20.7 to 3% (p < 0.001) and from 19.2 to 2.9% (p < 0.001), respectively. OR 0.12 95% CI (0.09–0.16)
      Highlihgt OR calculated from baseline data presented in the respective study.
      • Manrique-Rodríguez S.
      • Sánchez-Galindo A.C.
      • López-Herce J.
      • Calleja-Hernández M.
      • Martínez-Martínez F.
      • Iglesias-Peinado I.
      • Fernández-Llamazares C.M.
      Impact of implementing smart infusion pumps in a pediatric intensive care unit.
      SpainProspective observational interventionalPICU (nurses)97 alarms associated with real programming errorsimplementing smart infusion pumps92 programming errors with potentially harm to the patient were intercepted (84% of errors involved analgesics, anti-infectives, inotropes, and sedatives, 97% of the errors resulted from user programming of doses or infusion rates above the hard limits defined in the smart pump drug library, potential consequences of the intercepted errors were considered to be of moderate, serious, or catastrophic severity in 49% of cases.
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      SpainProspective observational studyNICU (doctors, nurses and pharmacists)10 Spanish neonatal intensive care units and one hospital pharmacy service participated in the studyeducational and protocol standardisation programmeIn NICU, 1.35% of samples registered calculation errors in pre-intervention phase; no calculation errors were registered in hospital pharmacy service (HPS) samples. In post-intervention phase, no calculation errors were registered in either group. Accuracy error rate decreased both in NICU (54.7vs 23% P < 0.001 Chi2) and HPS (38.3 vs 14.6% P < 0.010 Chi2). OR 0.38 95% CI (0.28–0.53)
      Highlihgt OR calculated from baseline data presented in the respective study.
      • Niemann D.
      • Bertsche A.
      • Meyrath D.
      • Oelsner S.
      • Ewen A.L.
      • Pickardt B.
      • Bertsche T.
      Drug handling in a paediatric intensive care unit--can errors be prevented by a three-step intervention?.
      GermanyProspective intervention studyPCCU (nurses)1 PCCU Unit (142 participants)3 step intervention (training course, information handout, and a 76-page reference book)Drug error prevalence decreased from 83% (555 errors/668 processes) to 63% (554/883; p < 0.001) after the intervention, OR 0.76 95% CI (0.65–0.88)
      Highlihgt OR calculated from baseline data presented in the respective study.
      .Number of affected patients remained unchanged (95% vs. 89%, p = 0.370). PO drugs (1.33 errors/ process) were more error-prone than IV drugs (0.64), despite being used less frequently (27% vs. 73% of all processes, p < 0.001). The interventions decreased the prevalence to 0.77 errors/process (p < 0.001) in PO and to 0.52 in IV drugs (p = 0.025). O
      • Bertsche T.
      • Bertsche A.
      • Krieg E.M.
      • Kunz N.
      • Bergmann K.
      • Hanke G.
      • Haefeli W.E.
      Prospective pilot intervention study to prevent medication errors in drugs administered to children by mouth or gastric tube: A programme for nurses, physicians and parents.
      GermanyProspective,

      two-period cohort intervention
      Paediatric neurology ward (doctors, nurses and parents)17 nurses and 30 parentseducational program including; implementation instructions for appropriate drug administration, and drug information servicesPost-intervention errors reduced from 261/646 tasks (40.4%) to 36/453 (7.9%, p < 0.001) in nurses and from 28/29 (96.6%) to 2/36 (5.6%, p < 0.001) in parents. OR 0.11, 955 CI (0.07–0.16)
      Highlihgt OR calculated from baseline data presented in the respective study.
      • Otero P.
      • Leyton A.
      • Mariani G.
      • Ceriani Cernadas J.M.
      Medication errors in pediatric inpatients: Prevalence and results of a prevention program.
      ArgentinaCross-sectionalPaediatrics hospital (physicians, nurses and pharmacists)4496 medicationseducational program including; a) proposed modifications on medication prescription process (2) active interaction with pharmacists during rounds, and (3) implementation of a 10 steps check list on medication error reduction.Prevalence of medication error rate reduced from 11.4% pre-intervention to 7.3% post-intervention (ARR (−4.1%), 95% CI (−2.3) - (−5.8)), OR (0.61, 95% CI 0.50–0.75).

      Prescription error rate decreased from 11.4% to 7.3%, ARR ((−8.1%), 95% CI (−4.6) - (−11.6)), OR (0.48, 95% CI, 0.36–0.65).

      Administration error rate decreased from 17.3% to 9.2% ARR ((−2.5%), 95% CI (−0.5) - (−4.5)), OR (0.68, 95% CI, 0.51–0.91).
      • Guérin A.
      • Tourel J.
      • Delage E.
      • Duval S.
      • David M.-J.
      • Lebel D.
      • Bussières J.-F.
      Accidents and incidents related to intravenous drug administration: A pre–post study following implementation of smart pumps in a teaching hospital.
      CanadaRetrospective pre–postPaediatric hospital (nurses, doctors and pharmacists)All staff in a 500 bed mother-child hospitalimplementing smart infusion pumpsA total of 2911 (accidents and incidents) events related to medications, devices, and equipment were self-reported by clinical staff in the pre-phase (Y0), 3523 in the post-phase (Y1), and 2788 in the post-phase (Y2). The total AIIV increased from 1432 in Y0 to 1834 in Y1 and further decreased to 1389. Drug related events OR post phase (Y2) 0.81, 95% CI (0.67–1.0)
      Highlihgt OR calculated from baseline data presented in the respective study.
      • Raja Lope R.J.
      • Boo N.Y.
      • Rohana J.
      • Cheah F.C.
      A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.
      MalaysiaProspective pre and post intervention studyNICU (nurses)50 nurses observed during phase 1

      51 nurses observed during phase 2
      Education programmeMAEs reduced from 31% (59/88) pre intervention to 15.4% (26/169) post-intervention (P < 0.001) OR 0.40, 95% CI (0.24–0.67)
      Highlihgt OR calculated from baseline data presented in the respective study.
      • Stewart M.
      • Purdy J.
      • Kennedy N.
      • Burns A.
      An interprofessional approach to improving paediatric medication safety.
      Northern IrelandProspective cohortFourth year medical students and third year nursing students193education programme (teaching and workshop training)After intervention, students reported an increase in their knowledge and awareness on paediatric medication safety, pre and post mean scores 53.9 vs 69.8 (mean difference 15.9, 95% CI 10.4–21.4 p < 0.001), shared learning pre and post mean scores 67.9 vs 76.6 (mean difference 8.9, 95% CI 4.3–13.1 p < 0.001)
      • 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.
      NetherlandsProspective cohortNICU nurses311/718 (43%) doses observed pre-intervention, 284/1221 (23%) doses observed post-interventionMultifaceted educational programmeThe incidence of errors decreased from 49% to 31%. Pre-intervention rates 0.3% severe errors, 26% moderate and 23% minor errors. Post-intervention rates 0% severe errors, 23% moderate and 8% minor errors. OR 0.49 (0.29–0.84) for period (p = 0.032), route of administration (p = 0.001)
      • Simpson J.H.
      • Lynch R.
      • Grant J.
      • Alroomi L.
      Reducing medication errors in the neonatal intensive care unit.
      Scotland, UKProspective cohortNICU(doctors and nurse)105 drug errorsEducational program including; implementation of clinical pharmacy, and drug information services.Post-interventions, monthly medication errors fell from a mean (SD) of 24.1 (1.7) per 1000 neonatal activity days to 5.1 (3.6) per 1000 days (p < 0.001) in the following three months. The subsequent change over of junior medical staff was associated with a significant increase in medication errors to 12.2 (3.6) per 1000 neonatal activity days (p = 0.037).
      • Abuelsoud N.
      Pharmacy quality improvement project to enhance the medication management process in pediatric patients.
      Saudi ArabiaProspective cohortPaediatric specialty (physicians, nurses and pharmacists)900 medical files reviewed to detect drug related problemseducational program including; implementation of clinical pharmacy, and drug information servicesMAE rates during prescribing, administration, and monitoring stages decreased from 47, 60, and 56% to 10, 10 and 15% respectively within 9 months after intervention. OR 0.15, 95% ci (0.13–0.17)
      Highlihgt OR calculated from baseline data presented in the respective study.
      , prescription error OR 0.13, 95% CI (0.08–0.16)
      Highlihgt OR calculated from baseline data presented in the respective study.
      , administration error OR 0.12, 95% (0.09–0.15)
      Highlihgt OR calculated from baseline data presented in the respective study.
      .
      Abbreviations: PCCU, Paediatric Critical Care Unit, ARR, absolute rate ratio, OR, odds ratio, RR, rate ratio, MAEs, medical administration errors.
      low asterisk Highlihgt OR calculated from baseline data presented in the respective study.
      Fig. 1
      Fig. 1Flow diagram of included and excluded studies.
      Studies were conducted in seven countries. The majority of studies (six) were from the USA (
      • Colligan L.
      • Guerlain S.
      • Steck S.E.
      • Hoke T.R.
      Designing for distractions: A human factors approach to decreasing interruptions at a centralised medication station.
      ;
      • Hebbar K.B.
      • Colman N.
      • Williams L.
      • Pina J.
      • Davis L.
      • Bost J.E.
      • Frank G.
      A quality initiative: A system-wide reduction in serious medication events through targeted simulation training.
      ;
      • Kanjia M.K.
      • Adler A.C.
      • Buck D.
      • Varughese A.M.
      Increasing compliance of safe medication administration in pediatric anesthesia by use of a standardized checklist.
      ;
      • McSweeney J.
      • Rosenholm E.
      • Penny K.
      • Mullen M.P.
      • Kulik T.J.
      Improving safety of intravenous prostacyclin administration to pediatric patients with pulmonary hypertension.
      ;
      • Subramanyam R.
      • Mahmoud M.
      • Buck D.
      • Varughese A.
      Infusion medication error reduction by two-person verification: A quality improvement initiative.
      ;
      • Yamamoto L.
      • Kanemori J.
      Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration.
      ), three from Spain (
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      ;
      • Campino A.
      • Santesteban E.
      • Pascual P.
      • Sordo B.
      • Arranz C.
      • Unceta M.
      • Lopez-de-Heredia I.
      Strategies implementation to reduce medicine preparation error rate in neonatal intensive care units.
      ;
      • Manrique-Rodríguez S.
      • Sánchez-Galindo A.C.
      • López-Herce J.
      • Calleja-Hernández M.
      • Martínez-Martínez F.
      • Iglesias-Peinado I.
      • Fernández-Llamazares C.M.
      Impact of implementing smart infusion pumps in a pediatric intensive care unit.
      ), two from Germany (
      • Bertsche T.
      • Bertsche A.
      • Krieg E.M.
      • Kunz N.
      • Bergmann K.
      • Hanke G.
      • Haefeli W.E.
      Prospective pilot intervention study to prevent medication errors in drugs administered to children by mouth or gastric tube: A programme for nurses, physicians and parents.
      ;
      • Niemann D.
      • Bertsche A.
      • Meyrath D.
      • Oelsner S.
      • Ewen A.L.
      • Pickardt B.
      • Bertsche T.
      Drug handling in a paediatric intensive care unit--can errors be prevented by a three-step intervention?.
      ) and one from each of the following nations; Argentina, Canada, Malaysia, Netherlands, Northern Ireland, Scotland (UK) and Saudi Arabia;(
      • Abuelsoud N.
      Pharmacy quality improvement project to enhance the medication management process in pediatric patients.
      ;
      • 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.
      ;
      • Guérin A.
      • Tourel J.
      • Delage E.
      • Duval S.
      • David M.-J.
      • Lebel D.
      • Bussières J.-F.
      Accidents and incidents related to intravenous drug administration: A pre–post study following implementation of smart pumps in a teaching hospital.
      ;
      • Otero P.
      • Leyton A.
      • Mariani G.
      • Ceriani Cernadas J.M.
      Medication errors in pediatric inpatients: Prevalence and results of a prevention program.
      ;
      • Raja Lope R.J.
      • Boo N.Y.
      • Rohana J.
      • Cheah F.C.
      A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.
      ;
      • Simpson J.H.
      • Lynch R.
      • Grant J.
      • Alroomi L.
      Reducing medication errors in the neonatal intensive care unit.
      ;
      • Stewart M.
      • Purdy J.
      • Kennedy N.
      • Burns A.
      An interprofessional approach to improving paediatric medication safety.
      ).

      Methodology quality assessment

      All included studies in this paper clearly stated study objectives, study population and the interventions. All studies were before and after intervention studies. Sixteen studies were prospective cohort studies and one was a retrospective cohort (
      • Guérin A.
      • Tourel J.
      • Delage E.
      • Duval S.
      • David M.-J.
      • Lebel D.
      • Bussières J.-F.
      Accidents and incidents related to intravenous drug administration: A pre–post study following implementation of smart pumps in a teaching hospital.
      ) and another cross-sectional (
      • Otero P.
      • Leyton A.
      • Mariani G.
      • Ceriani Cernadas J.M.
      Medication errors in pediatric inpatients: Prevalence and results of a prevention program.
      ). Two studies (
      • Colligan L.
      • Guerlain S.
      • Steck S.E.
      • Hoke T.R.
      Designing for distractions: A human factors approach to decreasing interruptions at a centralised medication station.
      ;
      • Stewart M.
      • Purdy J.
      • Kennedy N.
      • Burns A.
      An interprofessional approach to improving paediatric medication safety.
      ) rated moderate on risk of bias (25–75%) while the rest rated low risk of bias. Randomisation and blinding of the assessors was not possible due to the nature of the studies.

      Outcomes

      The studies looked at implementation of interventions to reduce medication administration errors (MAEs) in specific individual paediatric clinical areas or across the children's hospital as a whole. Six studies were conducted in all specialties across children's hospitals (
      • Colligan L.
      • Guerlain S.
      • Steck S.E.
      • Hoke T.R.
      Designing for distractions: A human factors approach to decreasing interruptions at a centralised medication station.
      ;
      • Guérin A.
      • Tourel J.
      • Delage E.
      • Duval S.
      • David M.-J.
      • Lebel D.
      • Bussières J.-F.
      Accidents and incidents related to intravenous drug administration: A pre–post study following implementation of smart pumps in a teaching hospital.
      ;
      • Hebbar K.B.
      • Colman N.
      • Williams L.
      • Pina J.
      • Davis L.
      • Bost J.E.
      • Frank G.
      A quality initiative: A system-wide reduction in serious medication events through targeted simulation training.
      ;
      • McSweeney J.
      • Rosenholm E.
      • Penny K.
      • Mullen M.P.
      • Kulik T.J.
      Improving safety of intravenous prostacyclin administration to pediatric patients with pulmonary hypertension.
      ;
      • Otero P.
      • Leyton A.
      • Mariani G.
      • Ceriani Cernadas J.M.
      Medication errors in pediatric inpatients: Prevalence and results of a prevention program.
      ), seven in NICU or PCCU only (
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      ;
      • Campino A.
      • Santesteban E.
      • Pascual P.
      • Sordo B.
      • Arranz C.
      • Unceta M.
      • Lopez-de-Heredia I.
      Strategies implementation to reduce medicine preparation error rate in neonatal intensive care units.
      ;
      • 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.
      ;
      • Manrique-Rodríguez S.
      • Sánchez-Galindo A.C.
      • López-Herce J.
      • Calleja-Hernández M.
      • Martínez-Martínez F.
      • Iglesias-Peinado I.
      • Fernández-Llamazares C.M.
      Impact of implementing smart infusion pumps in a pediatric intensive care unit.
      ;
      • Niemann D.
      • Bertsche A.
      • Meyrath D.
      • Oelsner S.
      • Ewen A.L.
      • Pickardt B.
      • Bertsche T.
      Drug handling in a paediatric intensive care unit--can errors be prevented by a three-step intervention?.
      ;
      • Raja Lope R.J.
      • Boo N.Y.
      • Rohana J.
      • Cheah F.C.
      A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.
      ), two in paediatric theatres (
      • Kanjia M.K.
      • Adler A.C.
      • Buck D.
      • Varughese A.M.
      Increasing compliance of safe medication administration in pediatric anesthesia by use of a standardized checklist.
      ;
      • Subramanyam R.
      • Mahmoud M.
      • Buck D.
      • Varughese A.
      Infusion medication error reduction by two-person verification: A quality improvement initiative.
      ) and one in an emergency department (
      • Yamamoto L.
      • Kanemori J.
      Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration.
      ) and one in a paediatric neurological ward (
      • Bertsche T.
      • Bertsche A.
      • Krieg E.M.
      • Kunz N.
      • Bergmann K.
      • Hanke G.
      • Haefeli W.E.
      Prospective pilot intervention study to prevent medication errors in drugs administered to children by mouth or gastric tube: A programme for nurses, physicians and parents.
      ). One that looked at interprofessional approach to improving paediatric medication safety through interprofessional workshops to facilitate learning of knowledge was conducted on fourth year medical students and third year nursing students (
      • Stewart M.
      • Purdy J.
      • Kennedy N.
      • Burns A.
      An interprofessional approach to improving paediatric medication safety.
      ).

      Interventions

      Seven individual interventions were identified from the included studies (Appendix 1 Table 1 Summary of Interventions). These included; education programs, drug information services (posters, reference books), involvement of clinical pharmacists, double checking, smart pumps, barriers to reduce interruptions during drug calculation and preparation and improvement strategies (checklists, policy and process change).
      Some of the studies implemented single interventions only while others used a bundle of interventions. Education program interventions were the most common, observed in thirteen studies. Five studies implemented the specific education programs only (
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      ;
      • Campino A.
      • Santesteban E.
      • Pascual P.
      • Sordo B.
      • Arranz C.
      • Unceta M.
      • Lopez-de-Heredia I.
      Strategies implementation to reduce medicine preparation error rate in neonatal intensive care units.
      ; I.
      • 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.
      ;
      • Raja Lope R.J.
      • Boo N.Y.
      • Rohana J.
      • Cheah F.C.
      A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.
      ;
      • Stewart M.
      • Purdy J.
      • Kennedy N.
      • Burns A.
      An interprofessional approach to improving paediatric medication safety.
      ), while the other eight studies included other interventions with education program (
      • Abuelsoud N.
      Pharmacy quality improvement project to enhance the medication management process in pediatric patients.
      ;
      • Bertsche T.
      • Bertsche A.
      • Krieg E.M.
      • Kunz N.
      • Bergmann K.
      • Hanke G.
      • Haefeli W.E.
      Prospective pilot intervention study to prevent medication errors in drugs administered to children by mouth or gastric tube: A programme for nurses, physicians and parents.
      ;
      • Hebbar K.B.
      • Colman N.
      • Williams L.
      • Pina J.
      • Davis L.
      • Bost J.E.
      • Frank G.
      A quality initiative: A system-wide reduction in serious medication events through targeted simulation training.
      ;
      • Kanjia M.K.
      • Adler A.C.
      • Buck D.
      • Varughese A.M.
      Increasing compliance of safe medication administration in pediatric anesthesia by use of a standardized checklist.
      ;
      • McSweeney J.
      • Rosenholm E.
      • Penny K.
      • Mullen M.P.
      • Kulik T.J.
      Improving safety of intravenous prostacyclin administration to pediatric patients with pulmonary hypertension.
      ;
      • Niemann D.
      • Bertsche A.
      • Meyrath D.
      • Oelsner S.
      • Ewen A.L.
      • Pickardt B.
      • Bertsche T.
      Drug handling in a paediatric intensive care unit--can errors be prevented by a three-step intervention?.
      ;
      • Otero P.
      • Leyton A.
      • Mariani G.
      • Ceriani Cernadas J.M.
      Medication errors in pediatric inpatients: Prevalence and results of a prevention program.
      ;
      • Simpson J.H.
      • Lynch R.
      • Grant J.
      • Alroomi L.
      Reducing medication errors in the neonatal intensive care unit.
      ).
      The following three intervention; education, drug information services and clinical pharmacy involvement programmes are closely associated and in some context interdependent, depending on the delivery strategy. Education intervention sessions were delivered periodically through lectures, workshops with scenarios, drug administration simulations and specific practical training for staff involved in intravenous administration. Staff competency was assessed via a series of practical exercises including dose calculations. Staff education materials or medicines information were printed and made available (training course information, handouts, and information providing clear medication administration instruction and good administration practices). Simulations and workshop practicals consisted of high reliability principles consistent with error prevention such as closed loop communication, team member check in and STAR (Stop, Think, Act, Review) (
      • Hebbar K.B.
      • Colman N.
      • Williams L.
      • Pina J.
      • Davis L.
      • Bost J.E.
      • Frank G.
      A quality initiative: A system-wide reduction in serious medication events through targeted simulation training.
      ), and double checking. An example of a simulation exercise is as follows; the staff nurse reads the drug chart, identifies the correct drug from storage, correct dose calculation counter checked by a colleague, prepares medication aseptically, labels prepared drug, check patient's identification, check drug prescription/medication label again, administer medication to the patient ensuring the right time, rate, route, colleague counterchecks administration (
      • Raja Lope R.J.
      • Boo N.Y.
      • Rohana J.
      • Cheah F.C.
      A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.
      ). Sessions were delivered by various staff groups with additional support from pharmacy staff until competency is achieved.
      Clinical pharmacy service interventions were not limited to education only. Clinical pharmacist led daily bedside medications reviews focusing on issues relating to prescribing, documentation and administration were implemented (
      • Simpson J.H.
      • Lynch R.
      • Grant J.
      • Alroomi L.
      Reducing medication errors in the neonatal intensive care unit.
      ). Senior pharmacists were included in the daily medical team ward rounds with specific intravenous medications mixtures prepared in pharmacy (
      • Abuelsoud N.
      Pharmacy quality improvement project to enhance the medication management process in pediatric patients.
      ).
      The use of smart pumps were evaluated in three studies (
      • Guérin A.
      • Tourel J.
      • Delage E.
      • Duval S.
      • David M.-J.
      • Lebel D.
      • Bussières J.-F.
      Accidents and incidents related to intravenous drug administration: A pre–post study following implementation of smart pumps in a teaching hospital.
      ;
      • Manrique-Rodríguez S.
      • Sánchez-Galindo A.C.
      • López-Herce J.
      • Calleja-Hernández M.
      • Martínez-Martínez F.
      • Iglesias-Peinado I.
      • Fernández-Llamazares C.M.
      Impact of implementing smart infusion pumps in a pediatric intensive care unit.
      ;
      • Subramanyam R.
      • Mahmoud M.
      • Buck D.
      • Varughese A.
      Infusion medication error reduction by two-person verification: A quality improvement initiative.
      ), computer assisted drug calculations, barriers to reduce interruptions during drug calculations and double checking before intravenous administration were used in one study each (
      • Colligan L.
      • Guerlain S.
      • Steck S.E.
      • Hoke T.R.
      Designing for distractions: A human factors approach to decreasing interruptions at a centralised medication station.
      ;
      • Subramanyam R.
      • Mahmoud M.
      • Buck D.
      • Varughese A.
      Infusion medication error reduction by two-person verification: A quality improvement initiative.
      ;
      • Yamamoto L.
      • Kanemori J.
      Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration.
      ).
      Smart infusion pump interventions involved provision of training for all nursing staff in programing medicine administration pumps. These smart pumps have safety software with built in drug libraries and drug infusion guardrails or limits to reduce probability of error occurrence. Training covered the expected and appropriate operation of the pumps as well as the expected change in practice. The process change involved use of itemised checklist, for compliance to ensure all steps of safe drug administration were followed to reduce drug errors. Pocket cards with steps to prevent errors in the administration of medications were given to all clinicians (
      • Otero P.
      • Leyton A.
      • Mariani G.
      • Ceriani Cernadas J.M.
      Medication errors in pediatric inpatients: Prevalence and results of a prevention program.
      ).
      Meta-analysis of interventions to reduce MAEs.
      Ten studies were included in a meta-analysis of interventions to reduce MAEs (Fig. 2). Three studies (
      • Bertsche T.
      • Bertsche A.
      • Krieg E.M.
      • Kunz N.
      • Bergmann K.
      • Hanke G.
      • Haefeli W.E.
      Prospective pilot intervention study to prevent medication errors in drugs administered to children by mouth or gastric tube: A programme for nurses, physicians and parents.
      ;
      • 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.
      ;
      • Otero P.
      • Leyton A.
      • Mariani G.
      • Ceriani Cernadas J.M.
      Medication errors in pediatric inpatients: Prevalence and results of a prevention program.
      ) had their results presented in odds ratio (OR) and for the other seven studies, we used pre and post intervention data provided to calculate OR. Calculated OR for individual studies are presented in Table 1. The meta-analysis showed a pooled OR 0.36 (95% Confidence Interval (CI) 0.21–0.63) P = 0.0003) for test of overall effect. The analysis demonstrates an associated 64% reduction in medicines administration errors post intervention. However a high heterogeneity (I2 = 98%) was observed demonstrating high variation in study outcomes between included studies. No subgroup group analysis was performed.
      Fig. 2
      Fig. 2Meta-analysis of interventions to reduce MAEs.

      Publication bias

      Publication bias was visually assessed using funnel plot developed using Rev. Man5. The plot was asymmetric indicating a possible risk of publication bias (Fig. 3 Funnel Plot).

      Narrative synthesis

      Studies not included in the meta-analysis presented their results in various forms. Four studies (
      • Hebbar K.B.
      • Colman N.
      • Williams L.
      • Pina J.
      • Davis L.
      • Bost J.E.
      • Frank G.
      A quality initiative: A system-wide reduction in serious medication events through targeted simulation training.
      ;
      • Manrique-Rodríguez S.
      • Sánchez-Galindo A.C.
      • López-Herce J.
      • Calleja-Hernández M.
      • Martínez-Martínez F.
      • Iglesias-Peinado I.
      • Fernández-Llamazares C.M.
      Impact of implementing smart infusion pumps in a pediatric intensive care unit.
      ;
      • McSweeney J.
      • Rosenholm E.
      • Penny K.
      • Mullen M.P.
      • Kulik T.J.
      Improving safety of intravenous prostacyclin administration to pediatric patients with pulmonary hypertension.
      ;
      • Simpson J.H.
      • Lynch R.
      • Grant J.
      • Alroomi L.
      Reducing medication errors in the neonatal intensive care unit.
      ) showed a significant reduction in MAEs after interventions.
      • Hebbar K.B.
      • Colman N.
      • Williams L.
      • Pina J.
      • Davis L.
      • Bost J.E.
      • Frank G.
      A quality initiative: A system-wide reduction in serious medication events through targeted simulation training.
      reported a decrease in MAE events from 2.5 to 1.4 per month (risk ratio (RR) 1.78, 95% CI 1.03–3.1 p = 0.02) during the 20 months rollout of a targeted simulation training to reduce serious medication events. A further reduction of monthly error events to 0.86 at 7 months post intervention was reported demonstrating a 63% decrease in MAEs from baseline period (RR = 2.9, 95% CI = 1.2–8.5, P = 0.014).
      In a study by
      • Manrique-Rodríguez S.
      • Sánchez-Galindo A.C.
      • López-Herce J.
      • Calleja-Hernández M.
      • Martínez-Martínez F.
      • Iglesias-Peinado I.
      • Fernández-Llamazares C.M.
      Impact of implementing smart infusion pumps in a pediatric intensive care unit.
      , the intervention (use of smart infusion pumps) intercepted 92 user programming errors rated as potential harm to the patient. The authors concluded that using smart infusion pump programming such as pump drug library, defined hard limits for infusion rates is associated with a 49% potential reduction or intercepting drug errors of moderate, serious or catastrophically severe cases. One study (
      • Colligan L.
      • Guerlain S.
      • Steck S.E.
      • Hoke T.R.
      Designing for distractions: A human factors approach to decreasing interruptions at a centralised medication station.
      ) implemented the barriers to reduce interruptions during drug calculation and preparation. They measured mean interruption rate per minute. They reported a significant mean interruption reduction from 1.4 pre-intervention to 0.27 post-intervention, p < 0.01.
      For studies that involved process and policy changes (
      • Kanjia M.K.
      • Adler A.C.
      • Buck D.
      • Varughese A.M.
      Increasing compliance of safe medication administration in pediatric anesthesia by use of a standardized checklist.
      ;
      • Subramanyam R.
      • Mahmoud M.
      • Buck D.
      • Varughese A.
      Infusion medication error reduction by two-person verification: A quality improvement initiative.
      ) uptake of process change as part of the interventions increased to 97% and from 0 to 90% respectively. The Northern Ireland study (
      • Stewart M.
      • Purdy J.
      • Kennedy N.
      • Burns A.
      An interprofessional approach to improving paediatric medication safety.
      ) targeted fourth year medical students and third year nursing students to deliver an education programme through teaching and workshop training to raise awareness on paediatric medication safety. After the intervention, students reported an increase in their knowledge and awareness of paediatric medication safety; with pre and post mean scores of 53.9 vs 69.8 (mean difference 15.9, 95% CI 10.4–21.4 p < 0.001), and shared learning experience on medication safety pre and post mean scores 67.9 vs 76.6 (mean difference 8.9, 95% CI 4.3–13.1 p < 0.001).

      Discussion

      The current review provides an update on intervention strategies to reduce medication administration errors in paediatric and neonates. Causes of medication errors during administration are multifactorial sometimes requiring multi-faceted interventions to address the root cause. This is reflected in our findings. The seven interventions identified included; education projects, medication information services, clinical pharmacist involvement, double checking, barriers to reduce interruptions during drug calculation and preparation, implementation of smart pumps (new technology) and improvement strategies. Most studies performed bundle as opposite to single interventions. Similarly to what has been observed in previous reviews, all included studies were single arm, pre and post design without a comparative, concurrent control group (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ;
      • Nguyen M.-N.R.
      • Mosel C.
      • Grzeskowiak L.E.
      Interventions to reduce medication errors in neonatal care: A systematic review.
      ). All interventions demonstrated a reduction in medication errors.
      In comparison to other similar recent reviews (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ;
      • Nguyen M.-N.R.
      • Mosel C.
      • Grzeskowiak L.E.
      Interventions to reduce medication errors in neonatal care: A systematic review.
      ;
      • Rinke M.L.
      • Bundy D.G.
      • Velasquez C.A.
      • Rao S.
      • Zerhouni Y.
      • Lobner K.
      • Miller M.R.
      Interventions to reduce pediatric medication errors: A systematic review.
      ;
      • Santesteban E.
      • Arenas S.
      • Campino A.
      Medication errors in neonatal care: A systematic review of types of errors and effectiveness of preventive strategies.
      ), in this review we performed a meta-analysis in ten studies with pooled size of effect OR showing a 64% associated reduction in MAEs after intervention. Methodological and study results presentation heterogeneity was observed in included studies. This variation precluded meta-analysis for some of studies.
      One of the predominant reason children are at greater risk from medication errors is the nature of drug dosages that are calculated based on the child's weight or body surface (
      • Wong I.C.
      • Wong L.Y.
      • Cranswick N.E.
      Minimising medication errors in children.
      ). However, weight can change during hospitalisation period and recalculation of drug dosages becomes a necessity particularly in neonates. As such, in addressing this key element, all education program interventions observed included elements of dose calculations, with some offering nursing staff further support until competency is achieved. Accurate medicine administration calculations is an essential part of patient safety and nurses competency such that it has become part of the curriculum with nursing schools dedicating time and effort to teach their students how to calculate drug doses and subsequently test them for these skills (
      • Rowe C.
      • Koren T.
      • Koren G.
      Errors by paediatric residents in calculating drug doses.
      ).
      It has previously been hypothesised that a bundle interventional approach, that is using more than one intervention with more than one function has an additive advantage on reducing medication errors (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ). This is considerably plausible as individual interventions often target different aspects of the medication management and administration process demonstrating that a combination of interventions is most likely required to achieve a significant reduction in MAEs (
      • Nguyen M.-N.R.
      • Mosel C.
      • Grzeskowiak L.E.
      Interventions to reduce medication errors in neonatal care: A systematic review.
      ). Therefore investigating and categorising different types of medication errors in accordance to the local context is a necessary step as part of designing and before implementing any proposed intervention.
      Several studies (
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      ;
      • Campino A.
      • Santesteban E.
      • Pascual P.
      • Sordo B.
      • Arranz C.
      • Unceta M.
      • Lopez-de-Heredia I.
      Strategies implementation to reduce medicine preparation error rate in neonatal intensive care units.
      ;
      • Raja Lope R.J.
      • Boo N.Y.
      • Rohana J.
      • Cheah F.C.
      A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.
      ) have demonstrated that to reduce medication errors, a change in the patient safety culture is of necessity coupled with specific training to promote effective sustainable change. To this effect, the role of structured educational intervention component as part of a MAE preventive strategy is worth noting. Thirteen studies (72%) out of 18 included studies in this review included an education component. Two previous reviews on a similar topic reported 94% (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ), and 30% (
      • Nguyen M.-N.R.
      • Mosel C.
      • Grzeskowiak L.E.
      Interventions to reduce medication errors in neonatal care: A systematic review.
      ) of included studies having either a staff or medication education component as part of the intervention strategy. Primarily the education aspects of the interventions are focused on increasing and addressing medication knowledge and understanding. This is often delivered in form of simulations or lectures addressing potential error prone points in the medication administration process (
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      ;
      • Campino A.
      • Santesteban E.
      • Pascual P.
      • Sordo B.
      • Arranz C.
      • Unceta M.
      • Lopez-de-Heredia I.
      Strategies implementation to reduce medicine preparation error rate in neonatal intensive care units.
      ). The use of simulation techniques during teaching sessions has been reported to have a substantial effect in medication administration error reduction (
      • 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.
      ). A systematic review of 15 studies on educational interventions alone to improve prescribing quality provided no definitive conclusion (
      • Ross S.
      • Loke Y.K.
      Do educational interventions improve prescribing by medical students and junior doctors? A systematic review.
      ), which might suggest that education programmes are impactful only as part of bundle as opposed to stand alone intervention. However studies included in this review using education interventions alone to address medication errors during administration (
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      ;
      • Campino A.
      • Santesteban E.
      • Pascual P.
      • Sordo B.
      • Arranz C.
      • Unceta M.
      • Lopez-de-Heredia I.
      Strategies implementation to reduce medicine preparation error rate in neonatal intensive care units.
      ;
      • Raja Lope R.J.
      • Boo N.Y.
      • Rohana J.
      • Cheah F.C.
      A quality assurance study on the administration of medication by nurses in a neonatal intensive care unit.
      ;
      • Stewart M.
      • Purdy J.
      • Kennedy N.
      • Burns A.
      An interprofessional approach to improving paediatric medication safety.
      ) demonstrated reduction in drug errors post intervention, although one of the studies concluded that the reduction was insufficient to achieve an adequate level of medication safety (
      • 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.
      ).
      In this review, another commonly observed intervention used as part of bundle is the collaboration of clinical pharmacists on medicine activities with nurses. Involvement of clinical pharmacists has shown to prevent 58% of medication errors and 72% of potentially high risk errors (
      • Fortescue E.B.
      • Kaushal R.
      • Landrigan C.P.
      • McKenna K.J.
      • Clapp M.D.
      • Federico F.
      • Bates D.W.
      Prioritizing strategies for preventing medication errors and adverse drug events in pediatric inpatients.
      ). The presence of clinical pharmacists may help nurses to make informed clinical decisions at any point during drug administration process. Pharmacokinetic monitoring, up-to-date information on reconstitution and dilution of drugs, compatibility of intravenous medication and collaboration with other healthcare professionals to optimise therapeutic plans are roles a clinical pharmacist can undertake (
      • Campino A.
      • Lopez-Herrera M.C.
      • Lopez-de-Heredia I.
      • Valls-i-Soler A.
      Educational strategy to reduce medication errors in a neonatal intensive care unit.
      ;
      • Prot-Labarthe S.
      • Di Paolo E.R.
      • Lavoie A.
      • Quennery S.
      • Bussières J.F.
      • Brion F.
      • Bourdon O.
      Pediatric drug-related problems: A multicenter study in four French-speaking countries.
      ).
      Study limitations.
      There are various types of medicine errors; prescribing, preparation and dispensing, monitoring and administration errors and these errors often influence the outcome of each other. Also the type of errors might be influenced more by one healthcare professional group, for example medication prescription is mainly the medical team's responsibility while drug administration is often done by the nursing staff. This review focused on drug administration error reduction interventions only, which might not give a true picture of the challenges and complexities to be considered when implementing such interventions. Some studies that predominantly looked at other drug error types with minimum emphasis on medicines administration errors could have been missed. However we performed a comprehensive search strategy to ensure inclusion of all possible studies.
      There are frameworks such as the
      • Cochrane Effective Practice and Organisation of Care (EPOC)
      EPOC taxonomy.
      taxonomy of intervention and the Behaviour Change Wheel (BCW) approach (
      • Michie S.
      • van Stralen M.M.
      • West R.
      The behaviour change wheel: A new method for characterising and designing behaviour change interventions.
      ), which have categorised interventions to improve the quality of care or reduce errors (
      • Maaskant J.M.
      • Vermeulen H.
      • Apampa B.
      • Fernando B.
      • Ghaleb M.A.
      • Neubert A.
      • Soe A.
      Interventions for reducing medication errors in children in hospital.
      ;
      • Smith S.M.
      • Wallace E.
      • O’Dowd T.
      • Fortin M.
      Interventions for improving outcomes in patients with multimorbidity in primary care and community settings.
      ). The EPOC taxonomy stratifies interventions into four groups; professional, organisational, financial and regulatory depending on the target. On the other hand, the BCW classify interventions based on their function; environmental restructuring, education, persuasion, incentivisation, coercion, training, restriction, modelling and enablement. While such frameworks have been used in previous reviews (
      • Bannan D.F.
      • Tully M.P.
      Bundle interventions used to reduce prescribing and administration errors in hospitalized children: A systematic review.
      ;
      • Nguyen M.-N.R.
      • Mosel C.
      • Grzeskowiak L.E.
      Interventions to reduce medication errors in neonatal care: A systematic review.
      ) in this review we grouped identified interventions from included studies together according to their similarity for clarity to the readers.

      Implications for practice

      Findings from this review broadly highlight the following three aspects for consideration by practicing nurses and their respective health care organisation; a) medication errors are multifaceted and the causes of errors need to be identified prior to implementation of appropriate interventions, b) medication safety education is an integral element of interventions in a bid to reduce administration errors and c) interdisciplinary collaboration in the medication process contributes to the reduction of medication administration errors. In view of the outlined considerations, the following, bundle interventions could be considered most beneficial to practicing nurses. Education interventions (which include but not limited to lectures, workshops, simulations and practical training) and provision of relevant drug information services remain predominantly fundamental in reducing medicines administration errors. Regular education sessions and updates on medicines administration could also be used as part of nursing staff continuous professional development (CPD) to enhance evidence based practice. The multidisciplinary nature of healthcare provision requires the involvement of clinical pharmacy services to ensure delivery of safe medications care. This affords practising nurses easy access to pharmacists during working hours and out of hours if further discussion is required (
      • Abuelsoud N.
      Pharmacy quality improvement project to enhance the medication management process in pediatric patients.
      ). The use of smart pumps with medicines library and guard rails are now prevalent and part of standard care in most clinical areas with provision of equipment training a prerequisite.

      Conclusion

      Administration of medicines to children via any route can sometime be a complex process requiring special attention and multifaceted interventions to reduce and or avoid potential errors. There is no ‘one size fit all’ solution in reducing medication administration errors. Identifying causes of errors within the local context and understanding conditions and mechanisms that exacerbate such practice performances is necessary in designing or choosing potential effective interventions from the list outlined in this review. Continuous monitoring and evaluation of interventions used in clinical practice is paramount for measuring effectiveness and ensuring patient safety.

      Funding

      None.

      Availability of data and material

      N/A

      Code availability

      N/A

      Authors' contributions

      Marufu and Manning conceptualized and designed the study. Hendron performed the search strategy, Marufu, Bower and Manning performed data extraction. All the authors were involved in data analysis and have contributed to the drafting, critical review and revision of the manuscript. All authors have approved the final manuscript.

      Conflicts of interest

      Dr. Joseph C. Manning is a current recipient of an NIHR HEE funded ICA Clinical Lectureship [ ICA-CL-2018-04-ST2-009 ]. The views expressed in this article are those of the authors and not necessarily those of the NIHR or Department of Health and Social Care, UK.

      Appendix A. Supplementary data

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