International Journal of Clinical Pharmacy

, Volume 41, Issue 1, pp 179–188 | Cite as

Impact of medication therapy management on pharmacotherapy safety in an intensive care unit

  • Renato Rocha Martins
  • Lunara Teles Silva
  • Flavio Marques LopesEmail author
Research Article


Background Drug-related problems are mostly preventable or predictable circumstances that may impact on health outcomes. Clinical pharmacy activities such as medication therapy management can identify and solve these problems, with potential to improve medication safety and effectiveness. Objective To evaluate ability of medication therapy management service to detect drug-related problems and prevent adverse drug events. This study also aimed to assess the risk factors for drugrelated problem occurrence. Setting Medical intensive care unit of a public tertiary hospital in Brazil. Methods Patients were evaluated by a clinical pharmacist, who provided medication therapy management service. Detected drug-related problems were categorized according to the Pharmaceutical Care Network Europe methodology and analyzed in multinomial regression to identify risk factors. Main outcome measure Potential risk factors for drug-related problem occurrence. Results The proposed medication therapy management service allowed detection of 170 drug-related problems that had potential to reach patients causing harm and other 50 unavoidable adverse events. Drug-related problems identified were more often associated with antibacterial use, caused by improper combinations or inadequate drug dosage. These problems required interventions that were accepted by the multidisciplinary team, resulting in more than 85% adherence and total problem solving. Main risk factors identified were previous diagnosis of kidney injury (OR = 8.38), use of midazolam (OR = 7.96), furosemide (OR = 5.87) and vancomycin (OR = 4.82). Conclusion Medication therapy management proved to be an effective method not only for drug-related problem detection, but also for adverse drug event prevention, contributing to improve patient safety.


Adverse drug events Brazil Clinical pharmacists Drug-related problems Medication therapy management PCNE DRP-classification 



The authors thank Prof. Nathalie de L. S. Dewulf and Prof. Ana Elisa B. C. Silva for their suggestions, support and encouragement.


This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001—grants AUXPE 1665/2016 and Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG).

Conflicts of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA. 1997;277:301–6.Google Scholar
  2. 2.
    Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA, et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA. 1997;277:307–11.Google Scholar
  3. 3.
    Kane-Gill SL, Kirisci L, Verrico MM, Rothschild JM. Analysis of risk factors for adverse drug events in critically ill patients. Crit Care Med. 2012;40(3):823–8.Google Scholar
  4. 4.
    Rothschild JM, Landrigan CP, Cronin JW, Kaushal R, Lockley SW, Burdick E, et al. The Critical Care Safety Study: the incidence and nature of adverse events and serious medical errors in intensive care. Crit Care Med. 2005;33:1694–700.Google Scholar
  5. 5.
    Pharmaceutical Care Network Europe Foundation. PCNE Classification for drug related problems version 7.0. 2016. Accessed 02 Aug 2018.
  6. 6.
    Ridley SA, Booth SA, Thompson CM. Intensive Care Society’s Working Group on Adverse Incidents: prescription errors in UK critical care units. Anaesthesia. 2004;59:1193–200.Google Scholar
  7. 7.
    Herout PM, Erstad BL. Medication errors involving continuously infused medications in a surgical intensive care unit. Crit Care Med. 2004;32:428–32.Google Scholar
  8. 8.
    Latif A, Rawat N, Pustavoitau A, Pronovost PJ, Pham JC. National study on the distribution, causes, and consequences of voluntarily reported medication errors between the ICU and non-ICU settings. Crit Care Med. 2013;41(2):389–98.Google Scholar
  9. 9.
    Abdelaziz K, Abdelrahim ME. Identification and categorization of drug-related problems on admission to an adult intensive care unit. Eur J Hosp Pharm. 2015;22:138–41.Google Scholar
  10. 10.
    Guignard B, Bonnabry P, Perrier A, Dayer P, Desmeules J, Samer CF. Drug-related problems identification in general internal medicine: the impact and role of the clinical pharmacist and pharmacologist. Eur J Intern Med. 2015;26:399–406.Google Scholar
  11. 11.
    Leape LL, Cullen DJ, Clapp MD, Burdick E, Demonaco HJ, Erickson JI, et al. Pharmacist participation on physician rounds and adverse drug events in the intensive care unit. JAMA. 1999;282(3):267–70.Google Scholar
  12. 12.
    Calabrese AD, Erstad BL, Brandl K, Barletta JF, Kane SL, Sherman DS. Medication administration errors in adult patients in the ICU. Intensive Care Med. 2001;27(10):1592–8.Google Scholar
  13. 13.
    Kane SL, Weber RJ, Dasta JF. The impact of critical care pharmacists on enhancing patient outcomes. Intensive Care Med. 2003;29(5):691–8.Google Scholar
  14. 14.
    Kim JM, Park SJ, Sohn YM, Lee YM, Yang CS, Gwak HS, et al. Development of clinical pharmacy services for intensive care units in Korea. Springerplus. 2014;3:34.Google Scholar
  15. 15.
    Metnitz PG, Moreno RP, Almeida E, Jordan B, Bauer P, Campos RA, et al. SAPS 3 - From evaluation of the patient to evaluation of the intensive care unit. Part 1: objectives, methods and cohort description. Intensive Care Med. 2005;31:1336–44.Google Scholar
  16. 16.
    Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, et al. SAPS 3—from evaluation of the patient to evaluation of the intensive care unit. Part 2: development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med. 2005;31:1345–55.Google Scholar
  17. 17.
    Vincent JL, Moreno R, Takala J, Willatts S, DeMendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10.Google Scholar
  18. 18.
    Jiang SP, Chen J, Zhang XG, Lu XY, Zhao QW. Implementation of pharmacists’ interventions and assessment of medication errors in an intensive care unit of a Chinese tertiary hospital. Ther Clin Risk Manag. 2014;10:861–6.Google Scholar
  19. 19.
    World Health Organization. Medication without harm—global patient safety challenge on medication safety. Geneva: World Health Organization; 2017. Accessed 02 Aug 2018.
  20. 20.
    Klopotowska JE, Kuiper R, van Kan HJ, de Pont AC, Dijkgraaf MG, Lie-A-Huen L, et al. On-ward participation of a hospital pharmacist in a Dutch intensive care unit reduces prescribing errors and related patient harm: an intervention study. Crit Care. 2010;14:R174.Google Scholar
  21. 21.
    Carayon P, Wetterneck TB, Cartmill R, Blosky MA, Bronw R, Kim R, et al. Characterizing the complexity of medication safety using a human factors approach: an observational study in two intensive care units. BMJ Qual Saf. 2014;23(1):56–65.Google Scholar
  22. 22.
    Sakuma M, Ida H, Nakamura T, Ohta Y, Yamamoto K, Seki S, et al. Adverse drug events and medication errors in Japanese paediatric inpatients: a retrospective cohort study. BMJ Qual Saf. 2014;23(10):830–7.Google Scholar
  23. 23.
    Ho CK, Mabasa VH, Leung VWY, Malyuk DL, Perrott JL. Assessment of clinical pharmacy interventions in the intensive care unit. Can J Hosp Pharm. 2013;66(4):212–8.Google Scholar
  24. 24.
    Kjeldsen LJ, Birkholm T, Fischer H, Graabæk T, Kibsdal KP, Ravn-Nielsen LV, et al. Characterization of drug-related problems identified by clinical pharmacy staff at Danish hospitals. Int J Clin Pharm. 2014;36:734.Google Scholar
  25. 25.
    Kucukarslan SN, Corpus K, Mehta N, Mlynarek M, Peters M, Stagner L, et al. Evaluation of a dedicated pharmacist staffing model in the medical intensive care unit. Hosp Pharm. 2013;48(11):922–30.Google Scholar
  26. 26.
    Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219–32.Google Scholar
  27. 27.
    Lucca JM, Ramesh M, Narahari GM, Minaz N. Impact of clinical pharmacist interventions on the cost of drug therapy in intensive care units of a tertiary care teaching hospital. J Pharmacol Pharmacother. 2012;3:242–7.Google Scholar
  28. 28.
    Vincent RJ, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.Google Scholar
  29. 29.
    Rivkin A, Yin H. Evaluation of the role of the critical care pharmacist in identifying and avoiding or minimizing significant drug-drug interactions in medical intensive care patients. J Crit Care. 2011;26(1):104.e1–6.Google Scholar
  30. 30.
    Smithburger PL, Kane-Gill SL, Seybert AL. Drug–drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved. Int J Pharm Pract. 2012;20:402–8.Google Scholar
  31. 31.
    Uijtendaal EV, van Harssel LLM, Hugenholtz GWK, Kuck EM, Zwart-van Rijkom JE, Cremer OL, et al. Analysis of potential drug-drug interactions in medical intensive care unit patients. Pharmacotherapy. 2014;34(3):213–9.Google Scholar
  32. 32.
    Beniasadi S, Farzanegan B, Alehashem M. Important drug classes associated with potential drug–drug interactions in critically ill patients: highlights for cardiothoracic intensivists. Ann Intensive Care. 2015;5:44.Google Scholar
  33. 33.
    Reis AMM, Cassiani SHB. Adverse drug events in an intensive care unit of a university hospital. Eur J Clin Pharmacol. 2011;67:625–32.Google Scholar
  34. 34.
    Letsas KP, Efremidis M, Kounas SP, Pappas LK, Gavrielatos G, Alexanian IP, et al. Clinical characteristics of patients with drug-induced QT interval prolongation and torsade de pointes: identification of risk factors. Clin Res Cardiol. 2009;98:208–12.Google Scholar
  35. 35.
    Lu TH, Lee YY, Tsai SC, Chien HY, Chang JC, Tseng JH, et al. The outcome of clinical pharmacists’ interventions in a Taiwanese Hospital on pharmacoeconomics and cost saving. J Exp Clin Med. 2014;6(4):139–42.Google Scholar
  36. 36.
    Franco Sereno MT, Pérez Serrano R, Ortiz Díaz-Miguel R, Espinosa González MC, Abdel-HadiÁlvarez H, Ambrós Checa A, et al. Pharmacist adscription to intensive care: generating synergies. Med Intensiva. 2018;S0210-5691(18):30052-4.Google Scholar
  37. 37.
    Bosma BE, van den Bemt PMLA, Melief PHGJ, van Bommel J, Tan SS, Hunfeld NGM. Pharmacist interventions during patient rounds in two intensive care units: clinical and financial impact. Neth J Med. 2018;76(3):115–24.Google Scholar
  38. 38.
    Claus BO, Robays H, Decruyenaere J, Annemans L. Expected net benefit of clinical pharmacy in intensive care medicine: a randomized interventional comparative trial with matched before-and-after groups. J Eval Clin Pract. 2014;20(6):1172–9.Google Scholar
  39. 39.
    Jiang SP, Zheng X, Li X, Lu XY. Effectiveness of pharmaceutical care in an intensive care unit from China: a pre- and post-intervention study. Saudi Med J. 2012;33(7):756–62.Google Scholar
  40. 40.
    Benkirane RR, R-Abouqal R, Haimeur CC, Ech Cherif S, El Kettani SS, Azzouzi AA, et al. Incidence of adverse drug events and medication errors in intensive care units: a prospective multicenter study. J Patient Saf. 2009;5(1):16–22.Google Scholar
  41. 41.
    Hisham M, Sivakumar MN, Veerasekar G. Impact of clinical pharmacist in an Indian Intensive Care Unit. Indian J Crit Care Med. 2016;20:78–83.Google Scholar
  42. 42.
    Anthes AM, Harinstein LM, Smithburger PL, Seybert AL, Kane-Gill SL. Improving adverse drug event detection in critically ill patients through screening intensive care unit transfer summaries. Pharmacoepidemiol Drug Saf. 2013;22(5):510–6.Google Scholar
  43. 43.
    Smithburger PL, Buckley MS, Culver MA, Sokol S, Lat I, Handler SM, et al. A multicenter evaluation of off-label medication use and associated adverse drug reactions in adult medical ICUs. Crit Care Med. 2015;43(8):1612–21.Google Scholar
  44. 44.
    Joshua L, Devi P, Guido S. Adverse drug reactions in medical intensive care unit of a tertiary care hospital. Pharmacoepidemiol Drug Saf. 2009;18(7):639–45.Google Scholar
  45. 45.
    Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL. Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units. Crit Care Med. 1997;25(8):1289–97.Google Scholar
  46. 46.
    Resar RR, Rozich JD, Simmonds T, Haraden CR. A trigger tool to identify adverse events in the intensive care unit. Jt Comm J Qual Patient Saf. 2006;32(10):585–90.Google Scholar
  47. 47.
    Fideles GM, Alcântara-Neto JM, Peixoto Júnior AA, Souza-Neto PJ, Tonete TL, Silva JEG, et al. Recomendações farmacêuticas em unidade de terapia intensiva: três anos de atividades clínicas. Rev Bras Ter Intensiva. 2015;27(2):149–54.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Laboratório de Pesquisa em Ensino e Serviços de Saúde (LaPESS), Faculdade de FarmáciaUniversidade Federal de Goiás – UFGGoiâniaBrazil
  2. 2.Divisão de FarmáciaHospital Geral de Goiânia Dr. Alberto RassiGoiâniaBrazil

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