Skip to main content
SpringerLink
Log in

Patient- and physician-related risk factors for hyperkalaemia in potassium-increasing drug–drug interactions

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Hyperkalaemia due to potassium-increasing drug–drug interactions (DDIs) is a clinically important adverse drug event. The purpose of this study was to identify patient- and physician-related risk factors for the development of hyperkalaemia.

Methods

The risk for adult patients hospitalised in the University Hospital Zurich between 1 December 2009 and 31 December 2011 of developing hyperkalaemia was correlated with patient characteristics, number, type and duration of potassium-increasing DDIs and frequency of serum potassium monitoring.

Results

The 76,467 patients included in this study were prescribed 8,413 potentially severe potassium-increasing DDIs. Patient-related characteristics associated with the development of hyperkalaemia were pulmonary allograft [relative risk (RR) 5.1; p < 0.0001), impaired renal function (RR 2.7; p < 0.0001), diabetes mellitus (RR 1.6; p = 0.002) and female gender (RR 1.5; p = 0.007). Risk factors associated with medication were number of concurrently administered potassium-increasing drugs (RR 3.3 per additional drug; p < 0.0001) and longer duration of the DDI (RR 4.9 for duration ≥6 days; p < 0.0001). Physician-related factors associated with the development of hyperkalaemia were undetermined or elevated serum potassium level before treatment initiation (RR 2.2; p < 0.001) and infrequent monitoring of serum potassium during a DDI (interval >48 h: RR 1.6; p < 0.01).

Conclusion

Strategies for reducing the risk of hyperkalaemia during potassium-increasing DDIs should consider both patient- and physician-related risk factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kohn LT CJ, Donaldson MS (eds) (1999) To err is human. Building a safer health system. Committee on Quality in Health Care, Institute of Medicine, Washington D.C.

    Google Scholar 

  2. Leendertse AJ, Egberts AC, Stoker LJ, van den Bemt PM (2008) Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands. Arch Intern Med 168(17):1890–1896. doi:10.1001/archinternmed.2008.3

    PubMed  Google Scholar 

  3. Hamilton RA, Briceland LL, Andritz MH (1998) Frequency of hospitalization after exposure to known drug–drug interactions in a Medicaid population. Pharmacotherapy 18(5):1112–1120

    CAS  PubMed  Google Scholar 

  4. Sanchez Munoz-Torrero JF, Barquilla P, Velasco R, Fernandez Capitan Mdel C, Pacheco N, Vicente L, Chicon JL, Trejo S, Zamorano J, Lorenzo Hernandez A (2010) Adverse drug reactions in internal medicine units and associated risk factors. Eur J Clin Pharmacol 66(12):1257–1264. doi:10.1007/s00228-010-0866-6

    Article  PubMed  Google Scholar 

  5. Zwart-van Rijkom JE, Uijtendaal EV, ten Berg MJ, van Solinge WW, Egberts AC (2009) Frequency and nature of drug-drug interactions in a Dutch university hospital. Br J Clin Pharmacol 68(2):187–193. doi:10.1111/j.1365-2125.2009.03443.x

    Article  CAS  PubMed  Google Scholar 

  6. Gennari FJ (2002) Disorders of potassium homeostasis. Hypokalemia and hyperkalemia. Crit Care Clin 18(2):273–288

    Article  CAS  PubMed  Google Scholar 

  7. van der Sijs H, Aarts J, Vulto A, Berg M (2006) Overriding of drug safety alerts in computerized physician order entry. J Am Med Inform Assoc 13(2):138–147. doi:10.1197/jamia.M1809

    Article  PubMed Central  PubMed  Google Scholar 

  8. Smithburger PL, Buckley MS, Bejian S, Burenheide K, Kane-Gill SL (2011) A critical evaluation of clinical decision support for the detection of drug-drug interactions. Expert Opin Drug Saf 10(6):871–882 doi:10.1517/14740338.2011.583916

    Google Scholar 

  9. Abarca J, Colon LR, Wang VS, Malone DC, Murphy JE, Armstrong EP (2006) Evaluation of the performance of drug-drug interaction screening software in community and hospital pharmacies. J Manag Care Pharm 12(5):383–389

    PubMed  Google Scholar 

  10. Oertle M (2012) Frequency and nature of drug-drug interactions in a Swiss primary and secondary acute care hospital. Swiss Med Wkly 142:w13522. doi:10.4414/smw.2012.13522

    PubMed  Google Scholar 

  11. Beeler PE, Eschmann E, Rosen C, Blaser J (2013) Use of an on-demand drug-drug interaction checker by prescribers and consultants: a retrospective analysis in a swiss teaching hospital. Drug Saf 36(6):427–434. doi:10.1007/s40264-013-0022-1

    Article  PubMed  Google Scholar 

  12. Uijtendaal EV, Zwart-van Rijkom JE, van Solinge WW, Egberts TC (2011) Frequency of laboratory measurement and hyperkalaemia in hospitalised patients using serum potassium concentration increasing drugs. Eur J Clin Pharmacol 67(9):933–940. doi:10.1007/s00228-011-1028-1

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Zopf Y, Rabe C, Neubert A, Janson C, Brune K, Hahn EG, Dormann H (2009) Gender-based differences in drug prescription: relation to adverse drug reactions. Pharmacology 84(6):333–339. doi:10.1159/000248311

    Article  CAS  PubMed  Google Scholar 

  14. Klein U, Klein M, Sturm H, Rothenbuhler M, Huber R, Stucki P, Gikalov I, Keller M, Hoigne R (1976) The frequency of adverse drug reactions as dependent upon age, sex and duration of hospitalization. Int J Clin Pharmacol Biopharm 13(3):187–195

    CAS  PubMed  Google Scholar 

  15. Henz S, Maeder MT, Huber S, Schmid M, Loher M, Fehr T (2008) Influence of drugs and comorbidity on serum potassium in 15 000 consecutive hospital admissions. Nephrol Dial Transplant 23(12):3939–3945. doi:10.1093/ndt/gfn380

    Article  PubMed  Google Scholar 

  16. Johnson ES, Weinstein JR, Thorp ML, Platt RW, Petrik AF, Yang X, Anderson S, Smith DH (2010) Predicting the risk of hyperkalemia in patients with chronic kidney disease starting lisinopril. Pharmacoepidemiol Drug Saf 19(3):266–272. doi:10.1002/pds.1923

    Article  CAS  PubMed  Google Scholar 

  17. Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA (2004) Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 351(6):543–551. doi:10.1056/NEJMoa040135

    Article  CAS  PubMed  Google Scholar 

  18. Muzzarelli S, Maeder MT, Toggweiler S, Rickli H, Nietlispach F, Julius B, Burkard T, Pfisterer ME, Brunner-La Rocca HP (2012) Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy. Am J Cardiol 109(5):693–698. doi:10.1016/j.amjcard.2011.10.027

    Article  CAS  PubMed  Google Scholar 

  19. Raebel MA, Ross C, Xu S, Roblin DW, Cheetham C, Blanchette CM, Saylor G, Smith DH (2010) Diabetes and drug-associated hyperkalemia: effect of potassium monitoring. J Gen Intern Med 25(4):326–333. doi:10.1007/s11606-009-1228-x

    Article  PubMed Central  PubMed  Google Scholar 

  20. Hansten PD, Horn JR, Hazlet TK (2001) ORCA: OpeRational ClassificAtion of drug interactions. J Am Pharm Assoc (Wash) 41(2):161–165

    CAS  Google Scholar 

  21. Ho JM, Juurlink DN, Cavalcanti RB (2010) Hypokalemia following polyethylene glycol-based bowel preparation for colonoscopy in older hospitalized patients with significant comorbidities. Ann Pharmacother 44(3):466–470. doi:10.1345/aph.1M341

    Article  CAS  PubMed  Google Scholar 

  22. Bonini P, Ceriotti F, Keller F, Brauer P, Stolz H, Pascual C, Garcia Beltran L, Vonderschmitt DJ, Pei P (1992) Multicentre evaluation of the Boehringer Mannheim/Hitachi 747 analysis system. Eur J Clin Chem Clin Biochem 30(12):881–899

    CAS  PubMed  Google Scholar 

  23. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41

    Article  CAS  PubMed  Google Scholar 

  24. K/DOQI (2002) Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39[2 Suppl 1]:S1–S266

    Google Scholar 

  25. Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat Theory Appl 6:65–70

    Google Scholar 

  26. Clopper CJ, Pearson ES (1934) The use of confidence or fiducial limits illustratied in the case of the binomial. Biometrika 26(4):404–413. doi:10.1093/biomet/26.4.404

    Article  Google Scholar 

  27. Indermitte J, Burkolter S, Drewe J, Krahenbuhl S, Hersberger KE (2007) Risk factors associated with a high velocity of the development of hyperkalaemia in hospitalised patients. Drug Saf 30(1):71–80

    Article  CAS  PubMed  Google Scholar 

  28. Ponce SP, Jennings AE, Madias NE, Harrington JT (1985) Drug-induced hyperkalemia. Medicine (Baltimore) 64(6):357–370

    Article  CAS  Google Scholar 

  29. Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD, Van Bergen RC, Lipton RB (2004) Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc 44(2):136–141

    Article  Google Scholar 

  30. Wang LM, Wong M, Lightwood JM, Cheng CM (2010) Black box warning contraindicated comedications: concordance among three major drug interaction screening programs. Ann Pharmacother 44(1):28–34. doi:10.1345/aph.1M475

    Article  CAS  PubMed  Google Scholar 

  31. Uribarri J, Oh MS, Carroll HJ (1990) Hyperkalemia in diabetes mellitus. J Diabet Complications 4(1):3–7

    Article  CAS  PubMed  Google Scholar 

  32. Schuurmans MM, Tini GM, Zuercher A, Hofer M, Benden C, Boehler A (2012) Practical approach to emergencies in lung transplant recipients: how we do it. Respiration 84(2):163–175. doi:10.1159/000339345

    Article  PubMed  Google Scholar 

  33. Knoop C, Rondelet B, Dumonceaux M, Estenne M (2010) Medical complications of lung transplantation. Rev Pneumol Clin 67(1):28–49. doi:10.1016/j.pneumo.2010.08.002

    Article  CAS  PubMed  Google Scholar 

  34. Ramirez E, Rossignoli T, Campos AJ, Munoz R, Zegarra C, Tong H, Medrano N, Borobia AM, Carcas AJ, Frias J (2012) Drug-induced life-threatening potassium disturbances detected by a pharmacovigilance program from laboratory signals. Eur J Clin Pharmacol 69(1):97–110. doi:10.1007/s00228-012-1303-9

    Article  PubMed  Google Scholar 

Download references

Disclosure of conflict of interests

None.

Author information

Authors and Affiliations

  1. Research Centre for Medical Informatics, Directorate of Research and Education, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Emmanuel Eschmann, Patrick E. Beeler & Jürg Blaser

  2. Division of Internal Medicine, Kreisspital für das Freiamt Muri, Spitalstrasse 144, 5630, Muri, Switzerland

    Vladimir Kaplan

  3. Division of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Markus Schneemann

  4. Directorate of Research and Education, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Gregor Zünd

Authors
  1. Emmanuel Eschmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick E. Beeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vladimir Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Markus Schneemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gregor Zünd
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jürg Blaser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emmanuel Eschmann.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

(PDF 14.7 kb)

Online Resource 2

(PDF 26 kb)

Online Resource 3

(PDF 48 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eschmann, E., Beeler, P.E., Kaplan, V. et al. Patient- and physician-related risk factors for hyperkalaemia in potassium-increasing drug–drug interactions. Eur J Clin Pharmacol 70, 215–223 (2014). https://doi.org/10.1007/s00228-013-1597-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-013-1597-2

Keywords

Search

Navigation