Drug-induced life-threatening potassium disturbances detected by a pharmacovigilance program from laboratory signals.
OBJECTIVE
Detection and reporting of drug-induced life-threatening potassium disturbances and the study of associated factors under a Pharmacovigilance Program using Laboratory Signals at a Hospital (PPLSH) during a 2-year period.


METHODS
All serum potassium levels <2 mmol/l or >7 mmol/l detected at admission to the hospital, including those of patients who died in the emergency ward or during hospitalization, were monitored prospectively from January 2009 through to December 2010. The incidence rate of each etiology of potassium disturbances was calculated. Factors associated with drug-induced potassium disturbances were detected using a multiple logistic regression model.


RESULTS
The incidence of true life-threatening drug-induced hyper- and hypokalemia events was 3 and 4.32 (Poisson 95 % confidence interval 1.62-10.24), respectively, per 10,000 admissions. Of the severe potassium disturbances, 32.3 % were drug-induced, and 23 % were lethal. We identified previously undescribed pharmacological causes of hyperkalemia (risedronate, doxazosin) and hypokalemia (acyclovir, teicoplanin, cefepime, meropenem, dexketoprofen colistimethate). Significant predictor factors associated with drug-induced hyperkalemia were the use of polypharmacy (>5 drugs), age (>74 years), sex (female) and kidney disease (glomerular filtration rate <60 ml/min) with the presence of ≥4 comorbid conditions. The only predictor of drug-induced hypokalemia was the use of >5 drugs. The triggering factor associated with drug-induced hyperkalemia and hypokalemia was azotemia and hypoalbuminemia, respectively.


CONCLUSIONS
Drug-induced life-threatening potassium disturbances remain a relevant problem. Potential strategies for prevention are to avoid polypharmacy, early discontinuation of treatment of drugs causing hyperkalemia or nephrotoxicity in cases of various clinical situations (cardiac descompensation, infection, hypovolemia) or obstructive causes, and insistence on albumin control during hospitalization.
Clinical Pharmacology Deparment, Hospital Universitario La Paz (IdiPaz), School of Medicine, Universidad Autónoma de Madrid, Arzobispo Morcillo s/n, 28029 Madrid, Spain. elena.ramirez@uam.es
Elena
E
Ramírez
Tomás
T
Rossignoli
Armando J
AJ
Campos
Raúl
R
Muñoz
Claudia
C
Zegarra
Hoi
H
Tong
Nicolás
N
Medrano
Alberto M
AM
Borobia
Antonio J
AJ
Carcas
Jesús
J
Frías
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006785:Hospitals, University / Q000706:statistics & numerical data; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D007008:Hypokalemia / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D007223:Infant; D007753:Laboratories; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D011188:Potassium / Q000097:blood; D013030:Spain
D011188:Potassium