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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.

Background: It was found that age and female gender are predisposing factors for hyponatremia in patients taking thiazides., Objective: To investigate whether a relationship exists between age and gender and serum sodium and potassium as well as the prevalence rates in a large population of patients presenting to the emergency department of a university hospital., Methods: In this retrospective analysis we gathered data on age, gender and current diuretic medication of all patients admitted to the emergency department of a large university hospital with measurement of serum sodium and potassium between January 1, 2009 and December 31, 2010. Prevalence rates of and risk factors for electrolyte disorders were calculated on the basis of these data., Results: A total of 20,667 patients were included in the analysis. Serum sodium levels declined significantly with increasing age while serum potassium rose, independent of diuretic medication at presentation. The prevalence rates of hyponatremia and hyperkalemia increased from 2.3% for hyponatremia in patients aged 16-21 years to 16.9% in patients aged >80 years and from 0.8% for hyperkalemia to 10.4%. In the regression analysis, age >60 years was a predictor for the presence of hyponatremia and hyperkalemia as was current use of diuretic medication. Male gender was associated with a decreased prevalence of hyponatremia and hypokalemia, while it was a predictor of hyperkalemia., Conclusions: Sodium levels were lower with increasing age, independent of diuretic intake, while potassium levels were higher. We found dramatically increasing prevalences of hyponatremia and hyperkalemia with increasing age, while no such effect could be found for hypernatremia and hypokalemia.

Electronic alerts for preventing hyperkalaemia during potassium-increasing drug-drug-interactions (DDIs) are often overridden due to their low specificity. Treatments of 76,467 inpatients were retrospectively analysed to establish more specific alerts. Alerting concepts for identifying DDIs that induced hyperkalaemia (serum potassium ≥5.5 mEq/l were compared. The positive predictive value (PPV) of alerts was 2.9% if they were triggered at onset of each potassium-increasing DDI. The PPV increased to 5.1% if alerts at onset were suppressed for serum potassium levels of &lt;4.0 mEq/l. The PPV rose to 24.2% with a novel approach, triggering alerts whenever an elevated potassium level of &gt;4.8 mEq/l was detected at onset or during the entire DDI period. Thus, triggering DDI alerts based on periodically monitored potassium levels may improve specificity of alerts and thereby reduce alert fatigue.

Computer-triggered reminders alerting physicians on every potentially harmful drug-drug-interaction (DDI) induce alert fatigue due to frequent messages of limited clinical relevance. On demand DDI-checks, however, are not commonly used by physicians. Optimal strategies for sustained quality assurance have to consider patients' risk factors and focus on the most significant DDIs only. An approach is proposed based on the analysis of concurrent prescription of potassium-sparing diuretics and potassium supplements (CPPP), which are the most frequent DDIs classified as contraindicated. Although the frequency of monitoring potassium serum levels declined during prolonged periods of CPPP, the likelihood of observing a hyperkalaemia increased. The median treatment period of CPPP was 3.3 days, whereas hyperkalaemia occurred after a median observation time of 4.5 days of CPPP. Thus, computer-triggered reminders for ordering potassium serum levels may be indicated if monitoring has been discontinued after 48h of CPPP.

Background/objective: Drugs have been recognised as a primary or contributing cause of hyperkalaemia, especially when administered to patients with underlying risk factors. The objective of this study was to analyse the influence of the known risk factors for hyperkalaemia on the velocity of the development of hyperkalaemia., Study Design/methods: Clinical characteristics, laboratory data and medication profiles of patients developing hyperkalaemia (serum potassium>or=5.0 mmol/L) hospitalised between 2000 and 2004 in the University Hospital Basel, Switzerland, were recorded. Factors associated with a high velocity of the development of hyperkalaemia were detected using a multiple logistic regression model. Subsequently, the velocity during a defined observation period was compared between patients with one risk factor and patients with two or more risk factors. Finally, the dose effects of drugs identified as risk factors for a high velocity of the development of hyperkalaemia were analysed using two sample comparisons., Results: A random sample of 551 hospitalised patients was analysed. Compared with the drug treatment at entry, significantly more patients during the hospitalisation were treated with drugs associated with hyperkalaemia, such as heparins (p<0.001), ACE inhibitors or angiotensin receptor blockers (ARBs) [p=0.002], potassium supplements (p<0.001), potassium-sparing diuretics (p<0.001) and/or NSAIDs or selective cyclo-oxygenase (COX)-2 inhibitors (p<0.001). Risk factors associated with a high velocity of the development of hyperkalaemia were use of potassium supplements (adjusted odds ratio [OR] 3.386; 95% CI 2.251, 5.091), severe renal impairment (OR 3.119; 95% CI 2.007, 4.850), use of ACE inhibitors or ARBs (OR 2.642; 95% CI 1.742, 4.006), use of potassium-sparing diuretics (OR 2.065; 95% CI 1.310, 3.254), and diabetes mellitus (OR 1.525; 95% CI 1.005, 2.313). The velocity of the development of hyperkalaemia significantly increased in patients with two or more risk factors. Dose effects could be found for potassium supplements (p=0.006) and potassium-sparing diuretics (p=0.007), but not for ACE inhibitors or ARBs (p=0.289). In contrast, the use of kaliuretics (loop diuretics or thiazides) was associated with a decreased velocity of the development of hyperkalaemia in patients with serious renal impairment (p=0.016) and in patients treated with two or more drug classes associated with a high velocity of the development of hyperkalaemia (p=0.001)., Conclusions: Risk factors associated with a high velocity of the development of hyperkalaemia are use of potassium supplements>severe renal impairment>use of ACE inhibitors or ARBs>use of potassium-sparing diuretics>diabetes mellitus. The presence of two or more of these risk factors is associated with an even faster development of hyperkalaemia. Clinicians should be aware of these risk factors in order to avoid a rapid development of potentially life-threatening hyperkalaemia.