The impact of serum potassium‐influencing antihypertensive drugs on the risk of out‐of‐hospital cardiac arrest: A case–control study

Alharbi, Fawaz; Souverein, Patrick C.; Groot, Mark de; Blom, Marieke T.; Boer, Anthonius de; Klungel, Olaf H.; Tan, Hanno L.

doi:10.1111/bcp.13356

Cited by 7 publications

(6 citation statements)

References 33 publications

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“…Indeed, hypokalemia induces conduction abnormalities, such as increased P wave amplitude and duration, a slight prolongation of the PR interval, atrioventricular block, increased QRS duration, and cardiac arrest . We found all of these electrocardiographic conduction disturbances in our experimental hypokalemia model (Figures ).…”

Section: Discussionsupporting

confidence: 54%

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

Prado

Beňová

Diez

et al. 2019

Journal of Pineal Research

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Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium-induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin-43 preservation. After stabilization in Krebs-Henseleit solution (4.5 mEq/L K + ), isolated hearts from Wistar rats underwent perfusion with low-potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation.Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin-43 were examined. Melatonin reduced the incidence of low potassium-induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin-43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin-43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium-induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin-43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent. K E Y W O R D Saction potential, arrhythmias, connexin-43, hypokalemia, melatonin, QRS

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Section: Discussionsupporting

confidence: 54%

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

Prado

Beňová

Diez

et al. 2019

Journal of Pineal Research

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“…However, in this study, our patients with elevated potassium levels had one or more conditions causing hyperkalemia such as comorbid HTN, DM, or CKD, and high rates of certain medications use, including non-steroidal anti-inflammatory drugs (NSAIDs) beta-blockers, CCBs, ACEIs, and ARBs. These findings are concordant with previous reports on the risk factors of hyperkalemia [6,14,15,[47][48][49][50][51][52][53]. Our study as well reported high rates of statins and PPIs to use within hyperkalemic patients.…”

Section: Discussionsupporting

confidence: 93%

Clinical and electrocardiogram presentations of patients with high serum potassium concentrations within emergency settings: a prospective study

et al. 2022

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Background Elevated potassium level is a common and reversible peri-arrest condition. Diagnosis and management of hyperkalemia in a short time is critical, where electrocardiogram (ECG) alterations might be helpful. We aimed to investigate the role of clinical features and ECGs in early diagnosing and treating hyperkalemia. Methods Prospectively, adult patients who presented to the emergency department (ED) from July 2019 to March 2020 with hyperkalemia (serum potassium ≥5.5mmol/L) were included. History was obtained, and laboratory investigations and ECGs were performed at the presentation and before initiating hyperkalemia therapy. Hyperkalemia severity was divided into mild (5.5–5.9mmol/L), moderate (6.0–6.4mmol/L), and severe (≥6.5mmol/L). A cardiologist and emergency physician blinded to laboratory values, study design, and patients’ diagnoses interpreted ECGs and presenting symptoms independently to predict hyperkalemia. Results Sixty-seven hyperkalemic patients with a mean (±SD) serum potassium level of 6.5±0.7mmol/L were included in this study. The mean age was 63.9±15.1, and 58.2% were females. Hyperkalemia was mild in 10.4%, moderate in 40.3%, and severe in 49.3%. Almost two thirds of patients (71.6%) had hypertension, 67.2% diabetes, and 64.2% chronic kidney disease. About one-quarter of patients (22.4%) were asymptomatic, while fatigue (46.3%), dyspnea (28.4%), and nausea/vomiting (20.9%) were the most common presenting symptoms. Normal ECGs were observed in 25.4% of patients, while alterations in 74.6%. Atrial fibrillation (13.4%), peaked T wave (11.9%), widened QRS (11.9%), prolonged PR interval (10.5%), and flattening P wave (10.5%) were the most common. Peaked T wave was significantly more common in severe hyperkalemia (87.5%) than in mild and moderate hyperkalemia (12.5%, 0.0%, respectively) (p=0.041). The physicians’ sensitivities for predicting hyperkalemia were 35.8% and 28.4%, improved to 51.5% and 42.4%, respectively, when limiting the analyses to severe hyperkalemia. The mean (±SD) time to initial hyperkalemia treatment was 63.8±31.5 min. Potassium levels were positively correlated with PR interval (r=0.283, p=0.038), QRS duration (r=0.361, p=0.003), peaked T wave (r=0.242, p=0.041), and serum levels of creatinine (r=0.347, p=0.004), BUN (r=0.312, p=0.008), and CK (r=0.373, p=0.039). Conclusions The physicians’ abilities to predict hyperkalemia based on ECG and symptoms were poor. ECG could not be solely relied on, and serum potassium tests should be conducted for accurate diagnosis.

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“…With respect to non-potassium-sparing diuretics, we observed a 1.4-fold increased CVM in the meta-analysis of the results from the two studies. This is in line with the results of Cooper et al [21] (population: patients with left ventricular dysfunction; outcome: arrhythmic death), Ahmed et al [20] (population: heart failure patients; outcome: long-term mortality), and Alharbi et al [40] (population: cases with cardiac arrest and controls from the general population; outcome: cardiac arrest). However, our results are not directly comparable to these studies because we included a population with a lower cardiovascular risk (e.g., a mix of patients with hypertension and/or heart failure receiving antihypertensive drugs).…”

Section: Discussionsupporting

confidence: 90%

The Associations of Diuretics and Laxatives Use with Cardiovascular Mortality. An Individual Patient-Data Meta-analysis of Two Large Cohort Studies

Hoppe

Muhlack

Köenig

et al. 2019

Cardiovasc Drugs Ther

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PurposeTo investigate the associations of diuretics overall, non-potassium-sparing diuretics in specific, and laxative use with cardiovascular mortality (CVM) in subjects with antihypertensive treatment.MethodsAnalyses included 4253 participants, aged 50 to 75 years, from the German ESTHER cohort and 105,359 participants, aged 50 to 69 years, from the UK Biobank. Cox proportional hazard regression models were applied in both studies, and then results were pooled using random-effects model meta-analyses.ResultsDuring 14 and 7 years of follow-up, 476 and 1616 CVM cases were observed in the ESTHER study and the UK Biobank, respectively. Compared to non-users, a 1.6-fold (hazard ratio [95% confidence interval] 1.57 [1.29; 1.90]), a 1.4-fold (1.39 [1.26; 1.53]), and no statistically significantly increased (1.13 [0.94; 1.36]) CVM were observed in users of diuretics overall, non-potassium-sparing diuretics in specific, and laxatives, respectively. Concurrent use of non-potassium-sparing diuretics and laxatives was associated with a 2-fold increased CVM (2.05 [1.55; 2.71]) when compared to users of neither diuretics nor laxatives. However, a test for interaction slightly missed statistical significance (p = 0.075).ConclusionsThese consistent results from two large cohort studies imply that more research is needed on the safety of diuretics in routine care. Although not statistically significant in this study, a drug-drug interaction of non-potassium-sparing diuretics and laxatives appears plausible. Physicians and pharmacists are advised to clarify additional laxative use in users of non-potassium-sparing diuretics and inform about the risk of concurrent use. Moreover, closer potassium monitoring intervals (e.g., every 3 months) might be indicated in concurrent users to prevent fatal cardiovascular events.Electronic supplementary materialThe online version of this article (10.1007/s10557-019-06894-w) contains supplementary material, which is available to authorized users.

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The impact of serum potassium‐influencing antihypertensive drugs on the risk of out‐of‐hospital cardiac arrest: A case–control study

Abstract: The risk of OHCA is significantly increased in patients who were current users of hypokalaemia-inducing antihypertensives and patients using a combination of antihypertensives with hypo- and hyperkalaemic effects.

Cited by 7 publications

References 33 publications

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

Clinical and electrocardiogram presentations of patients with high serum potassium concentrations within emergency settings: a prospective study

The Associations of Diuretics and Laxatives Use with Cardiovascular Mortality. An Individual Patient-Data Meta-analysis of Two Large Cohort Studies

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