10 tips on how to manage severe arrhythmia in haemodialysis patients

Authors: Eleni Stamellou, Christos Georgopoulos, Lampros Lakkas, Evangelia Dounousi

Abstract

Cardiovascular disease, particularly life-threatening ventricular arrhythmias and sudden cardiac death (SCD), remains the leading cause of death among haemodialysis (HD) patients, with an alarmingly higher incidence compared with the general population. By addressing key risk factors such as electrolyte imbalances, fluid overload and ultrafiltration rates, focusing on practical interventions and incorporating multidisciplinary care, clinicians can significantly reduce the risk of fatal arrhythmias. Here we propose 10 practical tips to guide clinicians in managing severe arrhythmias in HD patients. Each tip provides actionable insights for identifying high-risk individuals, with an emphasis on prevention and multidisciplinary care.

INTRODUCTION

Cardiovascular disease is the leading cause of death among haemodialysis (HD) patients, accounting for ≈50% of deaths [1]. The majority of these deaths are due to arrhythmic events or sudden cardiac death (SCD) [1–3]. The aetiology of SCD in this group is not fully understood, underscoring the critical need to investigate how HD may contribute to fatal arrhythmias, their frequency and the terminal rhythms involved [4]. Three different types of SCD seem to appear in different timeframes in HD patients. The SCD that appears at the end of the long interdialytic interval, typically before the first dialysis session of the week, is associated with fluid overload, electrolyte imbalances (particularly hyperkalaemia) and metabolic acidosis that accumulate over the extended break [5–7]. The second type of SCD appears during the first short interdialytic interval, often within 12 hours after the first dialysis session of the week, and is related to rapid electrolyte shifts, particularly a sudden decrease in potassium levels, and haemodynamic changes induced by the dialysis procedure [6, 8]. Lastly, it is crucial to differentiate SCD occurring outside of HD sessions from intradialytic sudden cardiac arrest (SCA), which occurs during the dialysis session and is associated with factors specific to the dialysis procedure, such as rapid ultrafiltration, exposure to low-potassium or low-calcium dialysate and dialysis-induced myocardial stunning [7, 8].

Early studies using standard ECG and ambulatory monitoring had limited ability to capture temporal and circadian arrhythmia patterns, leading to inconsistent findings. More recent studies employing implantable loop recorders have clarified the types of arrhythmias associated with SCD in HD patients. These studies have revealed that bradyarrhythmias, rather than tachyarrhythmias, are the predominant severe arrhythmias in this population [9–14]. Notably, the Monitoring in Dialysis (NCT01779856) study found that two-thirds of participants experienced at least one arrhythmic event, with bradyarrhythmias and asystole occurring more frequently than ventricular arrhythmias [9].

Here we propose 10 practical tips to guide clinicians in managing severe arrhythmias in HD patients (Fig. 1). Each tip offers actionable insights for identifying high-risk individuals, with an emphasis on prevention and multidisciplinary care.

TIP ACUTE MANAGEMENT

When confronted with an acute arrhythmic event in HD patients, the first step is to rapidly assess for signs of clinical instability. These include hypotension, shortness of breath, chest pain or a decreased level of consciousness (Fig. 2). If the patient is unstable or pulseless, management should follow adult advanced cardiac life support (ACLS) protocols. This includes ensuring airway and breathing if needed, commencing cardiopulmonary resuscitation and attaching a defibrillator to assess the rhythm, acting according to ACLS protocols [15]. However, if the patient is haemodynamically stable, a more methodical approach is warranted. This includes a detailed examination of the 12-lead electrocardiogram (ECG), which can identify the arrhythmia in ≈80% of cases. Treatment decisions for tachyarrhythmias should be guided by the width, morphology and regularity of the QRS complex.

When managing acute emergencies in dialysis patients, adherence to the universal ACLS algorithm is essential. Personnel in the HD unit must be adequately trained to recognize and respond to acute events, as initiating cardiopulmonary resuscitation by trained HD staff triples survival odds and improves neurologic outcomes after cardiac arrest [16]. A trained dialysis nurse should operate the HD machine, promptly stopping dialysis and returning the patient's blood volume with a fluid bolus. The patient should be disconnected from the dialysis machine (unless it is defibrillation-proof) in accordance with International Electrotechnical Committee standards, while keeping the dialysis access open for drug administration [17].

TIP IDENTIFY RISK FACTORS

In HD patients, several risk factors significantly increase the likelihood of both bradyarrhythmias and tachyarrhythmias. These include potential structural, anatomical and functional cardiac abnormalities. Evaluation should begin with a thorough patient history, focusing on symptoms, risk factors and any prior cardiovascular conditions. For structural causes, consider ischaemic heart disease, as previous myocardial infarctions can lead to scar tissue formation, disrupting electrical conduction. Imaging, like echocardiography, can help assess heart size, function and valve integrity, which may point to valvular disease. Evaluate for heart failure by assessing left ventricular function and signs of fluid overload. Functional causes, such as autonomic imbalances or electrolyte disturbances, should also be considered. In this high-risk population, additional uraemia-related and dialysis-specific risk factors predisposing to severe arrhythmias are fluctuations in electrolytes and pH, accumulation of uraemic toxins, high ultrafiltration rates, dialysate temperature, oscillations in blood pressure, anaemia and chronic inflammation (Table 1) [9].

Specific risk factors for bradyarrhythmias include age >55 years, coronary artery disease, a prolonged PR interval, diabetes mellitus and long interdialytic intervals [11]. Specific risk factors for tachyarrhythmias include age >55 years, heart failure, left ventricular hypertrophy, history of hypertension and coronary artery disease [9, 18]. Risk factors of SCD include potassium imbalance [19, 20], dialysate composition [21, 22], dialysis modality [23], autonomic hyperactivity and the timing of dialysis sessions.

As mentioned above, autonomic dysfunction is a critical factor in the pathogenesis of cardiac arrhythmias and SCD [24, 25]. In patients with CKD, this entity is characterized by heightened sympathetic activity and diminished parasympathetic tone, resulting in a pro-arrhythmic environment [26, 27]. This dysfunction is particularly prevalent in dialysis patients, where it significantly increases the risk of arrhythmias [28] and the frequency of arrhythmias during dialysis sessions [29]. The association between autonomic dysfunction and adverse cardiovascular outcomes underscores the importance of monitoring these patients closely. To diagnose autonomic dysfunction in dialysis patients, several specific tests are utilized that assess the integrity and function of the autonomic nervous system, including heart rate variability, Belavere's score, tilt table test and Valsalva manoeuvre [30, 31]. Despite advancements in evaluating autonomic nervous system function, challenges remain due to the lack of standardized protocols and consensus tools. This limitation hampers the accuracy and clinical utility of assessments aimed at identifying autonomic dysfunction in this high-risk population.

TIP DRUG-INDUCED ARRHYTHMIAS

Many commonly used medications can induce or exacerbate a variety of arrhythmias [32]. Awareness of this possibility and of the drugs that may trigger arrhythmias represents the first step of prevention. Management of drug-induced arrhythmias includes prompt discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Drugs that may impair the sinus node or atrioventricular (AV) node function can lead to bradycardia or even sinus arrest. Such medications should be avoided in patients with pre-existing sinus or AV dysfunction, unless a functioning pacemaker is in place (Table 2) [32]. Occasionally, ventricular arrhythmias may be triggered by medications, particularly anti-arrhythmic drugs with pro-arrhythmic effects, especially class I and II agents, stimulants such as caffeine, nicotine, cocaine and amphetamines or QT-prolonging drugs (Table 3).

TIP 4: MANAGEMENT AND PREVENTION OF QT PROLONGATION

QT prolongation is an independent predictor of mortality in patients with kidney failure, strongly associated with all-cause mortality and SCD [33]. In males, a borderline QTc is defined as ranging from 431 to 450 msec, while in females this range extends from 451 to 470 msec. A QTc value >450 msec in males and >470 msec in females is classified as abnormal.

Multiple mechanisms contribute to QT prolongation in dialysis patients, primarily driven by the unique metabolic and fluid shifts associated with kidney failure and HD electrolyte disturbances, particularly fluctuations in potassium and calcium; uraemia-induced myocardial dysfunction, as uraemic toxins affect cardiac ion channel function, directly extending the QT interval; rapid ultrafiltration causing haemodynamic stress and destabilization of the myocardium; autonomic dysfunction, with suppressed parasympathetic activity and increased sympathetic activity, impairing the heart's ability to adapt to volume and pressure changes during HD; and co-medications that are known to prolong the QT interval (Table 3) [33, 34].

Managing QT prolongation involves careful monitoring of serum electrolytes before, during and after HD to prevent abrupt shifts in potassium and calcium that could exacerbate the condition (Fig. 1) [35, 36]. A thorough review of the patient's medications, as mentioned above, is necessary to identify and substitute drugs that prolong the QT interval. For essential drugs that have this side effect, increased vigilance with ECG monitoring and careful electrolyte management is required. In cases of significant QT prolongation where the risk of fatal arrhythmias is high, an implantable cardioverter-defibrillator (ICD) may be considered [37].

TIP MONITOR POTASSIUM LEVELS

Approximately 85% of potassium clearance during an HD session is attributed to diffusion, driven by the gradient between blood and dialysate potassium levels. As this gradient narrows, potassium removal decelerates. The most significant decrease occurs within the first hour, ≈1 mEq/l, then continues to decrease by an additional 1 mEq/l over the subsequent hours. Potassium levels tend to stabilize in the final hour as the rate of removal aligns with re-equilibration [38].

There is no consensus on the ideal dialysate potassium concentration, leading to wide variations in its prescription worldwide. Evidence suggests an elevated risk of SCD associated with very low dialysate potassium (i.e. 1 mEq/l) in patients whose pre-dialysis serum potassium levels are low to normal. Although long-term studies are sparse, several short-term studies using cardiac monitoring devices have observed a higher incidence of certain heart rhythm abnormalities with low-potassium dialysate [39]. However, it is essential, to recognize that no study has shown a significant risk associated with a low-potassium dialysate (i.e. 2 mEq/l) in patients with higher serum potassium levels before dialysis [40].

Based on data from the Dialysis Outcomes and Practice Patterns Study, the optimal pre-dialysis potassium range for HD patients is 4–5.5 mEq/l. Levels >5.6 mEq/l are linked to an increased risk of cardiac death and arrhythmias [41]. Below are some practical tips on prescribing potassium in dialysate (Fig. 1).

• Consider other factors that influence potassium removal during HD:
• High-glucose promotes intracellular potassium shifting, leading to a rapid decrease in serum potassium, especially in the first hour.
• High-bicarbonate increases potassium uptake by cells, accelerating the initial decline in serum potassium, although the total amount of potassium removed remains unchanged.
• ‘Rule of seven’: a commonly used guideline for determining the appropriate dialysate potassium concentration in HD patients. This rule aims to maintain a balance between removing excess potassium and preventing dangerous fluctuations in serum potassium levels during and after dialysis [20]. This rule suggests setting the dialysate potassium concentration by subtracting the pre-dialysis serum potassium from seven. This formula helps tailor the dialysate concentration to individual patient needs [40].
• Avoid dialysate potassium <2 or >3  mEq/l [39]. The use of a dialysate potassium concentration >3 mEq/l (such as 4 mEq/l) may be appropriate in patients with low pre-dialysis serum potassium (<3.5 mEq/l). However, they should be used judiciously and require regular monitoring of pre-dialysis serum potassium to ensure it remains appropriate for the patient's current condition.
• Regularly review and adjust the dialysate potassium especially important after hospitalizations or acute changes, monitor pre-dialysis serum potassium levels to make necessary adjustments.
• Potassium involves starting with a relatively high dialysate potassium concentration and gradually reducing it throughout the session. This approach slows the decrease in potassium during the first hours of dialysis but achieves the same total potassium removal as a traditional session [42].
• Use potassium binders. A recent study found that using a higher dialysate potassium concentration (3.0 mmol/l) combined with sodium zirconium cyclosilicate (SZC) reduced the incidence of arrhythmias compared with a lower dialysate potassium (2.0 mmol/l) without SZC [43]. The use of potassium binders may also help mitigate the risk of post-dialytic hypokalaemia, which is associated with increased arrhythmia risk [44]. A mortality advantage was also discovered in a large registry study where patients using potassium binders (sodium or calcium polystyrene sulphonate) at doses of 4–8 g/day or ≥8 g/day had a lower mortality risk compared with those not using binders [44]. However, it is important to note that these associations may be influenced by other factors, such as dietary habits, and more research is needed to confirm a direct causal relationship between potassium binder use and improved survival.

TIP MONITOR CALCIUM AND MAGNESIUM LEVELS

In HD, the ionized calcium level in the blood is directly influenced by the concentration of calcium in the dialysate. It has been demonstrated that fluctuations in blood calcium levels during dialysis can significantly affect blood pressure, myocardial contractility and vascular reactivity and can even contribute to QT interval prolongation [8].

In recent years, the standard calcium concentration in dialysate has been reduced from 1.75 to 1.25 mmol/l. Although this lower calcium concentration in the dialysate can help prevent hypercalcaemia and vascular calcifications, it also has the potential to increase myocardial repolarization time, prolong the QT interval and elevate the risk of cardiac arrhythmias and SCD [34].

Customizing the dialysate calcium concentration requires a balance between bone mineral metabolism and cardiovascular health. Patients with pre-existing QT prolongation or cardiovascular disease should avoid low-calcium dialysate (1.25 mmol/l), especially when combined with low-potassium dialysate, due to the increased risk of arrhythmias (Fig. 1). In high-risk populations, consider using a dialysate calcium concentration that increases serum calcium near the upper limit of the normal range [45].

Magnesium levels are a significant risk factor for arrhythmias. There seems to be an inverse association between serum magnesium levels and the risk of sudden cardiac death in HD patients. In a post hoc analysis of the CONTRAST trial (NCT00205556), a 0.1 mmol/l increase in serum magnesium decreased the hazard ratio (HR) for sudden cardiac death by 24% [HR 0.76 (95% confidence interval 0.62–0.93)] [46].

In patients with kidney failure, serum magnesium tends to be elevated due to reduced kidney function, dietary intake, medications and dialytic clearance. During HD, only part of the magnesium is available for clearance due to its binding to proteins and other ions. Both high and low magnesium levels are associated with adverse outcomes, including arrhythmias [47].

Previously, concerns about osteomalacia and reports of improved uraemic pruritus with lower magnesium dialysate led to decreased magnesium prescriptions. However, the recognition of higher magnesium levels in preventing arterial calcification has led most manufacturers to standardize dialysate magnesium concentrations at 0.5 mmol/l (1.0 mEq/l).

Given the high prevalence of hypomagnesemia, its associated mortality risk and its role in stabilizing potassium levels, it is advisable to prescribe a higher concentration of magnesium dialysate (0.5 mmol/l or 1.0 mEq/l) (Fig. 1). This recommendation is particularly targeted at hypokalaemic patients or those experiencing significant potassium fluctuations. In cases of hypermagnesemia, clinicians should evaluate dietary factors and medications that might contribute to elevated magnesium levels [49].

TIP OPTIMIZE FLUID BALANCE

Ultrafiltration volumes >5.7% of body weight or ultrafiltration rates >13 ml/kg/h are associated with an increased risk of cardiovascular events and SCD [49]. Persistent fluid overload is associated with an increased risk of death in HD patients [50]. Furthermore, rates of cardiovascular death and hospitalization are higher on HD days compared with non-HD days, with a noticeable peak during the longer 2-day interval. This pattern is similarly observed for SCD, emphasizing a temporal association with HD therapy [51].

Below are some practical tips on how to manage interdialytic weight gain (Fig. 1):

• Regular evaluation of dry target Regularly assess the prescribed dry target weight. Determining the ‘ideal’ target weight often involves a trial-and-error approach, aiming to set the target body weight just above the threshold where undesirable symptoms (e.g. cramping, nausea, vomiting or hypotension) manifest. To enhance the precision of clinical target weight estimation, validated, advanced methods such as blood volume monitoring, lung ultrasound and bioimpedance are recommended, especially for patients requiring ultrafiltration rates >10 ml/min/h [52, 53].
• Sodium intake Limit sodium intake to 1–2 g/day between dialysis sessions to minimize excessive interdialytic volume gains and reduce the need for aggressive ultrafiltration [54].
• Dialysate sodium composition Adjust the sodium concentration in the dialysate to lower levels to reduce interdialytic weight gain and improve blood pressure control [55]. In some patients, this should be personalized by evaluating the patient's pre-dialytic sodium levels. Avoid high fixed sodium concentrations (>140 mEq/l) in the dialysate, or sodium modelling, as these practices have been linked to increased weight gain and elevated blood pressure in both controlled and observational studies [54].
• Increase dialysis Consider increasing the frequency of dialysis sessions from three to four times per week if volume overload is unmanageable within the standard three-session regimen. There is evidence from echocardiographic and pulse wave velocity studies showing greater increases in central haemodynamic parameters and left ventricular workload during the long interval compared with the regular 2-day interval. The long interval is associated with greater increases in left and right atrial volumes, indicating more significant cardiac stretching [56]. These physiological changes during the long interdialytic interval translate into higher rates of all-cause mortality and cardiovascular-related mortality on the day following the long interval [57, 58].
• Exploration of alternative dialysis If managing volume overload continues to be a challenge, consider switching to alternative dialysis modes such as haemodiafiltration, daily dialysis or nocturnal HD.

TIP ASSESS DIALYSATE BICARBONATE (DBIC)

DBIC is crucial for correcting metabolic acidosis in HD patients. However, elevated DBIC concentrations can lead to rapid changes in serum electrolytes, notably potassium and calcium, predisposing patients to arrhythmias [59]. Correction of metabolic acidosis promotes the intracellular shift of potassium, thereby lowering extracellular potassium levels. Similarly, increased serum bicarbonate can reduce serum calcium through protein-binding effects. These shifts may prolong the QT interval, especially when DBIC is combined with low-calcium or low-potassium dialysates, thus increasing the risk for life-threatening ventricular arrhythmias.

It is advisable to avoid using low-calcium and low-potassium dialysate in combination with high DBIC concentrations, particularly in patients with a prolonged baseline QT interval (Fig. 1). This combination increases the risk of dangerous QT prolongation and ventricular arrhythmias. For patients with known cardiovascular risks, such as those on beta-blockers or those already exhibiting a prolonged QT interval, it is crucial to carefully adjust DBIC levels and consider using higher potassium and calcium concentrations in the dialysate [60]. A randomized controlled trial found that higher DBIC concentrations are associated with a faster decrease in intradialysis plasma potassium concentrations [60].

In summary, the ideal pre- and post-dialysis plasma bicarbonate concentration should range between 24 and 28 mmol/l, although most patients have a pre-HD plasma concertation of 19–22 mmol/l after the long interval between HD sessions. The dialysate DBIC should not exceed 35 mmol/l (Fig. 1) [55].

TIP CARDIOLOGY REFERRAL

Cardiology referral of high-risk HD patients is of paramount importance. Recent findings from implantable loop recorders have shed light on the mechanisms of SCD and severe arrythmias in this population [11–14, 18], identifying risk factors for both conditions [18]:

• Cardiac structural left ventricular hypertrophy and coronary artery disease.
• Diabetes: diabetic patients seem to be at a higher risk, even with preserved ejection fraction.
• Sleep obstructive sleep apnoea is associated with an increased SCD risk in HD patients.
• Severe aortic HD patients with untreated severe aortic stenosis are at particularly high risk.
• Autonomic impaired heart rate variability is common in HD patients and may contribute to arrhythmia risk.
• Timing of increased risk at the end of the long interdialytic interval.
• Electrolyte imbalances as discussed above in Tips 4–6.
• Rapid ultrafiltration as discussed in Tip 7 [61].

Arrhythmia prevention and management in HD patients requires careful selection of cardioprotective medications. In particular, in HD patients with heart failure with reduced ejection fraction (HFrEF), beta-blockers and renin–angiotensin–aldosterone system inhibitors are commonly recommended, although evidence supporting these drug categories in HFrEF patients on dialysis is largely indirect, as this group is typically excluded from HFrEF trials. Beta-blockers have been shown to significantly reduce all-cause mortality and cardiovascular events in dialysis patients [62, 63]. However, the optimal choice of beta-blocker remains uncertain due to variability in cardioselectivity and dialysability [64, 65]. While mineralocorticoid receptor antagonists and sodium–glucose co-transporter 2 inhibitors have demonstrated significant cardiovascular benefits in non-HD CKD patients and could theoretically benefit HFrEF patients on HD, they are currently not recommended and generally avoided due to risks of hyperkalaemia and limited safety and effectiveness data.

Non-pharmacological interventions for arrhythmia management in HD patients follow similar indications to those in the general population but require special

• Pacemaker: In HD patients, considerations include increased infection risk due to immune compromise and frequent vascular access, as well as potential interference with pacemaker function from rapid electrolyte shifts during dialysis. Moreover, pacemaker leads in central veins may impact future vascular access options. Adjustments may be necessary to prevent interference from dialysis machines [66].
• ICD: The American College of Cardiology/American Heart Association and the European Society of Cardiology guidelines recommend that dialysis patients who have survived SCD receive standard treatment, including the use of ICDs for secondary prevention [67]. Managing device-related complications and interactions with dialysis is critical [68]. Nevertheless, there are a number of studies that have evaluated the effectiveness of ICD in dialysis patients and have yielded inconclusive results [69–72]. The effectiveness of ICDs is decreased in advanced CKD, likely due to competing pathophysiological factors such as non-shockable arrhythmias, higher defibrillation threshold, myocardial scarring, coexisting atrial fibrillation, lower use of guideline-directed medical therapy and non-arrhythmic mortality [73], although ICD implantation in cardiac arrest survivors on dialysis is associated with greater survival [69]. The only randomized trial that exists on this issue confirms that prophylactic ICD therapy did not reduce the rate of SCD or all-cause mortality (which remained high) in dialysis patients [74].

TIP EDUCATING PATIENTS ON SYMPTOMS TREATMENTS, DIET AND NUTRITION

Educating patients on dialysis about the potential risks of arrhythmias is crucial, especially concerning hyperkalaemia. They need to recognize symptoms such as muscle weakness, numbness, tingling or unexplained fatigue, which require timely medical intervention. Additionally, they should be aware of arrhythmia indicators like palpitations, dizziness, chest discomfort and breathlessness, which signal high cardiovascular risk.

Educating patients on lifestyle modifications can significantly reduce these risks. To prevent rapid fluid removal during dialysis, patients should limit their sodium and fluid intake. Those with minimal residual kidney function must strictly control fluid intake to prevent overload, while those with residual kidney function should monitor their urine output to ensure it remains within safe limits. Potassium intake should not exceed 60 mEq/day, aiming for pre-dialysis potassium levels of 4.0–5.5 mEq/l.

By adhering to these dietary guidelines and understanding the impact of lifestyle choices, patients can proactively manage their condition, reduce the risk of severe arrhythmia risks and enhance their overall quality of life.

CONCLUSION

HD patients suffer from a disproportionately high burden of cardiovascular morbidity and mortality, with almost 30–40% of deaths being attributed to severe arrhythmias and SCD. The risk factors and mechanisms of arrhythmias in this high-risk population are multiple and complex, implicating electrolyte and pH imbalances (potassium, calcium and magnesium), fluid and blood pressure fluctuations, uraemic milieu and autonomic dysfunction. Dialysis-related factors, including the dialysis modality and treatment schedule (ultrafiltration rates, dialysate temperature and bicarbonate), as well as polypharmacy and altered pharmacokinetics in HD further contribute to arrhythmogenesis. Early identification of high-risk patients, monitoring and control of risk factors and individualized pharmacological interventions are vital key points in order to reduce the incidence of severe arrhythmias. Furthermore, increased awareness, patient education and a multidisciplinary approach involving nephrologists, cardiologists and dialysis staff are critical to improve outcomes. Although there have been advances in acute and long-term management, further research is needed to develop more effective preventive and therapeutic approaches customized to this high-risk population.