Hyperkalemia: A Clinical Review

Written By Danial Mirza

Definition

Hyperkalemia is an electrolyte disturbance defined as a serum or plasma potassium level above the upper limit of the normal range. The adoption of a standardized definition is not merely academic; it is a cornerstone of patient safety. In a busy healthcare system like Malaysia's, where patients move between primary care clinics (Klinik Kesihatan), district hospitals, and tertiary referral centers, a shared clinical language is critical. According to the 2024 Malaysian Consensus on the Management of Acute & Persistent Hyperkalaemia, hyperkalemia is specifically classified by severity to standardize risk stratification, clinical communication, and management protocols across all healthcare levels (9). This ensures that a house officer's report of "moderate hyperkalemia" is understood with the same degree of urgency by a senior consultant miles away.

  • Mild Hyperkalemia: 5.5 - 5.9 mmol/L

  • Moderate Hyperkalemia: 6.0 - 6.4 mmol/L

  • Severe Hyperkalemia: ≥ 6.5 mmol/L

Epidemiology

In Malaysia, hyperkalemia represents a significant and growing clinical burden, largely driven by the "twin epidemics" of Chronic Kidney Disease (CKD) and Type 2 Diabetes Mellitus (T2DM) (7, 9). Local data highlights the gravity of the issue; a retrospective study at a Malaysian hospital found that hyperkalemia (K+ ≥ 5.5 mmol/L) occurred in a staggering 54.5% of deceased patients with T2DM, with advanced CKD being a major determinant (27). This creates a "perfect storm" scenario: a large patient population with impaired renal potassium excretion who simultaneously require life-saving medications that increase potassium levels.

The risk is amplified by the essential use of Renin-Angiotensin-Aldosterone System inhibitors (RAASi) like ACE inhibitors and ARBs. These drugs are the cornerstone of guideline-directed medical therapy for reducing mortality in heart failure and slowing the progression of diabetic nephropathy, yet they are a leading iatrogenic cause of hyperkalemia (6). This frequent clinical challenge contrasts sharply with a prevalence of less than 5% in the general global population. The prevalence rises to 10% in hospitalized patients and can be as high as 73% in patients with advanced CKD, illustrating that hyperkalemia is predominantly a disease of patients with significant underlying comorbidities (4, 6).

Pathophysiology

Potassium homeostasis is a dynamic process maintained by a delicate balance between external excretion (primarily renal) and internal distribution between the vast intracellular fluid (ICF) and the small extracellular fluid (ECF) compartments (3). Hyperkalemia arises from three core mechanisms: decreased renal excretion, a transcellular shift of potassium from the ICF to the ECF, or excessive potassium intake, which is rarely a cause in isolation but often a precipitant in patients with impaired excretion (2).

The cardiotoxicity of hyperkalemia is a direct result of its effect on the cardiac myocyte resting membrane potential, which is determined by the ratio of intracellular to extracellular potassium. Elevated extracellular potassium reduces this ratio, making the resting potential less negative (partially depolarized). Initially, this depolarization brings the membrane closer to its firing threshold, increasing myocardial excitability. This is thought to cause the earliest ECG change—tall, "tented" T-waves—by accelerating ventricular repolarization through its effect on potassium channels (1, 21).

However, as hyperkalemia worsens, this sustained depolarization leads to the inactivation of voltage-gated sodium channels. These channels are responsible for the rapid upstroke (Phase 0) of the cardiac action potential. Their inactivation dramatically slows cardiac impulse conduction. This electrophysiological slowing manifests on the ECG as PR interval prolongation (delayed AV nodal conduction), widening of the QRS complex (delayed intraventricular conduction), and eventually, the development of sine-wave patterns, ventricular fibrillation, or asystole (1, 21).

Clinical Presentation

A critical and dangerous feature of hyperkalemia is that it is often clinically "silent," especially when mild or developing slowly, and is frequently an incidental laboratory finding (5). The absence of symptoms provides a false sense of security and does not reduce the risk of sudden, fatal cardiac events. When symptoms do occur, they are typically non-specific, related to impaired neuromuscular function, and usually manifest at higher potassium levels (>6.5 mmol/L) or with a rapid rate of rise.

  • Diagnostic Clues: The presence of any hyperkalemic ECG changes is a pathognomonic sign of significant cardiotoxicity and a true medical emergency.

  • Common Symptoms (>50%): Generalized fatigue, muscle weakness, and malaise are the most common but are too non-specific to be reliable diagnostic indicators on their own (5).

  • Less Common Symptoms (10-50%): Paresthesias (numbness or tingling, often in the extremities), muscle cramps, nausea, vomiting, and abdominal pain can occur as hyperkalemia affects both nerve conduction and smooth muscle function (31, 35).

  • ⚠️ Red Flag Signs & Symptoms: Any new ECG abnormality (especially QRS widening), ascending flaccid paralysis that can mimic Guillain-Barré syndrome, or respiratory distress due to diaphragmatic weakness indicates extreme clinical urgency and requires immediate senior medical officer notification and intervention.

Complications

The complications of hyperkalemia are direct extensions of its pathophysiology, affecting all excitable tissues.

  • Cardiovascular: Life-threatening cardiac arrhythmias are the most feared complication. These include ventricular fibrillation, pulseless electrical activity, and asystole. Other manifestations include severe bradycardia and high-degree atrioventricular blocks.

  • Neuromuscular: Severe hyperkalemia can lead to a profound ascending flaccid paralysis. This begins in the lower extremities and progresses upwards. When it involves the muscles of respiration, such as the diaphragm and intercostals, it can cause acute respiratory failure, requiring mechanical ventilation.

  • Gastrointestinal: The effect on gut smooth muscle can lead to paralytic ileus, causing abdominal distension, pain, and vomiting.

Prognosis

The relationship between serum potassium and mortality follows a clear U-shaped curve, with the lowest all-cause mortality risk observed in the narrow range of 4.0 to 5.0 mmol/L (4). Mortality risk begins to climb as potassium deviates from this range and increases sharply once serum potassium exceeds 5.5 mmol/L. It is crucial to understand that this elevated risk is not solely attributable to arrhythmias. An episode of hyperkalemia is an independent marker of severe underlying disease, reflecting the severity of CKD, the degree of heart failure, or the presence of a significant catabolic state. Therefore, even after successful correction, the event itself serves as a prognostic warning sign for future adverse cardiorenal outcomes (6).

Differential Diagnosis

  • Pseudohyperkalemia: This is a crucial differential to exclude before initiating potentially harmful treatment. It is a factitious, in-vitro elevation of potassium caused by hemolysis during a difficult or traumatic blood draw, prolonged tourniquet time, or excessive fist clenching. It can also occur in patients with extreme thrombocytosis (>1,000,000/μL) or leukocytosis (>50,000/μL) due to potassium release during clotting in the sample tube. It is suspected when an unexpectedly high potassium level is reported in a clinically stable patient with a normal ECG. The diagnosis is confirmed by obtaining a repeat sample with careful phlebotomy technique; sending a heparinized plasma sample (green top tube) can also circumvent the issue as it prevents the clotting process that releases potassium from platelets (5, 11).

  • Adrenal Insufficiency (Addison's Disease): Consider this in any patient presenting with the triad of hyperkalemia, hyponatremia, and hypotension. The lack of aldosterone impairs renal potassium excretion. Look for other clues like unexplained weight loss, fatigue, or skin hyperpigmentation (a sign of high ACTH in primary adrenal failure) (20).

  • Rhabdomyolysis: This should be suspected in patients with a history of crush injury, prolonged immobilization, seizures, heat stroke, or the use of certain drugs like statins. The massive release of potassium from destroyed muscle cells causes acute, severe hyperkalemia. It is distinguished by markedly elevated serum creatine kinase (CK) levels, often thousands of units above normal (12).

  • Digitalis Toxicity: This is another important differential, as digoxin inhibits the Na+/K+-ATPase pump, causing potassium to shift out of cells. Patients may present with hyperkalemia, gastrointestinal symptoms, and classic ECG changes (e.g., "scooped" ST segments, arrhythmias) that can confound the diagnosis.

Investigations

Immediate & Bedside Tests

  • 12-lead ECG: This is the mandatory first step for any patient with K+ > 5.5 mmol/L to immediately assess for cardiotoxicity (the action), as ECG changes signal imminent risk of cardiac arrest (the rationale) (9). It is critical to remember the ECG is an insensitive tool; up to 50% of patients with significant hyperkalemia may have a normal ECG. Its role is for risk stratification, not diagnosis (14).

  • Venous/Arterial Blood Gas (VBG/ABG): This provides a rapid point-of-care potassium level for confirmation (the action) and simultaneously assesses for metabolic acidosis, a common contributing cause that also requires correction (the rationale) (34).

  • Point-of-care Blood Glucose: This is essential to screen for Diabetic Ketoacidosis as a cause (the action) and to establish a crucial baseline before administering insulin, a key treatment component that carries a risk of hypoglycemia (the rationale) (34).

Diagnostic Workup

  • First-Line Investigations: An urgent repeat of serum urea, electrolytes, and creatinine is sent to the lab to confirm the diagnosis, rule out lab error or pseudohyperkalemia (the action), and formally assess renal function (eGFR), which is the most common underlying cause of chronic hyperkalemia (the rationale) (13).

  • Gold Standard: While there is no single "gold standard" test for the cause, a comprehensive evaluation including a thorough medication reconciliation, assessment of renal function (eGFR), and targeted tests like serum cortisol (for adrenal insufficiency) or creatine kinase (for rhabdomyolysis) is required to establish the definitive etiology (12, 13).

Monitoring & Staging

  • Serum Creatine Kinase (CK): In cases of suspected muscle injury (e.g., trauma, collapse), a serum CK is crucial to diagnose or rule out rhabdomyolysis (the action), as ongoing muscle breakdown constitutes a massive and continuous potassium load that will overwhelm medical management and likely require dialysis (the rationale) (12).

Management

Management Principles

The management of hyperkalemia is a time-critical, stepwise process focused on three goals: immediate stabilization of the cardiac membrane ("Protect the Heart"), rapid shifting of potassium into cells ("Shift the Potassium"), and definitive removal of potassium from the body ("Remove the Potassium") (9).

Acute Stabilisation (The First Hour)

Emergency treatment is indicated for any patient with K+ > 6.0 mmol/L or any hyperkalemic ECG changes, regardless of the absolute potassium value (9).

  • Cardiac Membrane Stabilisation: Administer 10 mL of 10% Calcium Gluconate IV over 2-5 minutes. This does not lower potassium but directly antagonizes its cardiac effects by restoring the normal electrical gradient across the myocardial cell membrane (the action), thereby protecting the heart from fatal arrhythmias while other treatments take effect (the rationale). This dose can be repeated after 5 minutes if ECG changes persist. Note: Calcium Chloride contains three times more elemental calcium but is more caustic and should ideally be given via a central line to avoid tissue necrosis with extravasation (34).

  • Intracellular Shift (Circulation):

    • Administer a stat bolus of 10 units of short-acting insulin (e.g., Actrapid) IV with 50 mL of 50% Dextrose (D50). This potently stimulates the Na+/K+-ATPase pump (the action), rapidly driving potassium from the blood into cells to lower the serum level within minutes (the rationale). Use with extreme caution in ESRD patients, who have delayed insulin clearance and are at high risk for severe, prolonged hypoglycemia (12).

    • Concurrently, administer 10-20 mg of Salbutamol via nebulizer. This provides an additive potassium-shifting effect through beta-2 adrenergic stimulation (the action), further reducing the immediate risk. It should be used with caution in patients with known ischemic heart disease as the high dose can induce significant tachycardia (the rationale) (18).

Definitive Therapy

  • First-Line Treatment (Removal): For euvolemic or hypervolemic patients with adequate renal function, administer a loop diuretic like IV Furosemide (40-80 mg) to promote kaliuresis (renal potassium excretion) (the action), which is the primary natural route of potassium removal (the rationale). This is ineffective in anuric patients (38).

  • Second-Line/Escalation:

    • Potassium Binders: For acute removal, Sodium Zirconium Cyclosilicate (SZC) at a dose of 10g orally is a valuable tool. It is a highly selective potassium binder with a rapid onset of action (~1 hour) and can be used alongside shifting therapies to bind potassium in the gut (the action), providing a crucial non-renal route of elimination, especially while awaiting dialysis (the rationale) (37).

    • Hemodialysis: This is the most effective and rapid method of potassium removal and is the definitive therapy. It must be urgently considered for patients with severe, refractory hyperkalemia, those with established end-stage renal disease (ESRD), or in cases of hyperkalemic cardiac arrest. Hemodialysis is far superior to peritoneal dialysis for this purpose (11).

Supportive & Symptomatic Care

  • Withhold all potassium-containing IV fluids (e.g., Hartmann's solution) and oral supplements.

  • Perform a meticulous medication reconciliation and discontinue any offending medications known to cause hyperkalemia (e.g., RAASi, NSAIDs, spironolactone, trimethoprim) after discussion with a senior.

  • Provide analgesia or antiemetics as needed for patient comfort.

Key Nursing & Monitoring Instructions

  • Place the patient on continuous cardiac monitoring (telemetry) immediately.

  • Monitor vital signs every 15 minutes for the first hour, then hourly.

  • Check capillary blood glucose every 30-60 minutes for at least 4-6 hours after insulin administration to prevent iatrogenic hypoglycemia.

  • Monitor serum potassium at 1, 2, 4, and 6 hours post-intervention to assess response and detect rebound hyperkalemia.

  • Maintain a strict input/output chart to guide fluid management and assess diuretic response.

  • Inform the medical officer immediately if SBP < 90 mmHg, urine output < 0.5mL/kg/hr, GCS drops, or if any new arrhythmia is detected on the monitor.

Long-Term Plan & Patient Education

The long-term goal is to prevent recurrence while continuing essential therapies for underlying conditions. This involves patient education on a low-potassium diet (e.g., limiting bananas, durian, tomatoes, potatoes), avoiding salt substitutes containing potassium chloride, and medication optimization. A key modern principle, emphasized in the Malaysian Consensus, is to enable RAASi therapy in patients with CKD and heart failure. Rather than stopping these life-saving drugs at the first sign of hyperkalemia, the strategy is to proactively manage the potassium. This is achieved with diet, optimizing diuretics, and, crucially, the chronic use of novel oral potassium binders like Patiromer or SZC. This allows the patient to remain on, and even have their dose of, the essential cardiorenal protective medication optimized, fundamentally improving their long-term prognosis (9).

When to Escalate

Call Your Senior (MO/Specialist) if:

  • The patient has any ECG changes, regardless of the potassium level.

  • The serum potassium is > 6.5 mmol/L.

  • The patient develops new neurological signs (e.g., weakness) or becomes hemodynamically unstable.

  • The hyperkalemia is refractory to initial medical therapy (e.g., failure of K+ to fall by 0.5 mmol/L in 2 hours).

  • The cause of hyperkalemia is a massive, ongoing release (e.g., severe rhabdomyolysis).

Referral Criteria:

  • Refer to the Nephrology team for any patient requiring hemodialysis, for advice on managing hyperkalemia in ESRD, or for initiating long-term potassium binders.

  • Refer to the Endocrinology team if adrenal insufficiency is suspected, for formal dynamic testing and hormone replacement.

References

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  2. Palmer, B. F., & Clegg, D. J. (2017). Pathogenesis, diagnosis and management of hyperkalemia. Cleveland Clinic Journal of Medicine, 84(12), 934–942. https://doi.org/10.3949/ccjm.84a.17050

  3. Bailey, M. A., & Unwin, R. J. (2017). An integrated view of potassium homeostasis. N Engl J Med, 376, 1358-1368. https://www.nejm.org/doi/full/10.1056/NEJMra1615362

  4. Viera, A. J., & Wouk, N. (2015). Potassium disorders: Hypokalemia and hyperkalemia. American Family Physician, 92(6), 487-495. https://www.aafp.org/pubs/afp/issues/2015/0915/p487.html

  5. Simon, L. V., Hashmi, M. F., & Farrell, M. W. (2024). Hyperkalemia. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK470284/

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  7. Ministry of Health Malaysia. (2020). National Health and Morbidity Survey (NHMS) 2019: Non-communicable diseases, healthcare demand, and health literacy. Institute for Public Health.

  8. UpToDate. (2025). Causes and evaluation of hyperkalemia in adults. Retrieved July 12, 2025, from https://www.uptodate.com

  9. National Heart Association of Malaysia, Malaysian Society of Nephrology, & Malaysian Endocrine and Metabolic Society. (2024). The Malaysian Consensus on the Management of Acute & Persistent Hyperkalaemia. https://www.msn.org.my/wp-content/uploads/2024/10/Consensus-Statements-for-Managing-HK-FINAL.pdf

  10. DynaMed. (2025). Hyperkalemia in Adults - Approach to the Patient. Retrieved July 12, 2025, from https://www.dynamed.com

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  12. North Bristol NHS Trust. (n.d.). Hyperkalaemia in Primary Care. Retrieved July 12, 2025, from https://www.nbt.nhs.uk/sites/default/files/Hyperkalaemia%20in%20Primary%20Care.pdf

  13. Montague, B. T., Ouellette, J. R., & Buller, G. K. (2008). Retrospective review of the frequency of ECG changes in hyperkalemia. Clinical Journal of the American Society of Nephrology, 3(2), 324–330. https://doi.org/10.2215/CJN.04611007

  14. Palmer, B. F. (2015). A physiologic-based approach to the development of a treatment for hyperkalemia. American Journal of Kidney Diseases, 66(2), 349-357.

  15. Hollander-Rodriguez, J. C., & Calvert, J. F., Jr. (2006). Hyperkalemia. American Family Physician, 73(2), 283–290. https://www.aafp.org/pubs/afp/issues/2006/0115/p283.html

  16. LITFL. (2022). Hyperkalaemia ECG changes. Life in the Fast Lane. https://litfl.com/hyperkalaemia-ecg-library/

  17. Ab Rahman, N. A., Mohd, R., & Che'ng, A. Z. (2021). Hyperkalemia in Patients with Type 2 Diabetes Mellitus: Risk Factors and its Association with In-Hospital Mortality. Endocrinology and Metabolism International Journal, 9(4), 133-138. https://ej-clinicmed.org/index.php/clinicmed/article/view/291

  18. UPMC. (n.d.). Hyperkalemia Causes, Symptoms, and Treatments. Retrieved July 12, 2025, from https://www.upmc.com/services/kidney-disease/conditions/hyperkalemia

  19. The Royal Children's Hospital Melbourne. (2021). Clinical Practice Guidelines: Hyperkalaemia. Retrieved July 12, 2025, from https://www.rch.org.au/clinicalguide/guideline_index/hyperkalaemia/

  20. Gennari, F. J. (1998). Hyperkalemia: An adaptive response in chronic renal failure. Kidney International, 54(5), 1345-1355.

  21. UK Kidney Association. (2022). Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults. https://www.ukkidney.org/sites/default/files/RENAL%20ASSOCIATION%20HYPERKALAEMIA%20GUIDELINE%20-%20JULY%202022%20V2_0.pdf

  22. Al-Absi, H. R., & Al-Absi, A. R. (2023). Consensus document on the management of hyperkalemia. Nefrología (English Edition), 43(4), 385-402. https://doi.org/10.1016/j.nefroe.2023.09.001

Danial Mirza
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