Hyperkalaemia

The mantra: Stabilise, shift, remove. Calcium follows the ECG; insulin-glucose follows a confirmed K+ at or above 6.5 even when the trace is still quiet.^[33][2]

Meet the patient

A 68-year-old man with CKD stage 4, on ramipril and spironolactone for heart failure with reduced ejection fraction, is called up from the GP for a routine bloods repeat. His potassium is 7.1 mmol/L. He feels "a bit weak climbing the stairs" and the nurse notices tall, peaked T waves on the monitor. The combination is classic — an ACE inhibitor and a mineralocorticoid antagonist are two of the commonest drug causes of hyperkalaemia, particularly when renal reserve is reduced.^[20][31]

Two exam questions are now live, and you must answer both before you leave the bedside: is this number real? and what do you do in the next five minutes? Everything below exists to answer those two questions at consultant depth.^[1]

What hyperkalaemia is — and the one principle that runs the page

Hyperkalaemia is a serum potassium at or above 5.5 mmol/L (Lehnhardt: exceeds 5.5 mmol/L; UKKA uses the ERC threshold of at least 5.5 mmol/L), and it is one of the few potentially lethal electrolyte disturbances. Some reviews use a 5.0 mmol/L laboratory cutoff — do not mix that number with the UKKA/ERC bands on this page. A rise in extracellular potassium alters the resting membrane potential of cardiac myocytes and can degenerate into ventricular fibrillation or asystole while the bloods are still spinning.^[10][33][1]

The job at the bedside is always the same three moves, in this order: confirm the number is true by excluding pseudohyperkalaemia, grade severity by combining the concentration with the ECG, and deliver the three-step ladder — stabilise, shift, remove — while the cause is corrected in parallel.^[1][2]

The principle that decides every management call on this page: calcium follows the ECG; a potassium at or above 6.5 still needs the shift-and-remove ladder. UKKA gives intravenous calcium when there is ECG evidence of hyperkalaemia, and treats severe hyperkalaemia (K+ at or above 6.5 mmol/L) urgently with insulin-glucose even if the trace is quiet. Geldermann's emergency review also gives calcium for ECG changes or K+ at or above 6.5 mmol/L. A wildly raised potassium with a normal ECG and no symptoms is pseudohyperkalaemia until the sample is repeated — but a confirmed 6.5 or above is not left untreated because the printer looks pretty.^[33][2][22]

The severity bands — 5.5 and 6.5 are the numbers that matter

Hyperkalaemia is defined as a potassium at or above 5.5 mmol/L. UKKA classifies mild 5.5 to 5.9 mmol/L, moderate 6.0 to 6.4 mmol/L, and severe at or above 6.5 mmol/L. The two thresholds that change management are 5.5 (the disease is real — stop the drug, repeat the sample) and 6.5 or any ECG change (the emergency threshold — the ladder runs in parallel). Calcium is for ECG change (UKKA 6.8 mmol equivalent); insulin-glucose is for confirmed severe hyperkalaemia even if the ECG is still quiet.^[10][33][2]

^{[33] [2] [23]}

The pseudohyperkalaemia trap — repeat the sample first

Before you treat an asymptomatic patient with a normal ECG, prove the number is real. Pseudohyperkalaemia is a laboratory artefact: the reported serum K+ is raised while the in vivo plasma K+ is normal. It is induced by haemolysis and excessive leakage of potassium from cells during or after blood collection, and it is increasingly recognised in haematological disorders with leucocytosis and thrombocytosis. Treating it is treating nothing — and it is the single most common reason a junior reaches for calcium in a patient who never needed it.^[22]

The causes cluster into three:^[22]

• In vitro haemolysis — prolonged tourniquet time, fist-clenching, traumatic tap, under-filled or delayed samples. The plasma looks pink.
• Extreme thrombocytosis — platelets release K+ as the clot forms in the serum tube.
• Extreme leucocytosis — classically in chronic lymphocytic leukaemia; fragile white cells lyse during processing. Comparing a serum with a plasma (heparin) potassium exposes the gap — and in leukaemia the reverse pattern (plasma higher than serum, from heparin-induced cell-membrane damage) is also described.^[22]

Everyone forgets: the fix is mechanical, not pharmacological. Repeat the sample without a tourniquet, no fist-clenching, prompt analysis — or send an arterial blood gas K+. A normal ECG in an asymptomatic patient with a wildly raised K+ is pseudohyperkalaemia until proven otherwise.^[22]

Who gets it — the cause review

True hyperkalaemia is uncommon in the community and dominant in the patients the exam focuses on: anyone with reduced renal reserve, anyone on a renin-angiotensin-aldosterone system (RAAS) blocker, and anyone with sudden cell breakdown. Sort the causes into three buckets — impaired excretion, transcellular shift, increased load.^[31][9]

Bucket 1 — impaired renal excretion (the commonest):^[31][9]

• CKD and end-stage kidney disease — reduced renal reserve is the substrate on which everything else lands; in dialysis patients a missed session is the prototypical precipitant.
• AKI — especially oliguric phases, or when rhabdomyolysis and tumour lysis add a potassium load.
• Hypoaldosteronism — primary (Addison disease) or hyporeninaemic; in patients with diabetic nephropathy, hyperkalaemia may be caused by the syndrome of hyporeninaemic hypoaldosteronism.^[9]
• Drug-induced — ACE inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, NSAIDs, calcineurin inhibitors (ciclosporin, tacrolimus), heparin, aldosterone antagonists, potassium-sparing diuretics, trimethoprim and pentamidine. Inhibition of the renin-angiotensin-aldosterone system is the single most important drug mechanism, and acute episodes are commonly triggered by the introduction of a medication affecting potassium homeostasis.^[20][9]

Bucket 2 — transcellular shift out of cells:^[31]

• Metabolic acidosis and insulin deficiency (DKA can present with a high serum K+; replacement is a recognised controversy once insulin starts).
• Tissue breakdown — tumour lysis, rhabdomyolysis, haemolysis, severe burns, crush injury.
• Beta-blockade and other transmembrane offenders — beta-blockers, calcium channel blockers, suxamethonium and mannitol all alter transmembrane potassium movement.^[20]
• Succinylcholine (suxamethonium) — see the scenarios section; the upregulated-receptor trap.^[25]

Bucket 3 — increased load:^[31]

• Dietary indiscretion — potassium-rich foods (banana, avocado, dried fruit, tomato, potato, beans, coconut water) and potassium-chloride salt substitutes; dietary counselling is part of long-term management.^[31]
• Massive transfusion and potassium-containing drugs — a genuine increased-intake load on top of reduced excretion.^[31]
• Tumour lysis — K+ with phosphate and urate from haematological malignancy induction (Burkitt, ALL).^[31]

The RAAS-drug story examiners love: In RALES, spironolactone 25 mg daily added to standard therapy in severe HFrEF cut the risk of death by 30 percent — and serious hyperkalaemia in the trial was minimal. The real-world echo is the exam point: after RALES was published, spironolactone prescribing in Ontario rose abruptly and hyperkalaemia hospitalisation rose from 2.4 to 11.0 per 1000 patients on ACE inhibitors, with associated mortality rising from 0.3 to 2.0 per 1000 — 560 excess hyperkalaemia hospitalisations in a single year. The lesson is not "fear the drug"; it is "monitor, and use binders to keep the life-saving drugs running".^[18][19]

Why it kills — membrane depolarisation in one paragraph

Potassium is the predominant intracellular cation; clinical deterioration ensues when extracellular concentration rises, because the ratio of intracellular to extracellular K+ — set by the Na+/K+-ATPase — is the resting membrane potential. A rise in extracellular K+ depolarises the membrane, inactivates fast sodium channels, slows conduction (wide QRS), shortens the action potential (peaked T), and at the far end dissolves organised atrial and ventricular activity into sine wave, then asystole.^[3]

Total-body potassium turns on three taps: intake, transcellular distribution, and excretion.^[21]

• Intake — a typical daily dietary K+ intake is about 100 mmol, most of it absorbed in the small intestine.^[21]
• Distribution — insulin, beta-2 stimulation and alkalosis push K+ into cells; insulin deficiency, beta-blockade, acidosis and hypoaldosteronism pull it out.^[31][20]
• Excretion — the kidney excretes the bulk of the dietary load via the distal tubules; about 10 percent of ingested K+ leaves via the intestine, and in chronic renal insufficiency colonic K+ secretion is greatly enhanced and becomes an important accessory excretory pathway — the physiological reason gut binders work.^[21]

Acidosis shifts K+ out, and the DKA paradox. Insulin deficiency drives transcellular potassium shifts in DKA, so the serum can read high on arrival. DKA management means reversing metabolic derangements while correcting volume depletion, electrolyte imbalances and acidosis together, with potassium replacement one of its recognised controversies. Protocolised monitoring matters because potassium can fall once insulin starts — Barski does not quantify a whole-body deficit, so do not quote one from this paper.^[29]

Impaired renal excretion is the dominant mechanism in most clinical hyperkalaemia, with transcellular shift and increased intake as the amplifiers — which is why "stop the drug, treat the kidney, then bind the load" closes most cases.^[31][1]

What you see at the bedside — and what you won't

Hyperkalaemia is usually silent. Symptoms are non-specific and predominantly related to muscular or cardiac dysfunction; the first sign may be the ECG, the lab report, or cardiac arrest. Emergent treatment is recommended for patients with clinical signs and symptoms (muscle weakness, paralysis) or ECG abnormalities.^[10][31]

Symptoms, when present:^[10][31]

• Muscle weakness — ascending, proximal; difficulty rising from a chair or climbing stairs; rarely progresses to flaccid quadriparesis.
• Fatigue and paraesthesia, and nausea with abdominal pain from visceral smooth-muscle dysfunction.
• Palpitations, light-headedness, presyncope or syncope from bradyarrhythmia or transient asystole.
• Sudden cardiac death — ventricular fibrillation or asystole may be the first manifestation.

Signs to look for:^[31][28]

• Vital signs — bradycardia in advanced hyperkalaemia; hypotension if volume-depleted or in Addisonian crisis.
• Neuromuscular — proximal then distal weakness; reduced or absent reflexes at very high K+.
• Skin — buccal and palmar crease pigmentation points to primary adrenal insufficiency.
• Volume status — oedema, oliguria, dehydration, or surgical losses (drains, stomas, fistulae).

The ECG ladder — peaked T to sine wave

This is the section where a normal trace can coexist with a lethal number and an obviously terminal trace can sit at a moderate concentration. Treat the ECG, not the number — the ECG identifies cardiac conduction disturbances, but it may not correlate with serum potassium levels, so record it, trend it, and let its severity — not the printer — drive escalation.^[31]

The ordered peaked-T → PR/P-wave → QRS → sine-wave ladder is conventional teaching, not an enumerated sequence in the papers cited on this page. UKKA notes that even small elevations above 6.5 mmol/L can lead to rapid progression from peaked T waves to ventricular fibrillation or asystole.^[33]

• Peaked T waves (tall, narrow-based, symmetric), best seen in the precordial leads — the most widely appreciated sign, and, importantly, rarely by itself the manifestation of life-threatening hyperkalaemia.^[23]
• PR prolongation, flattening then loss of P waves as atrial conduction fails.
• QRS widening with deep S waves — conduction through the His-Purkinje system and ventricular muscle slows.
• Sine-wave morphology dissolving into ventricular fibrillation, pulseless ventricular tachycardia or asystole.

Capture a rhythm strip with every intervention. If the ECG is improving the ladder is working; if it is worsening, escalate to definitive removal — dialysis remains the definitive option in refractory cases.^[2]

Bedside assessment — ECG before history

The order at the bedside is fixed: ECG first, then a brief cause-focused history, then a focused examination. A wide QRS or sine wave mandates treatment before you take any further history.^[2][31]

1. The ECG — before the second blood sample. Continuous 12-lead and cardiac monitoring. The trace may be normal even at a high K+, and may be grossly abnormal at a moderate number — record it and trend it.^[31]

2. Vital signs and circulation. Bradycardia in advanced hyperkalaemia is ominous and precedes asystole. Hypotension with hyponatraemia and hyperpigmentation is Addisonian crisis until proven otherwise — an adrenal crisis presents systemically unwell with non-specific signs, and infection is the major precipitant.^[28]

3. Focused examination for the cause. Heart sounds and JVP for volume status; lung bases for pulmonary oedema in ESRD; buccal pigmentation for Addison disease; surgical wounds, drains and stomas for losses; proximal-then-distal weakness with reduced reflexes.^[31][9]

4. Volume status and urine output. Oliguria or a rising creatinine marks a renal cause — document urine volume and chart fluid balance; dialysis may be needed where there is end-stage renal disease, severe renal impairment, or ongoing potassium release.^[31]

Investigations — what to draw, and in which order

Bedside, immediately:^[31]

• ECG (12-lead plus rhythm strip) — before any other investigation; document the trace.
• Capillary glucose — DKA is both a mimic and a precipitant, and low pretreatment glucose is a published risk factor for insulin-induced hypoglycaemia.^[4]
• Continuous monitoring during therapy.

Blood, drawn with the initial sample:^[31][22]

• Repeat venous K+ without tourniquet (or ABG K+) to confirm true hyperkalaemia and exclude pseudohyperkalaemia — but do not wait for it if the ECG is abnormal.
• Arterial blood gas — pH and bicarbonate; bicarbonate therapy is only for the acidotic.
• Urea, creatinine, electrolytes, eGFR — renal function; hyponatraemia points to Addison or volume overload.
• CK for rhabdomyolysis; urate and phosphate for tumour lysis.
• Glucose and ketones for DKA and HHS.
• Plasma cortisol when Addison is in play — but treatment of adrenal crisis starts before the result.^[28]
• Digoxin level — digoxin inhibits the Na+/K+-ATPase, so hyperkalaemia accompanies toxicity and predicts its mortality; treat the toxicity, not just the potassium.^[26]
• Full blood count with film — leucocytosis and thrombocytosis raise pseudohyperkalaemia; eosinophilia suggests drug-induced interstitial nephritis.^[22]

Urine and imaging, driven by the suspected cause:^[31][9]

• Urinalysis, urine osmolality and sodium for pre-renal versus intrinsic AKI.
• Renal ultrasound in new AKI to exclude obstruction; bilateral small echogenic kidneys in CKD.
• Chest radiograph for pulmonary oedema; CT where tumour lysis or retroperitoneal pathology is suspected.

The three-step ladder — resuscitation

This is the emergency section. Do the steps in parallel where you can, but never skip step 1 if the ECG is abnormal.^[2][1]

^{[33] [3] [5] [6] [8] [4]}

Step 1 — Stabilise the membrane (calcium)

Calcium does NOT lower potassium. Intravenous calcium is effective in reversing electrocardiographic changes and reducing the risk of arrhythmias but does not lower serum potassium — it restores the gap between resting and threshold potentials and buys you a window of conduction stability while you get on with the rest of the ladder.^[9][3]

• Calcium salts — two teaching numbers, not one. Long (US emergency review): calcium gluconate 10% 10 mL intravenously for membrane stabilisation; 10 mL calcium chloride if the patient is in cardiac arrest. UKKA: calcium chloride or gluconate at an equivalent dose of 6.8 mmol when there is ECG evidence of hyperkalaemia — 10 mL 10% calcium chloride = 6.8 mmol Ca2+; 10 mL 10% calcium gluconate = 2.26 mmol Ca2+, so three gluconate ampoules match the chloride dose. It is effective within 3 minutes; repeat if there is no effect within 5-10 minutes; duration 30-60 minutes. Do not quote 10 mL of gluconate as 10 mmol — that is the chloride salt.^[3][33]
• Geldermann's emergency review also lists calcium for ECG changes or serum potassium at or above 6.5 mmol/L. Name the disagreement rather than collapsing it.^[2]
• Honesty for the viva: IV calcium salts have never been tested in an RCT for hyperkalaemia, and in a randomised blinded pig model of hyperkalaemic arrest calcium chloride did not improve return of spontaneous circulation (19 of 26 vs 18 of 26) while bicarbonate did (24 of 26, 92 percent, vs 13 of 26, 50 percent). Give calcium for the ECG — and know the evidence base.^[7][32]

Step 2 — Shift potassium into cells (insulin, salbutamol, bicarbonate)

This step lowers the number but does not remove potassium from the body — it is a bridge, not a destination.^[7]

• Insulin 10 units of soluble (short-acting) insulin intravenously with glucose. UKKA: 10 units in 25 g glucose for severe hyperkalaemia (K+ at or above 6.5 mmol/L, 1B) and suggested for moderate 6.0 to 6.4 mmol/L. Harel's systematic review: a 10-unit bolus lowered K+ by 0.78 mmol/L at 60 minutes, versus 0.79 mmol/L with 20 units infused over 60 minutes (no significant difference); a 10-unit infusion fell only 0.39 mmol/L — do not call bolus and infusion equivalent. Harel recommends 50 g glucose with 10 units and 60 g with 20 units because almost one fifth of pooled patients became hypoglycaemic. UKKA adds 10% glucose at 50 mL/h for 5 hours (25 g) if pretreatment glucose is under 7.0 mmol/L, and monitors glucose for up to 12 hours. Moussavi: hourly glucose for at least 4 to 6 hours. An alternative Harel regimen for K+ over 6.5 mmol/L or marked ECG changes is 20 units over 60 minutes with 60 g of glucose.^[33][5][4]
• Salbutamol 10 to 20 mg nebulised — adjuvant, not monotherapy. In Allon's double-blind placebo-controlled haemodialysis study the fall was evident by 30 minutes and sustained for at least 2 hours, with maximal falls of 0.62 mmol/L after the 10-mg dose and 0.98 mmol/L after the 20-mg dose and no significant blood-pressure or heart-rate changes. In the Cochrane review the peak effect of 10 mg was at 120 minutes (mean difference -1.29 mmol/L vs placebo) and of 20 mg at 90 minutes (-1.18 mmol/L), IV and nebulised routes were comparable, and salbutamol performed similarly to insulin-dextrose and better than bicarbonate at 60 minutes. Combine it with insulin. UKKA: 10 to 20 mg as adjuvant for severe (1B); do not use salbutamol as monotherapy in severe hyperkalaemia (1A).^{[6][7][2][33]}
• Sodium bicarbonate — a small, select role. In the classic crossover study of non-diabetic haemodialysis patients, isotonic bicarbonate alone did not significantly lower plasma potassium (-0.03 mmol/L) and did not potentiate insulin or albuterol; current reviews confine its indication to patients with severe comorbid conditions and metabolic acidosis. Not for routine use.^[8][2]

Step 3 — Remove total-body potassium (diuretic, binder, dialysis)

This is the only step that durably lowers total-body potassium. Steps 1 and 2 buy a window; step 3 closes the account.^[7]

• Loop (and thiazide) diuretics can be useful to promote elimination where urine output is preserved — diuretics may support potassium elimination especially in volume overload, though prospective evidence in emergency populations is lacking.^[3][2]
• Sodium polystyrene sulfonate (SPS) — effectively retired. It is not efficacious, is no longer recommended due to questionable efficacy and the risk of gastrointestinal adverse events, and is associated with serious gastrointestinal adverse effects. Know it because exams and older protocols mention it — then name the newer binders.^[3][2][31]
• Sodium zirconium cyclosilicate (SZC) — 10 g three times daily for the first 48 hours, then 5, 10 or 15 g once daily for maintenance. In HARMONIZE, potassium fell from a mean of 5.6 to 4.5 mEq/L at 48 hours, median time to normalisation was 2.2 hours, 84 percent were normokalaemic by 24 hours and 98 percent by 48 hours, all three maintenance doses kept potassium lower than placebo through 28 days, and oedema was dose-related (most frequent with 15 g). Long-term data confirm correction (10 g three times daily for 24 to 72 hours) then maintenance (5 g daily for up to 12 months) works across CKD stages.^[11][12]
• Patiromer — in AMETHYST-DN (type 2 diabetes with CKD on RAAS inhibitors), starting doses of 4.2, 8.4 or 12.6 g twice daily (mild hyperkalaemia) or 8.4, 12.6 or 16.8 g twice daily (moderate) produced week-4 potassium reductions of 0.35 to 0.55 mEq/L in mild and 0.87 to 0.97 mEq/L in moderate hyperkalaemia, sustained and well tolerated through 52 weeks; the long-term analysis used 8.4 to 33.6 g per day divided twice daily, with hypomagnesaemia 7.2 percent the commonest treatment-related adverse event in the main AMETHYST-DN trial, and 8.6 percent in the Pitt heart-failure subgroup analysis.^[13][14]
• Dialysis — the definitive option. Dialysis is the most efficient means of removing excess potassium and remains the definitive option in refractory cases or end-stage renal disease; consider it with ESRD, severe renal impairment, or ongoing potassium release. Because shifting therapies only relocate potassium, pharmacological therapy is the bridge until dialysis is performed — recheck after treatment and pair every shift with a removal plan.^{[3][2][31][7]}

The resuscitation checklist, time-ordered: ECG and IV access plus ABG sample; IV calcium if the ECG is abnormal (UKKA 6.8 mmol equivalent); insulin 10 units IV with glucose (UKKA 25 g; Harel 50 g with 10 units) and hourly glucose checks out to 4-6 hours (Moussavi) and up to 12 hours (UKKA); salbutamol 10 to 20 mg nebulised as adjuvant; bicarbonate not routinely; a loop diuretic if urine output and volume allow; SZC or patiromer for binder removal; dialysis if refractory, ESRD or ongoing release.^{[33][3][5][6]}

Definitive management — stop the cause, bind the load

Once the immediate threat is controlled, treat the cause and lower total-body K+ in parallel. Five moves, none optional.^[31][2]

1. Stop the K+-retaining drugs. ACE inhibitors, ARBs, direct renin inhibitors, NSAIDs, calcineurin inhibitors, heparin, aldosterone antagonists, potassium-sparing diuretics, trimethoprim and pentamidine are the established offenders — increased awareness, monitoring and prevention are the key elements of reducing drug-induced hyperkalaemia.^[20]

2. Correct volume status and treat the cause.^[31]

• Addison disease / adrenal crisis — emergency treatment is prompt recognition plus parenteral hydrocortisone, rehydration and management of electrolyte abnormalities. Do not wait for the cortisol result; infection is the major precipitant, and an adrenal crisis may be the first presentation.^[28]
• DKA or HHS — management requires reversing the metabolic derangements while correcting volume depletion, electrolyte imbalances and acidosis; potassium replacement is one of the recognised controversies, so follow a protocol and monitor potassium as insulin starts.^[29]
• Tumour lysis syndrome — aggressive hydration and early dialysis where potassium release is ongoing; dialysis is explicitly indicated in the setting of ongoing potassium release.^[31]
• Rhabdomyolysis and AKI — treat the cause, balance fluid, prepare dialysis if oliguric or release is ongoing.^[31]
• Hyporeninaemic hypoaldosteronism — the classic cause of hyperkalaemia in diabetic nephropathy; address the drug load and the kidney, not just the number.^[9]

3. Diet — the paradigm has shifted. Dietary potassium restriction has long been considered a core strategy for chronic hyperkalaemia in CKD, but this is now challenged by evidence favouring more liberalised, plant-based patterns, with novel potassium binders and gut potassium handling offering a way to incorporate heart-healthy potassium-containing foods. Individualise with a renal dietitian rather than issuing a blanket ban.^[30][15]

4. Chronic binder therapy. Patiromer and SZC lower potassium, maintain normokalaemia long-term (AMETHYST-DN, HARMONIZE and their extensions), and — the exam-winning point — may facilitate optimisation of RAAS inhibitor therapy, while SPS carries serious gastrointestinal risk.^{[13][11][16][31]}

5. Keep the life-saving RAAS drugs running. In acute heart failure hospitalisations, incident hyperkalaemia was common but patients discharged on the same or increased dose of MRAs or ACE inhibitors/ARBs had better 180-day survival — so do not permanently stop these drugs for a number you can bind. Re-challenge with binder cover and individualised monitoring; increased monitoring frequency is advised for patients with CKD, diabetes, heart failure, prior hyperkalaemia, or those on RAAS inhibitors.^[17][16]

The scenarios that trap you

These are the stems examiners reach for first. Know each one cold.^[2]

Addisonian crisis. Hyperkalaemia with hyponatraemia, hypotension, hyperpigmentation and shock is primary adrenal insufficiency until proven otherwise. Emergency treatment is parenteral hydrocortisone with rehydration and electrolyte correction — do not wait for the cortisol result to treat.^[28]

Tumour lysis syndrome. Rapidly rising K+ with phosphate, hypocalcaemia and urate in a chemotherapy-treated haematological malignancy (Burkitt, ALL). Established TLS gets aggressive hydration, the full hyperkalaemia ladder, and early dialysis where potassium release is ongoing.^[31]

Succinylcholine (suxamethonium). A depolarising neuromuscular blocker that can provoke a lethal hyperkalaemic response. In pathological states — upper or lower motor denervation, prolonged immobilisation, infection, direct muscle trauma, muscle tumour or inflammation, and burn injury — acetylcholine receptors up-regulate and spread throughout the muscle membrane, so succinylcholine depolarises the whole surface and drives potassium efflux from muscle into the extracellular space. Avoid it in these groups; if given inadvertently, treat as hyperkalaemic emergency/arrest.^[25]

Digoxin toxicity. Hyperkalaemia from Na+/K+-ATPase inhibition is itself a severity marker — each 1 mEq/L rise in potassium carried a mortality odds ratio of 1.5 in a 161-patient series. Definitive treatment is digoxin-specific antibody fragments: in a published case, 40 mg of antibody fragments rapidly normalised potassium and heart rate after calcium gluconate, insulin-glucose and bicarbonate had all failed — even with a therapeutic serum digoxin concentration. And the "stone heart" fear is retired: intravenous calcium caused no life-threatening dysrhythmias and did not increase mortality in digoxin-toxic patients, so do not withhold calcium from a dying patient — but recognise it will not fix the toxicity.^[26][27]

DKA recovery. Management corrects volume, electrolytes and acidosis together, and potassium replacement is a recognised controversy that demands protocolised monitoring rather than improvisation — potassium can fall once insulin starts.^[29]

Massive transfusion. Large-volume transfusion is an increased-load cause on top of reduced excretion — treat acute hyperkalaemia with the standard ladder (calcium first if the ECG is abnormal) and recheck frequently while the transfusion continues.^[31]

Beta-blocker and other drug effects. Non-selective beta-blockers (with calcium channel blockers, suxamethonium and mannitol) are the drugs that alter transmembrane potassium movement; RAAS-inhibiting drugs dominate the impaired-excretion list. In any hyperkalaemia, the drug chart is part of the differential.^[20]

Special populations

• Paediatric — hyperkalaemia is the same potentially lethal condition with the same logic (reduced excretion, excessive intake, leakage from the intracellular space, non-specific muscular and cardiac dysfunction, immediate treatment to shift potassium into cells and increase elimination); the pathogenesis-and-management review to quote is paediatric, and dosing is weight-adjusted on local protocol.^[10]
• Older adults — high-risk polypharmacy (RAAS inhibitors, NSAIDs, potassium-sparing diuretics), reduced GFR, and frequently missed Addison disease; drug awareness, monitoring and prevention are the named countermeasures.^[20][9]
• Dialysis-dependent ESRD — the missed-session patient is the prototypical emergency; haemodialysis is the definitive removal option, and prevention means binder therapy, diet education and a plan for the inter-dialytic interval.^[2]
• Heart failure on RAAS inhibition plus CKD — high-risk, high-benefit: RALES cut mortality with spironolactone 25 mg daily, and maintaining or up-titrating MRA/ACEi/ARB despite incident hyperkalaemia was associated with better 180-day survival. Use patiromer or SZC to enable continuation rather than stopping the life-saving drugs.^[18][17][16]
• Transplant recipients — calcineurin inhibitors (ciclosporin, tacrolimus) cause hyperkalaemia via impaired renal excretion; coordinate drug levels with the transplant team.^[20]

Complications and prognosis

Complications^[31][2]

• Arrhythmia and cardiac arrest — bradycardia, AV block, wide-complex tachycardia, ventricular fibrillation, asystole; pre-terminal sine-wave morphology. In hyperkalaemic arrest, guidelines pair IV calcium chloride and sodium bicarbonate with standard ALS — though in a randomised pig model bicarbonate improved ROSC (92 vs 50 percent) while calcium chloride did not.^[32]
• Neuromuscular — ascending weakness, rarely flaccid quadriparesis; usually reversible.^[10]
• Recurrence — hyperkalaemia recurs, particularly in CKD with RAAS inhibition (the post-RALES data), which is the argument for long-term binder therapy and monitoring rather than a one-off fix.^[19][16]
• Treatment-related — insulin-induced hypoglycaemia (almost one fifth of pooled patients; monitor hourly for 4-6 hours), SPS gastrointestinal injury (why it is no longer recommended), and the general truth that no acute pharmacological therapy has been shown in RCTs to reduce mortality or arrhythmia — safety and monitoring matter as much as efficacy.^[4][2][7]

Prognosis. Hyperkalaemia is one of the few potentially lethal electrolyte disturbances, and prompt recognition with expeditious treatment is expected to save lives — but quantify it honestly: no clinical study has demonstrated a reduction in adverse patient outcomes with any of the acute drugs, so the prognostic lever is early recognition, ECG-guided treatment and definitive removal. Risk-stratified disposition: mild and reversible goes home with a recheck and a drug review; moderate or with an ongoing cause is admitted with a binder; severe, ECG-changed or oliguric goes to a monitored bed with continuous ECG and repeat potassium until out of the arrhythmogenic window.^[1][7][2]

Long term, the goal is not a normal number for its own sake — it is keeping RAAS inhibition running: binders may facilitate optimisation of RAAS inhibitor therapy, and patients maintained on MRA/ACEi/ARB despite hyperkalaemia had better 180-day survival. Individualised monitoring (more frequent with CKD, diabetes, heart failure, prior hyperkalaemia or RAAS inhibitors) closes the loop.^[16][17]

Evidence and guidelines — what to quote

Consensus and guideline-level:^[15][2]

• KDIGO Controversies Conference (Clase 2020, Kidney Int) — potassium homeostasis in kidney disease: dietary paradigm shift away from blanket restriction, and therapeutic approaches for both chronic and emergency hyperkalaemia.^[15]
• UKKA / Renal Association 2020 (Alfonzo et al.) — ERC threshold at or above 5.5 mmol/L; mild 5.5-5.9, moderate 6.0-6.4, severe at or above 6.5; calcium 6.8 mmol equivalent for ECG change (effective within 3 minutes); insulin-glucose 10 units in 25 g; salbutamol 10-20 mg adjuvant not monotherapy; bicarbonate not routine; calcium resonium not for emergency severe hyperkalaemia; glucose monitoring up to 12 hours.^[33]
• Geldermann 2026 (Emerg Med J) — emergency-care review: calcium for ECG changes or K+ at or above 6.5; insulin-glucose with hypoglycaemia vigilance; salbutamol combined with insulin; bicarbonate only for acidosis with severe comorbidity; SPS retired; SZC and patiromer promising; haemodialysis definitive.^[2]
• Cochrane review (Batterink 2015) — the honest-evidence anchor: salbutamol (any route) and IV insulin-dextrose are the most effective potassium-lowerers; no study showed improved patient-important outcomes; IV calcium and resins never RCT-tested.^[7]

Landmark trials and key papers:^{[11][13][18][19]}

• HARMONIZE (Kosiborod 2014, JAMA) — SZC 10 g three times daily for 48 hours then 5-15 g daily: median time to normalisation 2.2 hours, 98 percent normokalaemic by 48 hours, potassium lower than placebo through 28 days, oedema dose-related.^[11]
• AMETHYST-DN (Bakris 2015, JAMA; Pitt 2018, ESC Heart Fail) — patiromer twice-daily dosing reduced potassium 0.35-0.55 mEq/L (mild) and 0.87-0.97 mEq/L (moderate) at week 4, effective and well tolerated to 52 weeks.^[13][14]
• RALES (Pitt 1999, NEJM) — spironolactone 25 mg daily cut all-cause mortality by 30 percent in severe HFrEF; serious hyperkalaemia minimal in-trial.^[18]
• Juurlink 2004 (NEJM) — the post-RALES echo: hyperkalaemia hospitalisation rose from 2.4 to 11.0 per 1000 and associated mortality from 0.3 to 2.0 per 1000 in older patients on ACE inhibitors.^[19]
• Harel & Kamel 2016 (PLoS One) — 10-unit bolus lowered K+ 0.78 mmol/L at 60 minutes vs 0.79 mmol/L with 20 units over 60 minutes; 10-unit infusion only 0.39 mmol/L; almost one fifth hypoglycaemia; 50 g glucose with 10 units, 60 g with 20 units.^[5]
• Allon 1989 (Ann Intern Med) / Allon & Shanklin 1996 (AJKD) — nebulised albuterol 10 and 20 mg dose-response; bicarbonate alone ineffective and non-potentiating.^[6][8]

Practice points that travel well:^[30]

• Cost and availability shape binder choice globally: insulin-dextrose, calcium and salbutamol are universal and cheap; SZC and patiromer are the costly newcomers; SPS is cheap but retired on safety grounds.^[2]
• Diet is no longer a blanket ban — restriction is being reconsidered in the binder era in favour of liberalised plant-based patterns.^[30]
• Monitoring is the cheapest intervention: individualise frequency, and increase it for CKD, diabetes, heart failure, prior hyperkalaemia and RAAS inhibitor therapy.^[16]

Ward-round test

Four stems the registrar will fire on a hyperkalaemia round. Work them before you reveal.^[2]

Stem 1 — The asymptomatic 7.1 (answer)ShowHide

A 68-year-old on ramipril and spironolactone, K+ 7.1 mmol/L, normal ECG, feels well. What is the first move — and what is the trap? The trap is pseudohyperkalaemia. Pseudohyperkalaemia is induced by haemolysis and excessive potassium leakage during or after collection, and clusters with marked leucocytosis and thrombocytosis. Repeat the sample without a tourniquet, no fist-clenching, or send an ABG K+, and compare serum with plasma potassium if the counts are high. Only if the repeat is confirmed do you run the ladder — but an abnormal ECG is treated on the spot, sample or no sample.^[22]

Stem 2 — Peaked T waves and K+ 7.4 (answer)ShowHide

The monitor shows peaked T waves and the blood gas reads K+ 7.4 mmol/L. First drug, dose, and why. IV calcium now — it does NOT lower serum potassium; it reverses ECG changes. Quote both numbers: Long 10 mL 10% gluconate (arrest: 10 mL chloride); UKKA 6.8 mmol equivalent (10 mL 10% chloride, or three 10 mL gluconate ampoules). Then insulin 10 units IV with glucose (UKKA 25 g; Harel 50 g with 10 units) plus salbutamol 10 to 20 mg nebulised as adjuvant, and arrange removal. Do not wait for a repeat sample when the ECG is diagnostic.^{[3][33][9][5]}

Stem 3 — The weak and shaky hour (answer)ShowHide

Sixty minutes after insulin 10 units IV with dextrose, the patient is sweaty, tremulous and confused. What happened and what was missed? Hypoglycaemia — almost one fifth of patients in the pooled experience, with low pretreatment glucose, no diabetes, female gender, abnormal renal function and lower body weight the published risk factors. Glucose must be checked hourly for at least 4 to 6 hours (Moussavi) and up to 12 hours (UKKA) because insulin can outlast the dextrose bolus. Treat with IV dextrose and fix the chart.^[4][5][33]

Stem 4 — Hyperkalaemia, hyponatraemia, hypotension (answer)ShowHide

K+ 7.0 mmol/L, Na+ 124 mmol/L, BP 84/50, buccal pigmentation. Diagnosis and the first moves. Addisonian crisis. Emergency treatment is prompt parenteral hydrocortisone with rehydration and electrolyte management — do not wait for the cortisol result. The mineralocorticoid deficiency is driving the potassium; run the standard hyperkalaemia ladder in parallel, and remember infection is the major precipitant to hunt.^[28]

References33ShowHide

1. [1]Weisberg LS. Management of severe hyperkalemia Crit Care Med, 2008.PMID 18936701
2. [2]Geldermann N, Dzimiera J, Fischer H, et al. Acute hyperkalaemia in emergency care: evidence-based approaches Emerg Med J, 2026.PMID 41506858
3. [3]Long B, Warix JR, Koyfman A. Controversies in Management of Hyperkalemia J Emerg Med, 2018.PMID 29731287
4. [4]Moussavi K, Fitter S, Gabrielson SW. Management of Hyperkalemia With Insulin and Glucose: Pearls for the Emergency Clinician J Emerg Med, 2019.PMID 31084947
5. [5]Harel Z, Kamel KS. Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review PLoS One, 2016.PMID 27148740
6. [6]Allon M, Dunlay R, Copkney C. Nebulized albuterol for acute hyperkalemia in patients on hemodialysis Ann Intern Med, 1989.PMID 2919849
7. [7]Batterink J, Cessford TA, Taylor RA. Pharmacological interventions for the acute management of hyperkalaemia in adults Cochrane Database Syst Rev, 2015.PMID 35658162
8. [8]Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol Am J Kidney Dis, 1996.PMID 8840939
9. [9]Hollander-Rodriguez JC, Calvert JF. Hyperkalemia Am Fam Physician, 2006.PMID 16445274
10. [10]Lehnhardt A, Kemper MJ. Pathogenesis, diagnosis and management of hyperkalemia Pediatr Nephrol, 2011.PMID 21181208
11. [11]Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial JAMA, 2014.PMID 25402495
12. [12]Roger SD, Lavin PT, Lerma EV, et al. Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study Nephrol Dial Transplant, 2021.PMID 32030422
13. [13]Bakris GL, Pitt B, Weir MR, et al. Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial JAMA, 2015.PMID 26172895
14. [14]Pitt B, Bakris GL, Weir MR, et al. Long-term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin-converting enzymes/angiotensin receptor blockers: results from AMETHYST-DN ESC Heart Fail, 2018.PMID 29767459
15. [15]Clase CM, Carrero JJ, Ellison DH, et al. Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference Kidney Int, 2020.PMID 31706619
16. [16]Palmer BF, Carrero JJ, Clegg DJ. Clinical Management of Hyperkalemia Mayo Clin Proc, 2021.PMID 33160639
17. [17]Beusekamp JC, Tromp J, Cleland JGF, et al. Hyperkalemia and Treatment With RAAS Inhibitors During Acute Heart Failure Hospitalizations and Their Association With Mortality JACC Heart Fail, 2019.PMID 31606364
18. [18]Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure N Engl J Med, 1999.PMID 10471456
19. [19]Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study N Engl J Med, 2004.PMID 15295047
20. [20]Ben Salem C, Badreddine A, Fathallah N, et al. Drug-induced hyperkalemia Drug Saf, 2014.PMID 25047526
21. [21]Sorensen MV, Matos JE, Praetorius HA, Leipziger J. Colonic potassium handling Pflugers Arch, 2010.PMID 20143237
22. [22]Meng QH, Wagar EA. Pseudohyperkalemia: A new twist on an old phenomenon Crit Rev Clin Lab Sci, 2015.PMID 25319088
23. [23]Littmann L, Gibbs MA. Electrocardiographic manifestations of severe hyperkalemia J Electrocardiol, 2018.PMID 30177318
24. [24]Diercks DB, Shumaik GM, Harrigan RA, et al. Electrocardiographic manifestations: electrolyte abnormalities J Emerg Med, 2004.PMID 15261358
25. [25]Martyn JAJ, Richtsfeld M. Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms Anesthesiology, 2006.PMID 16394702
26. [26]Levine M, Nikkanen H, Pallin DJ. The effects of intravenous calcium in patients with digoxin toxicity J Emerg Med, 2011.PMID 19201134
27. [27]Graafsma J, Cimic N, Dijkman M, et al. Digoxin toxicity with therapeutic serum digoxin concentrations Toxicol Rep, 2025.PMID 40687894
28. [28]Dineen R, Thompson CJ, Sherlock M. Adrenal crisis: prevention and management in adult patients Ther Adv Endocrinol Metab, 2019.PMID 31223468
29. [29]Barski L, Golbets E, Jotkowitz A, Schwarzfuchs D. Management of diabetic ketoacidosis Eur J Intern Med, 2023.PMID 37419787
30. [30]Sumida K, Biruete A, Kistler BM, et al. New Insights Into Dietary Approaches to Potassium Management in Chronic Kidney Disease J Ren Nutr, 2023.PMID 37610407
31. [31]Kim MJ, Valerio C, Knobloch GK. Potassium Disorders: Hypokalemia and Hyperkalemia Am Fam Physician, 2023.PMID 36689973
32. [32]Eggertsen MA, Munch Johannsen C, Kovacevic A, et al. Sodium Bicarbonate and Calcium Chloride for the Treatment of Hyperkalemia-Induced Cardiac Arrest: A Randomized, Blinded, Placebo-Controlled Animal Study Crit Care Med, 2024.PMID 37921685
33. [33]Alfonzo A, Harrison A, Baines R, Chu A, Mann S, MacRury M. Clinical Practice Guidelines: Treatment of Acute Hyperkalaemia in Adults UK Kidney Association (Renal Association), 2020.Source