The cardiac membrane stabilisation principle of calcium gluconate is one of the most important emergency pharmacology facts in primary care — IV calcium gluconate does NOT lower the serum potassium. Its mechanism is to raise the threshold potential of the cardiac myocyte membrane, reducing the depolarisation risk from the elevated extracellular K⁺. It buys time (approximately 30–60 minutes) while definitive K⁺-lowering measures are initiated. This distinction matters because: (1) calcium gluconate must be given first if there are ECG changes, while simultaneously preparing insulin-dextrose; and (2) the patient still has hyperkalaemia after calcium — follow-up K⁺-lowering is mandatory. The onset of action is 1–3 minutes; duration is 30–60 minutes. If ECG changes do not improve after one dose, a second dose can be given. Pseudohyperkalaemia is responsible for a substantial proportion of 'hyperkalaemia' results in primary care — estimated at 20–40% of K⁺ results above 5.5 mmol/L. The mechanism is potassium released from red blood cells during haemolysis in the sample tube, which can be caused by: prolonged tourniquet use (avoid or release after vein entry), repeated fist clenching (dramatically increases local K⁺), delayed sample processing (red cell K⁺ leaks into plasma over time), mechanical trauma during venepuncture, and extreme thrombocytosis or leucocytosis (release from platelets/WBCs — check FBC). The clinical implication is that a single asymptomatic K⁺ result of 5.5–6.4 mmol/L in a patient without CKD, without precipitating drugs, and with a haemolysed or borderline sample should always be repeated before any clinical action, including stopping medications. However, if ECG changes or symptoms are present at any K⁺ level — act immediately.

The ACEi/ARB + spironolactone triple therapy combination for heart failure is the highest-risk prescribing scenario for hyperkalaemia in primary care — RALES trial (spironolactone + ACEi in CHF) showed 30% reduction in mortality but a 2% rate of serious hyperkalaemia. When ARBs are added to ACEi + spironolactone (quadruple RAAS blockade, sometimes seen in complex heart failure management), the hyperkalaemia risk is very high. Guidelines recommend monitoring K⁺ and eGFR 1–2 weeks after each dose change and at least every 4–6 months in stable patients. The trimethoprim hyperkalaemia mechanism is underappreciated — trimethoprim at the high doses used for Pneumocystis jirovecii pneumonia prophylaxis (960 mg OD) structurally resembles amiloride and blocks the epithelial sodium channel (ENaC) in the distal nephron with the same mechanism as K⁺-sparing diuretics, causing meaningful K⁺ retention. This is clinically significant in patients on trimethoprim prophylaxis who also have CKD, are taking ACEi/ARB, or have other K⁺-elevating risk factors. K⁺-containing salt substitutes (LoSalt and similar products contain approximately 350 mg of K⁺ per gram — compared to approximately 0 mg in regular NaCl) are frequently recommended by dietitians and cardiologists for hypertension management without specific warning to patients with CKD or on ACEi/ARB. These products can cause dangerous hyperkalaemia in at-risk patients. Asking about salt substitute use should be part of the dietary history in any patient with hyperkalaemia.

The ECG changes of hyperkalaemia follow a predictable progression from mild to severe, and the QRS width is the single most important parameter for urgency — a widened QRS (>120 ms) from hyperkalaemia indicates that the ventricular conduction system is critically compromised, and VF or cardiac arrest can occur within minutes. This makes QRS width more important than the absolute K⁺ level: a K⁺ of 6.0 with a QRS of 140 ms is more immediately dangerous than a K⁺ of 7.0 with a narrow normal QRS. The peaked T waves are the earliest ECG sign and can appear at K⁺ levels of 5.5–6.0 — they are tall, narrow, and symmetrical, best seen in the precordial leads (V2–V4), and are often described as 'tented' (pointed rather than rounded apex). This contrasts with the tall broad asymmetric T waves of myocardial ischaemia. The sine wave pattern (QRS and T wave fusing into a continuous oscillating waveform) represents an immediately pre-arrest rhythm — any patient with a sine wave ECG should receive IV calcium gluconate immediately and 999 should be called if in primary care. The risk stratification table is important for primary care decision-making — the dividing lines between 'phone 999,' 'send to hospital same day,' and 'urgent next-day review' are based on K⁺ level, ECG status, symptoms, and renal function. A K⁺ of 6.2 with a haemolysed sample, normal ECG, and no symptoms in a patient with CKD-3b warrants a repeat blood test rather than a 999 call — but the clinician must be certain the ECG is genuinely normal before making this decision.

The ACEi + ARB + spironolactone combination (sometimes called 'triple RAAS blockade') is explicitly discouraged in most UK guidelines because of the high risk of hyperkalaemia and AKI without additional cardiovascular benefit compared to optimal single-agent RAAS blockade. NICE guidance on CKD (NG203) specifically states that dual RAAS blockade (ACEi + ARB together) should not be used. The prescribing scenario that commonly creates triple RAAS blockade is: a GP prescribes ACEi for hypertension/heart failure, a cardiologist adds spironolactone for resistant hypertension or heart failure, and the patient also self-medicates with ibuprofen — neither prescriber sees the complete picture. Medication reconciliation at each consultation (reviewing the full drug list including OTC medications) is the single most important preventive action for iatrogenic hyperkalaemia. The salt substitute issue deserves special attention because it creates a false sense of safety: patients with CKD or heart failure who have been advised to reduce salt intake appropriately switch to salt substitutes — which contain potassium chloride instead of sodium chloride and can deliver several grams of potassium per day. A patient with CKD-4 on spironolactone who uses LoSalt liberally and eats a high-potassium diet can have K⁺ levels that are genuinely dangerous. This dietary history question takes 30 seconds to ask but is rarely included in hyperkalaemia assessments.

Patiromer (Veltassa) and sodium zirconium cyclosilicate (Lokelma) are two novel K⁺-binding agents approved by NICE (TA623 for patiromer in CKD, TA599 for SZC) that represent a significant advance in chronic hyperkalaemia management in primary care. Unlike the traditional calcium/sodium polystyrene sulphonate (Resonium — primarily a hospital acute treatment), patiromer and SZC are well-tolerated oral preparations specifically designed for long-term outpatient use. They work by binding K⁺ in the gastrointestinal tract and preventing its absorption, providing a sustained K⁺-lowering effect over days to weeks. Clinical significance: these drugs allow patients who were previously unable to tolerate optimal RAAS blockade for heart failure or CKD (because their K⁺ rose unacceptably) to remain on life-saving medications. NICE has approved patiromer for adults with CKD who require RAAS inhibitor therapy and have hyperkalaemia, and SZC for hyperkalaemia in adults with CKD or heart failure. GPs should be aware of these options for patients with chronic recurrent hyperkalaemia on RAAS therapy — initiation may be in secondary care initially but continuation and monitoring falls to primary care. Dose: patiromer 8.4 g OD (titrate to 16.8 g OD if needed); SZC 5 g TDS × 48 hours (loading), then 5 g OD maintenance.

The insulin-dextrose infusion is the cornerstone of acute hospital hyperkalaemia management and works via a beautifully simple physiological mechanism — insulin activates the Na⁺/K⁺-ATPase pump on skeletal muscle cells, driving K⁺ from the extracellular space into the intracellular compartment. This is why hyperkalaemia is a key feature of diabetic ketoacidosis (absent insulin) despite total body K⁺ depletion (K⁺ cannot enter cells without insulin). The dextrose is given simultaneously to prevent the hypoglycaemia that the exogenous insulin would otherwise cause. The glucose monitoring protocol after insulin-dextrose is mandatory because hypoglycaemia can occur 1–4 hours after the infusion, when insulin continues to act but the glucose bolus has been metabolised. The salbutamol additive effect is clinically important — the combination of insulin-dextrose + salbutamol is superior to either alone for acute K⁺ reduction, and both treatments can be administered simultaneously in the emergency department. The total K⁺ reduction from combined insulin + salbutamol is approximately 1.0–2.0 mmol/L — which is often sufficient to convert an immediately dangerous ECG pattern to a manageable one while dialysis is arranged if needed. GPs should understand these hospital treatments not to administer them in primary care but to explain them to patients and families, and to understand why certain drugs (especially insulin and dextrose infusions) are being given in hospital for hyperkalaemia rather than for glucose management.

Patiromer (Veltassa) is a particularly useful drug for the very common clinical scenario of heart failure + CKD + spironolactone-induced hyperkalaemia — the RAAS inhibitor combination is the cornerstone of HFrEF management with proven mortality benefit (RALES showed 30% reduction in all-cause mortality with spironolactone + ACEi), but is frequently stopped or under-dosed in primary care because of hyperkalaemia. Patiromer allows the clinician to maintain optimal RAAS blockade while controlling the K⁺ rise. The AMBER trial (2019, Lancet, n=295) showed that in patients with CKD + heart failure who would otherwise require RAAS inhibitor discontinuation due to hyperkalaemia, patiromer allowed continuation of RAAS therapy in 66% vs 43% in the placebo group at 12 weeks. This is a meaningful clinical benefit — GPs managing complex heart failure patients with CKD should be aware of patiromer as an enabling strategy. Fludrocortisone for type 4 RTA is rarely initiated in primary care but GPs may continue prescriptions started by nephrology/endocrinology. The mechanism is physiologically elegant: fludrocortisone replaces the deficient aldosterone in type 4 RTA, restoring normal distal nephron K⁺ secretion. It is the only K⁺-lowering drug that works by restoring the underlying defect (rather than binding K⁺ in the gut or shifting it intracellularly). The blood pressure monitoring requirement reflects fludrocortisone's sodium-retaining effects — it raises BP and causes mild fluid retention, which may be beneficial in Addison's disease but needs monitoring in hypertensive patients with diabetic nephropathy.

The sick day rules concept is one of the most important and underused patient safety interventions in CKD management — studies have shown that acute kidney injury (AKI) is responsible for approximately 10–15% of hospital admissions, and a significant proportion are caused by dehydration + continued nephrotoxic/RAAS drug use during illness in patients who were not told to temporarily stop these drugs. The 'STOP' mnemonic for sick day rules (Stop: Spironolactone, Trimethoprim, ACEi/ARBs, and NSAIDs during illness causing dehydration) is used in many NHS kidney patient education programmes. Written sick day rules cards (available from NHS Kidney Care/Kidney Research UK) should be given to every patient with CKD-3b or above on any combination of these drugs. The key message: 'These drugs are generally safe and important, but they can harm your kidneys and raise your potassium to a dangerous level if you become dehydrated from vomiting, diarrhoea, or not drinking enough during illness. Stop them temporarily if you can't keep fluids down for more than 24 hours, and restart them when you're better and eating and drinking normally.' The NSAID over-the-counter problem is a genuine patient safety crisis — ibuprofen is available at supermarkets and petrol stations without any prescription, and patients with CKD, heart failure, or on RAAS therapy frequently self-medicate with it for pain without realising it can cause AKI and hyperkalaemia. Verbal and written advice at each consultation, and recording the allergy/intolerance to NSAIDs in the patient's record (even if it is a relative contraindication rather than an absolute allergy) helps flag this when the patient or other prescribers attempt to prescribe it.

The 1–2 week K⁺ recheck after any ACEi/ARB dose change is a NICE-mandated monitoring requirement (CKD guideline NG203 and hypertension guideline NG136) that is frequently missed in general practice — the most common pattern of iatrogenic severe hyperkalaemia is: GP increases ACEi/ARB dose (appropriately, for blood pressure or CKD proteinuria), K⁺ rises to dangerous levels over 1–2 weeks, no repeat bloods are taken, patient develops ECG changes or cardiac arrest before the next routine blood test. The monitoring requirement is not bureaucratic box-ticking — it reflects the genuine physiological reality that RAAS agent dose increases can raise K⁺ by 0.5–1.0 mmol/L within 1–2 weeks of dose change, and this rise is unpredictable (patients with CKD-3b can have dramatic K⁺ rises to dangerous levels from a relatively small dose change). Implementing a simple practice recall system for 'K⁺ + eGFR at 1–2 weeks post-RAAS dose change' is a high-yield, low-effort patient safety intervention.