New fatigue and weakness in a patient with heart failure, CKD and polypharmacy
A 74-year-old man (78 kg) with heart failure with reduced ejection fraction (LVEF 32%), type 2 diabetes and stage 3b chronic kidney disease comes to your community pharmacy reporting two weeks of fatigue, poor appetite and new generalized muscle weakness. He has no palpitations, syncope or chest pain; his pulse is regular at 62 beats/min and blood pressure is 104/66 mmHg. Current medications: sacubitril/valsartan 97/103 mg twice daily (started 3 weeks ago), carvedilol 6.25 mg twice daily, spironolactone 25 mg daily, dapagliflozin 10 mg daily, furosemide 40 mg each morning, potassium chloride 20 mEq daily (started 4 weeks ago when serum potassium was 3.8 mmol/L), and ibuprofen 400 mg three times daily, which he began 10 days ago for knee pain. Blood work drawn yesterday: potassium 5.6 mmol/L, sodium 133 mmol/L, creatinine 210 micromol/L (baseline 168), eGFR 26 mL/min/1.73 m2 (baseline 38). He asks whether he should simply stop taking the water pill.
1. Identify and rank the medication-related problems most likely responsible for this patient's hyperkalemia and acute kidney injury, justifying each.
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The scenario is a predictable pharmacodynamic and hemodynamic stack, not a single culprit.
- Ibuprofen, started 10 days ago - the timing matches the creatinine rise almost exactly. NSAIDs remove prostaglandin-mediated afferent arteriolar dilation, so renal perfusion falls when an ARNI, an SGLT2 inhibitor and a loop diuretic are already reducing effective circulating volume. Prostaglandin inhibition also suppresses renin and aldosterone release, directly reducing potassium excretion, and blunts the natriuretic effect of furosemide. This is the highest-yield, most reversible contributor.
- Potassium chloride 20 mEq daily - started when potassium was 3.8 mmol/L, i.e. supplementation began without a documented ongoing indication and was then layered on a RAAS blocker plus a mineralocorticoid receptor antagonist.
- Spironolactone plus sacubitril/valsartan - additive hyperkalemia through aldosterone blockade and reduced angiotensin II drive; the ARNI was up-titrated only 3 weeks ago, so the patient has not yet been re-checked at steady state.
- Dapagliflozin and furosemide - volume depletion (sodium 133, BP 104/66) driving pre-renal azotemia rather than hyperkalemia directly.
Carvedilol is not a plausible contributor. Weakness with potassium 5.6 mmol/L is a genuine arrhythmia risk, not a laboratory nuisance to be filed away.
2. What are your immediate actions - what would you hold, whom would you contact, and what triage decision is appropriate? Justify each choice.
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Triage first. Potassium 5.6 mmol/L plus new weakness warrants same-day medical assessment (emergency department, or urgent prescriber contact with a committed plan); if potassium reaches 6.0 mmol/L, if there are ECG changes, or if he cannot be reassessed the same day, send him to the emergency department directly. Do not reassure and book him for next week.
Answer his question honestly: stopping furosemide would be the wrong move - it would remove potassium excretion and worsen the hyperkalemia.
Hold or stop: potassium chloride (no current indication), ibuprofen (stop, and do not substitute another oral NSAID), spironolactone (until potassium and creatinine are known to have recovered). Consider holding sacubitril/valsartan if potassium is still rising or if he cannot be reassessed within 24–48 hours, but recognize it is the more important long-term drug: the goal is to strip out reversible contributors and re-titrate, not to abandon disease-modifying therapy. Dapagliflozin can usually continue unless he is acutely unwell or volume-depleted.
Communicate specifically: contact the prescriber with the exact list of holds, the laboratory values and the request for repeat electrolytes and creatinine in 3–7 days after the interventions.
Counsel: avoid potassium-containing salt substitutes ('NoSalt', 'Half Salt') and read labels; these are a common and easily missed re-loading source.
3. What analgesic plan and non-drug advice would you recommend for his knee pain, and what additional counselling does the case require?
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The analgesic choice must avoid systemic prostaglandin inhibition while remaining effective enough that he does not simply return to ibuprofen.
Recommended: topical diclofenac gel to the knee (systemic exposure is roughly a small fraction of oral dosing, so renal and hyperkalemic risk are far lower) plus acetaminophen up to 3 g/day, bearing in mind his age and any hepatic risk factors. If topical therapy fails, discuss intra-articular corticosteroid with the prescriber rather than escalating to an oral NSAID. Avoid tramadol as a reflexive opioid substitution: it is not benign in CKD and carries hypoglycemia, hyponatremia and fall risk.
Non-drug: activity as tolerated, quadriceps strengthening and physiotherapy referral, weight management, a cane or walking aid for offloading, heat.
Additional counselling specific to this case:
- Explain that any over-the-counter product can matter, and that 'natural' or 'herbal' does not mean safe - he should ask before buying cough, cold, effervescent or antacid products, several of which carry potassium or sodium loads.
- Warn that his dry cough or a future ACE inhibitor switch requires a 36-hour washout before starting sacubitril/valsartan, and that he must tell any new prescriber he takes it.
- Confirm he knows to hold nothing on his own except as agreed, and give a written summary of what was held and when the repeat blood work is due.