Three kilograms of fluid, a sore knee and a naproxen prescription
Mr Alan Whitfield is 74, weighs 88 kg and has heart failure with reduced ejection fraction (LVEF 28 per cent), atrial fibrillation and chronic kidney disease. His medicines are perindopril 5 mg daily, carvedilol 6.25 mg twice daily, spironolactone 25 mg daily, frusemide 40 mg daily, atorvastatin 40 mg daily and apixaban 5 mg twice daily. Ten days ago his GP prescribed naproxen 500 mg twice daily for knee osteoarthritis. He comes into the pharmacy short of breath, having gained 3 kg, and cannot lie flat. Blood pressure is 105/65, pulse 92, potassium is 5.6 mmol/L and creatinine is 175 micromol/L (previously 130). He asks whether he can just buy something stronger for his knee.
1. Explain, step by step, how the naproxen produced this presentation.
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1. Renal haemodynamics Naproxen inhibits COX-1 and COX-2, reducing renal prostaglandin synthesis. Prostaglandins keep the afferent arteriole dilated. In a patient with heart failure and reduced effective circulating volume, that prostaglandin drive is the main thing holding glomerular perfusion pressure up. Remove it, and add an ACE inhibitor (which dilates the efferent arteriole) and a loop diuretic (which reduces intravascular volume), and GFR falls sharply - creatinine 130 to 175.
2. Sodium and water retention Prostaglandin inhibition increases tubular sodium reabsorption and blunts both the diuretic and the antihypertensive effect of his other medicines. The result is the 3 kg gain, orthopnoea and decompensated heart failure.
3. Hyperkalaemia Naproxen-induced hyporeninaemic hypoaldosteronism, on top of an ACE inhibitor, spironolactone and a falling GFR, gives the potassium of 5.6 mmol/L.
4. Bleeding COX-1 inhibition impairs platelet thromboxane production, adding to the bleeding risk of apixaban and to the gastrointestinal mucosal injury of an NSAID.
5. Timing Naproxen has a long half-life (roughly 12-17 hours) and twice-daily dosing means sustained prostaglandin suppression - the temporal link with the 10-day prescription makes it the clear precipitant.
2. Which of his current medicines need action today, and how do you assess whether his apixaban dose is now too high?
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Naproxen: cease immediately. This is the precipitant and continuing it makes every other problem worse.
Spironolactone: withhold. Potassium 5.6 with acute kidney injury, an ACE inhibitor and an NSAID is a potentially life-threatening combination. Recheck potassium and creatinine within 24-48 hours and consider an ECG if potassium climbs above 6.0 or there are changes on the tracing.
Perindopril: discuss withholding during the acute illness/AKI; at minimum recheck electrolytes. Sick-day rules apply here.
Frusemide: he is congested, not dry, so diuresis will likely be increased - but that is a medical decision. My job is to get him seen today: 3 kg gain with orthopnoea and a potassium of 5.6 needs same-day medical review, not a counter adjustment.
Apixaban - do not reduce reflexively. The reduced dose of 2.5 mg twice daily requires two of: age 80 or over; weight 60 kg or less; serum creatinine 133 micromol/L or more. He meets only one criterion (creatinine 175) - he is 74 and 88 kg. He therefore stays on 5 mg twice daily. Check a full blood count and watch for bleeding, and reassess renal function once he recovers, because the creatinine criterion will resolve.
Carvedilol and atorvastatin: continue; carvedilol may need review if he becomes hypotensive or bradycardic.
3. He wants something stronger than paracetamol for the knee. Construct an analgesic plan and the counselling that goes with it.
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Avoid
- All oral NSAIDs, including COX-2 selective agents. In NYHA III-IV heart failure they cause fluid retention and decompensation, worsen renal function, antagonise diuretics and ACE inhibitors, and add to apixaban bleeding risk. This is a contraindication, not a relative caution.
- Opioids and compound codeine products: little evidence in osteoarthritis, and in an older adult they cause falls, constipation and delirium.
Use
- Paracetamol 1 g up to four times daily, with a review of total daily intake. In a frail 74-year-old I would cap at 3 g/day and check he is not already taking combination products containing paracetamol.
- Topical diclofenac 1 per cent gel, 2-4 g to the knee up to four times daily. Systemic exposure is a small fraction of oral dosing, which makes it a reasonable option, but not a zero-risk one: apply only to the knee, no occlusive dressing, and monitor weight and oedema.
- Non-drug measures: physiotherapy with quadriceps strengthening, weight management, a walking stick, heat, and pacing of activity.
- If symptoms remain uncontrolled, an intra-articular corticosteroid via the GP is worth discussing, with attention to anticoagulation and technique.
Counselling
- Explain plainly why the naproxen has put him in this position and that his heart and kidneys are the reason.
- Tell him not to buy ibuprofen, naproxen or combination cold and flu products, and to check with the pharmacy every time before buying anything for pain.
- Give red flags: weight gain of 2 kg or more in three days, waking short of breath, needing more pillows, dizziness or fainting.
- Document the conversation and send a note to the GP.