Furosemide-Induced Ototoxicity: Loop of Henle
The offending agent causing this patient's hearing loss is furosemide, which acts at the ascending limb of the loop of Henle. 1
Clinical Presentation Analysis
The examination findings confirm sensorineural hearing loss:
- Weber's test lateralizes to the left (unaffected) ear 2
- Rinne's test shows AC>BC bilaterally, indicating the cochlear apparatus is damaged rather than conductive pathways 2
- Right-sided hearing loss in the setting of multiple ototoxic medications 3
Identifying the Culprit Medication
Among this patient's medications, furosemide is the most likely offender for several critical reasons:
Loop Diuretic Ototoxicity Mechanism
- Furosemide inhibits the Na+-K+-2Cl- cotransporter in the ascending limb of the loop of Henle 1, 4
- This same cotransport system exists in the marginal and dark cells of the stria vascularis, which are responsible for endolymph secretion 5
- Direct inhibition of this system in the inner ear alters ionic composition and fluid volume within the endolymph, causing ototoxicity 5
Risk Factors Present in This Patient
The FDA label specifically warns that furosemide ototoxicity is associated with:
- Rapid injection (though this patient likely received oral therapy) 3
- Severe renal impairment 3
- Use of higher than recommended doses 3
- Hypoproteinemia 3
- Concomitant therapy with other ototoxic drugs 3
This patient has multiple risk factors: heart failure with likely renal impairment, advanced age (68 years), and is on combination diuretic therapy (chlorthalidone, furosemide, acetazolamide) which may necessitate higher furosemide doses 2, 6.
Why Not the Other Medications?
- Chlorthalidone: Acts at the distal tubule, not associated with ototoxicity 1
- Acetazolamide: Acts at the proximal tubule, minimal ototoxicity risk 4
- Ramipril, metoprolol, insulin, atorvastatin: Not ototoxic agents 1
Critical Clinical Pitfalls
Synergistic Ototoxicity
The combination of multiple diuretics significantly increases ototoxicity risk 2, 7. This patient is on three diuretics simultaneously, which may have created a synergistic toxic effect even at standard doses 2.
Reversibility Concerns
While the FDA label mentions "reversible or irreversible hearing impairment," cases have shown that hearing loss may persist even after furosemide discontinuation 6. One case report documented significant hearing impairment 11 days after stopping furosemide 6.
Renal Dysfunction Amplifies Risk
Oral furosemide should be considered potentially ototoxic, particularly in patients with compromised renal function 6. Heart failure patients frequently have concurrent renal insufficiency, making them especially vulnerable 3, 6.
Answer to the Question
The loop of Henle (specifically the ascending limb) is where furosemide exerts its primary nephron effect 1, 4. The ACC/AHA guidelines explicitly state that "furosemide acts at the loop of Henle (thus, they are called loop diuretics)" 1.