Tramadol- and codeine-induced severe hyponatremia: A Swedish population-based case-control study

Area of Science:

• Pharmacology
• Clinical Medicine
• Epidemiology

Background:

• Limited evidence exists on the association between weak opioids like tramadol and codeine and hyponatremia.
• Previous reports suggest these drugs may cause hyponatremia, but data is scarce.

Purpose of the Study:

• To investigate the association between the use of weak opioids (tramadol and codeine) and hospitalization due to hyponatremia.
• To differentiate the risks associated with newly initiated versus ongoing opioid therapy.

Main Methods:

• A register-based case-control study utilizing the general Swedish population.
• 14,359 cases hospitalized with hyponatremia were compared to 57,383 matched controls.
• Multivariable logistic regression adjusted for co-medications, diseases, prior hospitalizations, and socioeconomic factors.

Main Results:

• Newly initiated tramadol or codeine use showed a significantly increased adjusted odds ratio (OR) for hyponatremia hospitalization (2.34 and 2.20, respectively).
• Ongoing therapy with tramadol or codeine did not reveal an elevated risk (adjusted ORs 0.70 and 1.14, respectively).
• Unadjusted ORs were higher, but adjusted ORs for overall use were modest (1.17 for tramadol, 1.14 for codeine).

Conclusions:

• A notable association exists between tramadol or codeine initiation and hospitalization for hyponatremia.
• The risk of hyponatremia hospitalization is not increased with long-term use of these weak opioids.
• While a causal drug effect is possible, confounding factors like pain or underlying conditions cannot be ruled out.