Henrik Falhammar1, Jan Calissendorff2, Jakob Skov3, David Nathanson4, Jonatan D Lindh5, Buster Mannheimer6. 1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden. Electronic address: henrik.falhammar@ki.se. 2. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden. 3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 4. Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset AB, Karolinska Institutet, Stockholm, Sweden. 5. Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. 6. Department of Clinical Science and Education, Södersjukhuset AB, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND: Although tramadol and codeine occasionally have been reported to cause hyponatremia the evidence is scarce. The objective of this investigation was to study the association between weak opioids (tramadol and codeine) and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of the general Swedish population. Those hospitalized with a principal diagnosis of hyponatremia (n = 14,359) were compared with matched controls (n = 57,383). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations and socioeconomic factors was used to explore the association between severe hyponatremia and the use of tramadol or codeine. Furthermore, newly initiated (≤90 days) and ongoing use was investigated separately. RESULTS: Compared to controls, the unadjusted OR (95%CI) for hospitalization due to hyponatremia was 2.45 (2.26-2.66) for tramadol and 3.19 (2.92-3.47) for codeine. However, after adjustment for confounding factors the risk decreased (adjusted OR: 1.17 [1.08-1.26] and 1.14 [1.03-1.26], respectively). Newly initiated treatment with tramadol or codeine showed a significant association (adjusted OR 2.34 [95%CI 2.01-2.72] and 2.20 [95%CI 1.87-2.60], respectively). In contrast, for ongoing therapy the corresponding adjusted ORs were not elevated (adjusted OR: 0.70 [95%CI 0.61-0.80] and 1.14 [95%CI 0.99-1.30, respectively). CONCLUSIONS: Associations were found between tramadol or codeine usage and hospitalization due to hyponatremia which were markedly increased in those newly initiated. The risk associated with long-term use was not increased. The association may be causally related to the drugs, although an effect due to pain, nausea or the underlying disease cannot be excluded.
BACKGROUND: Although tramadol and codeine occasionally have been reported to cause hyponatremia the evidence is scarce. The objective of this investigation was to study the association between weak opioids (tramadol and codeine) and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of the general Swedish population. Those hospitalized with a principal diagnosis of hyponatremia (n = 14,359) were compared with matched controls (n = 57,383). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations and socioeconomic factors was used to explore the association between severe hyponatremia and the use of tramadol or codeine. Furthermore, newly initiated (≤90 days) and ongoing use was investigated separately. RESULTS: Compared to controls, the unadjusted OR (95%CI) for hospitalization due to hyponatremia was 2.45 (2.26-2.66) for tramadol and 3.19 (2.92-3.47) for codeine. However, after adjustment for confounding factors the risk decreased (adjusted OR: 1.17 [1.08-1.26] and 1.14 [1.03-1.26], respectively). Newly initiated treatment with tramadol or codeine showed a significant association (adjusted OR 2.34 [95%CI 2.01-2.72] and 2.20 [95%CI 1.87-2.60], respectively). In contrast, for ongoing therapy the corresponding adjusted ORs were not elevated (adjusted OR: 0.70 [95%CI 0.61-0.80] and 1.14 [95%CI 0.99-1.30, respectively). CONCLUSIONS: Associations were found between tramadol or codeine usage and hospitalization due to hyponatremia which were markedly increased in those newly initiated. The risk associated with long-term use was not increased. The association may be causally related to the drugs, although an effect due to pain, nausea or the underlying disease cannot be excluded.
Authors: Henrik Falhammar; Jakob Skov; Jan Calissendorff; Jonatan D Lindh; Buster Mannheimer Journal: J Psychopharmacol Date: 2020-07-20 Impact factor: 4.153
Authors: Henrik Falhammar; Jakob Skov; Jan Calissendorff; David Nathanson; Jonatan D Lindh; Buster Mannheimer Journal: J Clin Endocrinol Metab Date: 2020-10-01 Impact factor: 5.958
Authors: Buster Mannheimer; Henrik Falhammar; Jan Calissendorff; Jakob Skov; Jonatan D Lindh Journal: J Psychopharmacol Date: 2021-04-16 Impact factor: 4.153