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Hyponatremia is defined as a plasma sodium concentration below 135 mmol / L. This is a common occurrence (20-50%) during subarachnoid hemorrhage (SAH). Its appearance is often associated with vasospasm. It is associated with an increase in morbidity and mortality linked to induced neurological disorders. Hyponatremia is caused by two etiologies: the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH), and the cerebral salt wasting syndrome, CSWS. Theoretically, these two entities are differentiated by the patient's volemia; in practice, this parameter is difficult to measure. In addition, the correction of hyponatremia is diametrically opposed according to its mechanism: water restriction in the case of SIADH, sodium intake in the event of CSWS. Urea is offered as a second-line treatment in the event of treatment failure to correct hyponatremia. However, the efficacy of this treatment is based on small, observational, retrospective studies. Moreover, the mechanism of action of urea remains poorly understood: it could be a hyperosmolar effect or passive renal reabsorption of sodium.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EXPERIMENTAL GROUP | Experimental | the experimental group will be treated during 5 days by urea dose per administration : 1g / kg / 24 hours in 2 or 3 doses morning, noon and evening (dose adjustment of urea according to weight) |
|
| CONTROL GROUP | Placebo Comparator | the control group will be treated during 5 days by ergytonyl dose per administration : 5mL |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Urea | Drug | the experimental group will be treated during 5 days by urea dose per administration : 1g / kg / 24 hours in 2 or 3 doses morning, noon and evening (dose adjustment of urea according to weight) If hyponatremia persists beyond D8 after initiation of the study treatment (urea or placebo), that is to say after the date of the collection of the primary endpoint, it will be possible to introduce corticosteroids (fludrocortisone or others). These treatments will be collated. If during patient monitoring the serum sodium exceeds 145 mmol / L, treatment should no longer be administered. |
| Measure | Description | Time Frame |
|---|---|---|
| To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage | Change in blood serum in mmol / L measured before initiation of treatment and on the day of discontinuation of treatment | 5 days |
| Measure | Description | Time Frame |
|---|---|---|
| To compare the sodium intake required to correct the natremia. | Measurement of daily sodium intake in each group | 8 days |
| To study the mechanism of action of urea | Daily plasma co-peptin levels in each group during treatment and 48 hours after cessation of treatment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Perrine BOUCHEIX, MD | University Hospital, Grenoble | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Grenoble | Grenoble | 38043 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29051110 | Background | Hall A, O'Kane R. The Extracranial Consequences of Subarachnoid Hemorrhage. World Neurosurg. 2018 Jan;109:381-392. doi: 10.1016/j.wneu.2017.10.016. Epub 2017 Oct 16. | |
| 26361321 | Background | Mapa B, Taylor BE, Appelboom G, Bruce EM, Claassen J, Connolly ES Jr. Impact of Hyponatremia on Morbidity, Mortality, and Complications After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review. World Neurosurg. 2016 Jan;85:305-14. doi: 10.1016/j.wneu.2015.08.054. Epub 2015 Sep 7. |
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| ID | Term |
|---|---|
| D007010 | Hyponatremia |
| D013345 | Subarachnoid Hemorrhage |
| D007177 | Inappropriate ADH Syndrome |
| ID | Term |
|---|---|
| D014883 | Water-Electrolyte Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D020300 | Intracranial Hemorrhages |
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| ID | Term |
|---|---|
| D014508 | Urea |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
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Comparative study in 2 parallel arms, monocentric, randomized, double blind.
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|
| PLACEBO | Other | the control group will be treated during 5 days by ergytonyl dose per administration : 5mL |
|
| 48 hours after the end of treatment |
| To assess the impact of treatment on length of stay | Length of stay in intensive care and/or continuing care unit | 3 months |
| To assess the impact of treatment on neurological outcome at 3 months from inclusion | Measurement of modified Rankin score | 3 months |
| To assess the adverse effects of treatment | Prevalence of adverse effects of urea (headaches, digestive disorders, etc.) | 3 months |
| Persistence of correction of natraemia 48H after cessation of treatment | Variation in natraemia mmol/L measured before introduction of treatment and 48 hours after cessation of treatment | 48 hours after the end of treatment |
| To compare the speed of correction of natraemia | Average time taken for natraemia to correct to Na > 135 mmol/L after initiation of treatment. | 5 days |
| 24248182 | Background | Hannon MJ, Behan LA, O'Brien MM, Tormey W, Ball SG, Javadpour M, Sherlock M, Thompson CJ. Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting. J Clin Endocrinol Metab. 2014 Jan;99(1):291-8. doi: 10.1210/jc.2013-3032. Epub 2013 Dec 20. |
| 28321069 | Background | Nakajima H, Okada H, Hirose K, Murakami T, Shiotsu Y, Kadono M, Inoue M, Hasegawa G. Cerebral Salt-wasting Syndrome and Inappropriate Antidiuretic Hormone Syndrome after Subarachnoid Hemorrhaging. Intern Med. 2017;56(6):677-680. doi: 10.2169/internalmedicine.56.6843. Epub 2017 Mar 17. |
| 28174217 | Background | Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. J Am Soc Nephrol. 2017 May;28(5):1340-1349. doi: 10.1681/ASN.2016101139. Epub 2017 Feb 7. |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D004700 | Endocrine System Diseases |