Hyponatremia, Subarachnoid Hemorrhage, SIADH
Conditions
Keywords
urea, copeptine, hyponatremia, SAH, SIADH
Brief summary
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.
Interventions
DRUGUrea
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.
OTHERPLACEBO
the control group will be treated during 5 days by ergytonyl dose per administration : 5mL
Sponsors
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Comparative study in 2 parallel arms, monocentric, randomized, double blind.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged at least 18 years old * Non-traumatic HSA * Hyponatremia defined by a natremia less than 135 mmol / L and a high natriuresis, greater than 250 mmol / L despite well-managed saline intakes
Exclusion criteria
* Severe cardiac decompensation (LVEF \<30%) * Severe hepatic cirrhosis (PT \<30%, ascites), known severe renal failure (GFR \<30mL / min / 1.73m²) * Blood urea\> 25 mmol / L in the basal state * Osmotherapy and diuretics in the last 48 hours * Ongoing treatment with systemic corticosteroids * Persons referred to in Articles L1121-5 to L1121-8 of the CSP corresponding to all protected persons: pregnant woman, parturient, nursing mother, person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure. * Patient not affiliated to a social security scheme * Known hypersensitivity to any of the components of ergytonyl * Contraindications to ergytonyl: taking curative anticoagulants, previously known and treated diabetic patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage | 5 days | Change in blood serum in mmol / L measured before initiation of treatment and on the day of discontinuation of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare the sodium intake required to correct the natremia. | 8 days | Measurement of daily sodium intake in each group |
| To study the mechanism of action of urea | 48 hours after the end of treatment | Daily plasma co-peptin levels in each group during treatment and 48 hours after cessation of treatment. |
| To assess the impact of treatment on length of stay | 3 months | Length of stay in intensive care and/or continuing care unit |
| To assess the impact of treatment on neurological outcome at 3 months from inclusion | 3 months | Measurement of modified Rankin score |
| Persistence of correction of natraemia 48H after cessation of treatment | 48 hours after the end of treatment | Variation in natraemia mmol/L measured before introduction of treatment and 48 hours after cessation of treatment |
| To compare the speed of correction of natraemia | 5 days | Average time taken for natraemia to correct to Na \> 135 mmol/L after initiation of treatment. |
| To assess the adverse effects of treatment | 3 months | Prevalence of adverse effects of urea (headaches, digestive disorders, etc.) |
Countries
France
Outcome results
None listed