An observational study in Intracranial Hypertension and Cerebral Edema, sponsored by Neuromed IRCCS. Withdrawn at 1 site in Italy. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2020-11-19.
Sponsored by Neuromed IRCCS · Observational
Osmotherapy consists in the therapeutic use of osmotically active substances with the aim of reducing the volume and therefore the intracranial pressure. It therefore represents an essential component in the clinical management of cerebral edema and intracranial hypertension, whether they are a consequence of head trauma, ischemic or hemorrhagic stroke, and neoplasm or neurosurgical procedures.
The current study aims at evaluating in vivo the effects on haemostasis parameters of hypertonic saline solutions at different concentration, as compared to mannitol, in patients with neuroradiological signs (CT / MRI) of cerebral edema / non-traumatic intracranial hypertension.
Osmotherapy is commonly used in the treatment of intracranial hypertension (ICH) due to a variety of causes, including head trauma, intracranial neoplasia, infection or hemorrhage, and status epilepticus. The principle goal of osmotherapy is to shift fluid from the intracellular into the extracellular compartment using intravenous hyperosmolar agents, thereby reducing brain edema and improving cerebral perfusion pressure. Although 10-20% mannitol is considered the gold standard hyperosmolar agent in the treatment of ICH, mannitol-induced osmotic diuresis may cause hypovolemia and reduction in cerebral perfusion pressure. In recent years, 3.0-7.5% hypertonic saline (HTS) has gained popularity in the treatment of ICH as it has less pronounced diuretic effects and therefore does not cause hypovolemia. Indeed, in the face of hypovolemic shock and traumatic brain injury, HTS provides the advantage of volume expansion, restoring adequate cerebral perfusion pressures, and reducing brain edema, which makes it superior to mannitol in trauma patients with shock.
Both mannitol and HTS have been shown to interfere with whole blood coagulation and platelet function. This is in part due to dilutional coagulopathy. Furthermore, 7.2% HTS may directly disturb both fibrin formation and platelet function, and mannitol may interfere with coagulation by reducing clot strength. In addition, hyperosmolarity is supposed to lead to impairment of both whole blood coagulation and platelet function . In consequence, the safety of using these agents in patients with ICH and intracranial hemorrhage remains unclear. Previous in vitro studies in humans have demonstrated anticoagulant effects of both mannitol and HTS, although one clinical study failed to demonstrate any negative effect on hemostasis using either solution in patients undergoing elective intracranial surgery. However, in vivo studies in a clinical setting are lacking.
Patients (men and women) with cerebral edema / intracranial hypertension (CT / MRI neuroradiological diagnosis) on a non-traumatic basis with indication to osmotic therapy, treated on the basis of clinical and radiological evidence according to current treatment standards and meeting the inclusion criteria.
Exclusion Criteria:
Mannitol 0.2-0.3 g/kg 4 times/day.
Drug: Mannitol
Hypertonic saline solution 3%. Continous infusion of 0,5 ml/kg/h. If necessary a loading dose of 2,5 ml/kg is administered.
Drug: Hypertonic saline solution
Hypertonic solution saline 4%. Continous infusion of 0,5 ml/kg/h. If necessary a loading dose of 2,5 ml/kg is administered.
Drug: Hypertonic saline solution
Hypertonic saline solution 7%. Continous infusion of 0,5 ml/kg/h. If necessary a loading dose of 2,5 ml/kg is administered.
Drug: Hypertonic saline solution
Therapy is administered according to the clinical gold standard and until reaching and maintaining serum sodium levels between 145 e 155 meq/l and an osmolarity \<320.
Therapy is administered according to the clinical gold standard and until reaching and maintaining serum sodium levels between 145 e 155 meq/l and an osmolarity \<320.
Changes in coagulation parameters
Coagulation parameters such as thrombin and prothrombin time, fibrinogen, thrombin generation time will be measured in plasma by ELISA test or on whole blood by thromboelastography
Time frame: Before osmotic therapy (time 0), after 12 hrs infusion (time 1)
Changes in inflammation markers
Inflammation markers such as C reactive protein, interleukin 6, P-selectin. E-selectin will be measured in plasma
Time frame: Before osmotic therapy (time 0), after 12 hrs infusion (time 1)
Plan to share: No
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Neuromed IRCCS