sodium-oxybate and Brain-Edema

In the treatment of raised intracranial pressure (ICP) an agent is needed which can similarly reduce ICP and protect the brain without reducing systematic arterial pressure and cerebral perfusion pressure. Gammahydroxybutyrate (GHB) decreases cerebral metabolic requirement of oxygen (CMRO2) and glucose utilization rate. The effect of GHB on ICP, systemic arterial pressure and cerebral perfusion pressure in the experimentally induced brain oedema of the rat was examined. 400 mg/kg GHB reduced significantly ICP (11.74 +/- 1.20 mmHg; control: 16.20 +/- 8.89 mmHg; p less than 0.01) while increasing mean systemic arterial pressure (109.89 +/- 6.35 mmHg; control: 89.65 +/- 4.22 mmHg; p less than 0.05) and cerebral perfusion pressure (98.11 +/- 6.79 mmHg; control: 73.84 +/- 5.25 mmHg; p less than 0.02). In the dose-effect curve 200 mg/kg GHB show an increase in mean systemic arterial pressure from 89.60 +/- 9.35 mmHg to 98.60 +/- 3.48 mmHg (p less than 0.02) and 400 mg/kg GHB to 108.00 +/- 5.20 mmHg (p less than 0.001) mean systemic arterial pressure. The decrease in intracranial pressure is not due to a reduction in the mean systemic arterial pressure, but GHB does reduce the ICP while increasing mean systemic arterial pressure and cerebral perfusion pressure. GHB may be a useful adjunct to neurosurgical therapy in controlling elevated ICP.

Topics: Animals; Blood Pressure; Brain Edema; Cerebrovascular Circulation; Dose-Response Relationship, Drug; Energy Metabolism; Intracranial Pressure; Male; Rats; Rats, Inbred Strains; Sodium Oxybate

Severe head injury often produces complex intracranial displacements of the brain, resulting in widespread, often microscopic lesions. These are responsible for two types of edema: vasogenic edema, with outflow of molecules and fluid into the extracellular spaces by rupture of the blood-brain barrier and vasoplegia, and cytotoxic edema, with swelling of astrocytes due to membrane lesions. The connexions between these two types of edema are still obscure. Alterations in membrane phospholipids may impede function of Na-K pump enzymes, causing accumulation of water in the cell. Cerebral edema is responsible for intracranial hypertension and tentorial herniation, which in turn increase edema through venous compression, ischemia, and hypoxia. The least controversial anti-edema therapeutic measures include relative fluid and salt restriction, mannitol if called for, neuroplegia, in particular with diazepam and Gamma-OH, and assisted ventilation.

Topics: Alfaxalone Alfadolone Mixture; Barbiturates; Brain Edema; Brain Injuries; Cytidine Diphosphate Choline; Diazepam; Hormones; Humans; Osmolar Concentration; Prognosis; Respiration, Artificial; Sodium Oxybate; Water-Electrolyte Imbalance