Osmotic Agent Use in Middle Cerebral Artery Stroke

MCA Stroke is a fatal disease with reported mortality of about 80% of cases without decompressive craniectomy. Osmotic agents like hypertonic saline & mannitol have been used in acute MCA stroke cases without no evidence of benefit. Its use in elevated ICP can be only justified as a bridge to the definitive therapy however the presumption that hypertonics will decrease the edema and thus improve shift. Cerebral edema that occurs in stroke is cytotoxic in nature & does not improve by osmotic agents. Animal studies have shown that use of osmotic agents in acute stroke might cause decrease in size of the normal brain tissue & presumably worsen the midline shift. The aim of this study is to quantitatively study the effect of hypertonic therapy on midline shift in MCA strokes.

Cerebrovascular disease is a major cause of death and disability worldwide. In 2005, the global incidence of death, due to stroke, was approximately 5.7 million, which is expected to increase to 7.8 million cases by 2030. Specifically, MCA territory stroke accounts for 90% of all infarcts and 70% of all first-time strokes. In addition, approximately half of all MCA stroke survivors never regain functional independence.

Malignant MCA syndrome is defined by an infarction of a large area of the MCA territory accompanied by a space-occupying mass effect that develops during the first 5-days after presentation. Malignant MCA infarction is found in up to 10% of all patients with supratentorial ischemia. Malignant Cerebral Infarction (MCI) typically denotes a large infarction in the MCA territory that presents with acute brain swelling in the first 48 h after stroke, with or without involvement of the ipsilateral anterior and posterior cerebral artery territories. Development of an MCI can be predicted with a sensitivity of 91% and specificity of 94% when ischemia affects more than two thirds of the MCA territory.

Malignant MCA syndrome is associated with 80% mortality in the first week despite optimal medical therapy. Death usually results from progressive swelling of the infarcted brain tissue, causing midline shift, increase in intracranial pressure (ICP), extension of ischemia to adjacent vascular territories, and eventual brain herniation. The strongest predictor of mortality is the NIHSS score. In addition, characteristics associated with mortality include: age, arrival mode, history of atrial fibrillation, previous stroke, previous myocardial infarction, carotid stenosis, diabetes mellitus, peripheral vascular disease, hypertension, history of dyslipidemia, current smoking and weekend or night admission.

In malignant MCA syndrome, standard medical therapy is directed at reducing edema and thus preventing a cascade of tissue shift, increase in ICP, and herniation. The cornerstone of medical management is osmotherapy including: mannitol and hypertonic saline, although clinical trials have shown them to be ineffective in MCA syndrome. In fact, translational studies suggest that osmotherapy may, in fact, increase the volume of infarct or midline shift and thus should be avoided. Treatment with mannitol has been associated with hypovolemia, hypotension and nephrotoxicity. Animal studies have also shown that the use of osmotic agents in acute stroke causes a decrease in the size of the normal brain tissue and thus presumably worsens the midline shift. An exclusion to these findings would include patients exhibiting signs and symptoms of mass effect, such as diminished level of arousal or nausea, and vomiting; as they are appropriate candidates for osmotherapy.

Alternatively, decompressive craniectomy (DC) has shown to significantly improve mortality outcomes from 78% to 29%. Patients 60-years-of-age or younger, that underwent DC within 48 hours of malignant stroke, had significantly reduced mortality, compared with the best medical treatment. The distribution of the modified Rankin scale (mRS) at 1 year was also significantly different: mRS of 4 or less was achieved by 75% of the patients in the group treated with DC, comparatively to only 24% in the nonoperative group. The European Stroke Organization (ESO) guidelines for the management of ischemic stroke (published in 2008) recommend DC within 48-hours after symptom onset in patients up to 60-years-of-age with evolving MCI. Overall, the goal of this study is to evaluate the osmotherapy on midline shift, a proxy for MCI related edema.