Osmotic Agent Use in Middle Cerebral Artery Stroke
Condition: Ischemic Stroke; MCA Infarction
MeSH terms: Stroke; Ischemic Stroke; Infarction, Middle Cerebral Artery; Infarction
Study type: Observational

Summary: 
      This is a retrospective chart review of patients that were admitted with large MCA stroke to
      the Fairview system hospitals between December 2017-December 2018. Patients ischemic stroke
      volumes will be measured by taking the area of the infarction and multiplying it by the
      thickness of each CT or MRI slice, the summation of these volumes is the final volume of the
      ischemic lesion in cubic centimeters. Patients with stroke volumes greater than 70 cc will be
      included in the study. Patient midline shift will be measured in millimeters at the level of
      foramen of Monroe anytime during their initial admission and all patients with a shift
      greater than 1mm will be included. The midline shift will be documented on the first
      follow-up brain scan (CT or MRI) at least six hours after the initiation of osmotic therapy.
      Data will be collected from patient charts including: Age, sex, NIHSS on presentation and
      discharge, history of diabetes mellitus, hypertension, coronary artery disease, atrial
      fibrillation, and chronic kidney disease. The type of osmotherapy, along with change in serum
      sodium or osmolality and dose, will also be documented. In patients that did not receive
      osmotherapy, midline shift will be documented on the first 24-hour scan and every subsequent
      scan in 24-hour intervals. Death during a hospital stay will also be recorded.

      The investigators will use the SAS statistical suite to analyze this data.
    

Detailed description: 
      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.
    

Intervention name(s): No intervention is planned, this will be a purely retrospective trial.
Intervention type(s): Other
Intervention description(s): Osmotic Therapy
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Ischemic Stroke patients with large MCA territory Stroke of 70 CC or larger.
      
Keywords: Ischemic stroke; midline shift