Patient 1 was a 52-year-old woman with aSAH. Until day 3, she had 13 SDs (2 spreading depressions and 11 isoelectric SDs) with a PTDDD of 487.9 minutes that occurred on day 3. On the same day, a computed tomography (CT) scan showed multiple infarcts in the territories of the right middle cerebral artery (MCA) and both posterior cerebral arteries. On the following day, a control scan revealed increasing lesions, 10mm midline shift, and beginning brain herniation. From the beginning, she required intravenous noradrenaline at a rate of 0.08 µg/kg/min to maintain adequate cerebral perfusion pressure (CPP) under sedation with propofol. Stress cardiomyopathy was ruled out using echocardiography, electrocardiography, and cardiac biomarkers. However, noradrenaline had to be further increased to 0.26 µg/kg/min on day 4 when she developed Staphylococcus aureus–caused pneumonia and midazolam was added to the sedative regimen to control progressive increase in ICP. Thiopental was added for the same reason 12 hours before she died on day 6. Thiopental resulted in cerebral isoelectricity, and intravenous noradrenaline had to be increased to a rate of 0.43 µg/kg/min. Eventually, a DNR-CC order was activated after family discussion and the patient was terminally extubated. Withdrawal of the life-sustaining treatment resulted in complete circulatory arrest after 17 minutes. Figure A shows the time course of the systemic arterial pressure including the circulatory arrest and subsequent terminal SD that started at electrode 4 and then spread to the other electrodes. For comparison, Figure C displays a typical terminal SD of a rodent brain after injection of air into the heart via the femoral vein (experimental setup in Fig D); circulatory arrest is followed by nonspreading depression and then terminal SD. The Supplementary Table provides the statistical data of 5 thiopental-anesthetized rats with previously healthy brains in which death resulted from sudden circulatory arrest by air injection into the femoral vein.
Patient 2 was a 56-year-old woman with aSAH. ICP increased up to 25mmHg despite EVD, artificial ventilation, and analgosedation. She became hemodynamically unstable and required intravenous noradrenaline at a rate of 0.56 µg/kg/min. ECoG and LDF displayed 5 SDs, which induced spreading depressions of activity, spreading ischemias of up to 190-second duration (Fig A), and spreading suppressions of low-frequency vascular fluctuations. Spreading ischemia concurred with disturbed autoregulation similar to a previous report. Accordingly, ptiO2 seemed to follow the fluctuations of mean arterial pressure (MAP). The PTDDD was 102.3 minutes and occurred on day 1.\nIn addition to a large intracerebral hemorrhage (ICH) in the right temporal lobe, magnetic resonance imaging (MRI) on day 1 revealed large infarcts in the territories of both anterior cerebral arteries, the right MCA, and both posterior cerebral arteries, as well as lacunar infarcts in right thalamus and pons. On day 2, a family discussion was held and a DNR-CC order was activated. The patient was terminally extubated. Figure B shows the nonspreading depression of activity during the falling phase of ptiO2. A very slow, homogeneous DC positivity started simultaneously with the drop in ptiO2. Superimposed on this DC positivity, the terminal SD then started at electrode 3.