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 7 was a 57-year-old male who was found at the base of a stairway. The patient neurologically deteriorated in the field, with decline in the GCS from 13 to 8, was intubated in the emergency department, and was admitted to the neuroscience intensive care unit. CT scans showed hemorrhagic contusions, subdural hematoma, and traumatic SAH. ICP, ptiO2, and rCBF probes, and intraparenchymal depth electrodes were placed in the right frontal lobe and continuous scalp DC/AC-EEG was monitored using Ag/AgCl-electrodes. Five SDs were observed on day 2, and elevated ICP at >40mmHg became intractable despite administration of muscle relaxants, pentobarbital, and 3% saline. Per discussions with family, a DNR-CC order was placed on day 5 and the patient was terminally extubated. Approximately 10 minutes thereafter, a slow, homogeneous DC shift was observed on intraparenchymal DC/AC-ECoG and scalp DC/AC-EEG electrodes in synchrony with the decline in oxygen saturation and PtiO2, a final ICP spike, and declining cerebral perfusion and respiratory arrest. Nonspreading depression was observed across intraparenchymal and scalp electrodes during the falling phase of ptiO2. Asystole for 20 seconds began 3 minutes later, only 13 seconds before the start of terminal SD (Fig ).