Carolina, Georgia, and the Neuroscience ICU. I have no disclosures. Today we'll be talking about subarachnoid hemorrhages from preventing rebleed to multimodality monitoring. We'll start with the initial management of subarachnoid hemorrhages, prevention and treatment of complications, the use of multimodality monitoring, and a case study throughout the presentation. Let's start with the basics. While subarachnoid hemorrhages only account for 2 to 5 percent of all strokes, they're true neurological emergencies. They have high morbidity, with half of all survivors suffering from some permanent disability and mortality rate of about 12% of people will die prior to receiving medical management. Only 20% of all subarachnoid hemorrhages survive to resume their normal life by 3 to 6 months. We will use this case throughout the presentation. It's a 48-year-old female who presents to the ED with worst headache of life only three hours prior. When she arrives, she's very lethargic and can follow commands in all extremities, but she'll fall asleep during the exam. She opens her eyes to boys. Her pupils are 4, breast, ground, and reactive. Based on her physical exam, she is a Hunt and Hess 3. Her CT shows diffuse subarachnoid hemorrhage and hydrocephalus and is given a modified Fisher score of 3. The image to the right shows an example of a modified Fisher score 1 through 4, 3 and 4 being high grades. This patient has a thick subarachnoid hemorrhage defined as greater than 1 millimeter of subarachnoid hemorrhage blood without IVH. High Fisher scores have been proven to be predictive of delayed cerebral ischemia and high Hunt and Hess scores and World Federation of Neurosurgical Society scores is used to predict for outcomes. Over the course of the next hour, the patient becomes even more lethargic and eventually a patient and requires intubation prior to EVD placement. The patient has an EVD placed for early signs of hydrocephalus and CSF diversion. A CTA confirms the location of the EVD and a right MCA ruptured aneurysm. What should be our initial management of this patient? Should we start our patient on an anticonvulsant? Seizures occur in only 2% of all aneurysmal subarachnoid hemorrhage patients and most occur on presentation. No study has shown a statistical significance to benefit seizure prophylaxis. Current neurocritical care guidelines from 2011 recommend short course of less than seven days with low quality and weak recommendation and the American Heart Association guidelines recommends prophylactic anticonvulsants to be considered as a level B evidence. Risk factors for subarachnoid hemorrhages to have seizures are younger patients, MCA strokes, and more blood. Therefore, it would be reasonable to start this patient on a short course of anti-epileptic drugs. What about delayed cerebral ischemia prophylaxis? Nemodipine remains the only high quality strong recommendation for prevention of DCI due to its overall mortality benefit and its neuroprotective properties. IT fibrinolytic drugs such as ITTPA have shown to increase blood clearance and in turn prevent DCI. However, no large randomized control trial has been completed to show the overall benefit. At the University of Maryland, a study came out from March 2021 in which it showed a single center retrospective study with low dose IV heparin started within 12 hours of securing an aneurysm, decreased delayed neuro deficits when compared to sub-q heparin. Currently, a large multi-center double blind trial is underway to confirm these results. Should we start the patient on Amigard TXA, 7 to 26 percent of subarachnoid hemorrhages rebleed. Of these, the functional outcome decreases by twofold, the mortality increases by fourfold, and remains an independent factor for prognosis. Anti-fibrinolytics were evaluated in the older trial which was a multi-center prospective randomized control trial published in 2021 that looked at the use of TXA for less than 24 hours. It did not show statistical significance in the rate of rebleeds or improvement of overall clinical outcomes. It may have not shown statistical significance due to the rapid treatment and securement of an aneurysm, which may be looked at for other centers that are not able to treat and secure their aneurysms as rapidly. What about blood pressure parameters? Blood pressure control current guidelines are systolic blood pressure initially less than 160 or 180. However, this has low evidence and has not been proven to prevent rebleeding. The patient in this scenario goes for an aneurysmal repair and has a successful surgical clip place for a right MCA aneurysm. Aneurysmal repair within 24 hours of onset of headache is a high quality strong recommendation. How is the decision made by the neurosurgical colleagues to clip versus coil? An ISAT trial in 2002 showed better outcomes with endovascular coiling at one year follow-up. In 2014, a retrospective study using a large national database found that clipping was no more likely to result in complications or death compared to coiling. Now a much more tailored approach is recommended for best outcomes. Things for consideration are size, location, subarachnoid hemorrhage grade, and age of patient of the patient. What is delayed cerebral ischemia, DCI, and why does it matter? Delayed cerebral ischemia remains a major cause of death and disability in subarachnoid hemorrhages. It occurs at three to four days after initial bleed and peaks around six to eight days. It is a multifactorial process that is not fully understood. It is due in part by microvascular dysfunction, microthrombi formation, inflammation, and cortical spreading depolarizations. Interestingly about 70% of all subarachnoid hemorrhages will develop radiographic vasospasm, but only 30% develop clinical symptoms qualifying as DCI or cerebral infarct. In an awake patient, DCI is characterized as neurological change with GCS score 2 or greater that is persistent for greater than an hour and cannot be attributed to any other etiology. What ways we have to surveil for DCI? Transcranial dopplers are recommended, however, they're highly operator dependent. CTA, CTP are commonly used, however, due to their contrast are less ideal for frequent usage, and both of those methods only capture a moment in time. EEG is not sufficiently validated, however, may offer a way for surveillance in the future. What do we do in the case of our patient who continues to have a poor exam or a patient who needs to be sedated due to high ICPs and is difficult to measure neurological changes? Invasive multimodality monitoring can be used to assist in the early detection of DCI. Multimodality monitoring allows us to integrate and interpret multiple measurements and to give us a much more comprehensive view with a goal of earlier detection and possibly even prevention of DCI. For example, in a study done by RAS ETAL in 2019, higher cerebral perfusion pressures did not predict ischemia, which suggests that CPP alone is not sufficient to prevent DCI, and the other areas with multimodality monitoring may help us understand this process of ischemia better. The graphic displays several options currently being investigated. Electric corticography is when they place a strip of electrodes, either surgically or through burr holes, and it helps measure the neuronal depolarizations. Brain tissue oxygenation is when a probe is placed that measures the regional cerebral blood flow with a normal range of 25 to 50. An intervention should be applied for less than 20. A cerebral microdialysis probe is a microcatheter that can measure and detect metabolites such as glucose, lactate, pyruvate, amino acids, lactate to pyruvate ratio, and is the measure of cerebral oxygen supply, which may be a surrogate of impending hypoxia. Brain tissue oxygenation, lactate to pyruvate ratio, and glutamate are currently the most effective at diagnosing impending DCI. However, most of the studies done lack standardization and have high levels of bias. Feldman at ETAL in 2021 publication showed a retrospective cohort study of poor subarachnoid hemorrhages. Here, the authors compared patients' outcomes using a standard of care of TCDs in their first cohort over a course of four years compared to patients when they started using invasive neuromonitoring, measuring lactate and pyruvate ratios, and brain tissue oxygenation over the course of the next four years. They used the same algorithm for treatment and they found that earlier detection and treatment of DCI occurred in patients with the multi-modality monitoring and they had better outcomes measured by the Glasgow outcome extended scale at 12 months. Back to our patient. Due to poor clinical prognosis, a cerebral microdialysis probe is placed. The lactate to pyruvate ratio is greater than 40, which is generally considered a cutoff for intervention. The patient goes for a CT perfusion, which confirms radiographic vasospasm. What treatment should be initiated? Induced hypertension is considered first-line. However, an intervention is a moderate quality evidence with a strong recommendation from the Neurocritical Care Society. Intrafecal and intraventricular therapies are promising due to their local delivery. However, large randomized trials still need to occur. A study at McGill University is a retrospective study that found IT milrinone can be a rescue therapy with aggressive IV milrinone in the presence of vasospasm and can improve neurological deficits within 24 hours and a low modified Rankin score on follow-up. Persistent DCI can be treated with mechanical dilation of percutaneous transluminal balloon angioplasty for larger arteries. Chemical angioplasty with the vasodilators such as milrinone, namodipine, borapamil, and nacardipine can be used for vasospasm involving small arteries. At this point, there still needs to be large randomized control trials to better decide how to treat these patients in DCI. In conclusion, there's been many studies over the past couple years. Namodipine remains the only pharmaceutical agent with mortality benefit. Antifibrinolytics are likely not beneficial to stop re-bleeding, which we discovered from the ULTRA trial. And multimodality monitoring can be helpful, but randomized large clinical trials are still necessary. Here are my references, and thank you for listening to my presentation today.

subarachnoid hemorrhages

SAH management

neurological emergency

multimodality monitoring

neuroprotective drugs