Background. Stroke is a major cause of severe disability. Working capacity is restored only in 10-20 % of stroke survivors. Stroke mortality in Ukraine is twice as high as in Western Europe. About 87 % of all strokes are ischemic strokes (II). Leading risk factors for stroke include hypertension, hypercholesterolemia, smoking, obesity, and diabetes.
Objective. To describe the management of acute IS (AIS) in the practice of an anesthesiologist.
Materials and methods. Analysis of literature data on this issue.
Results and discussion. The ideal therapeutic approach for AIS should include reperfusion, inhibition of inflammatory processes, cytoprotection, prevention of complications and their treatment. Extreme caution should be exercised during thrombolytic therapy, as thrombolysis increases the risk of intracerebral hemorrhage. However, a meta-analysis by Y. Shoujiang et al. (2018) found that symptomatic intracerebral hemorrhage occurs in 1.9 % of patients who had received intravenous recombinant tissue plasminogen activator. These hemorrhages did not increase mortality. Excellent treatment results were observed in 74.8 % of patients with AIS. According to the analysis of the VISTA database, the end result of thrombolytic therapy can be predicted based on the initial severity of stroke on the NIHHS scale. Interestingly, hemorrhagic transformation after thrombolysis is associated with lower serum calcium. Lower blood calcium levels are associated with an increased incidence of cerebral hemorrhage in patients with AIS due to atrial fibrillation or rheumatic heart disease. In the treatment of patients with AIS it is advisable to use Neurocytin (“Yuria-Pharm”), which contains citicoline and a balanced isotonic electrolyte solution. Neurocytin helps to avoid hypocalcemia and, consequently, brain hemorrhages. Citicoline is a multimodal agent with neuroprotective and neuroregenerative properties. Citicoline has a wide therapeutic window, as this substance is effective at different time and biochemical stages of the ischemic cascade. The maximum effect of citicoline is observed in cases when it is administered as early as possible after AIS in patients who cannot undergo reperfusion therapy. Citicoline is able to reduce the size of the ischemic focus in the brain. Intensive blood pressure (BP) control also reduces the risk of intracranial hemorrhages without increasing mortality, although previous studies have suggested that a rapid decrease in BP may exacerbate cerebral ischemia. Endovascular treatment of AIS in the most acute phase involves selective thrombolysis, or mechanical thrombextraction, or thromboaspiration. The therapeutic window for the last two procedures for vessels of the carotid pool is 6 hours. When deciding to perform thromboaspiration, it is mandatory to perform and evaluate computed tomography-perfusiography of the brain. About 80-85 % of patients with AIS do not meet the selection criteria for revascularization therapy. There is also no effective therapy for such patients in the acute period. In recent years, it has been proposed to replace the term “neuroprotection” with the term “brain cell cytoprotection”, as the former does not reflect the direction of the impact on all components of the neurovascular unit and white matter. A separate aspect of brain cytoprotection is protection against ischemic reperfusion injury. For this purpose, edaravon (Ksavron, “Yuria-Pharm”) is used, which eliminates free radicals, reduces calcium flow into the cells, prevents cell adhesion to the endothelium, enhances the release of nitric oxide and inhibits the inflammatory response, neutralizing all stages and consequences of ischemic stroke. In Japan, edaravon has been included into AIS treatment guidelines since 2009. T. Yamaguchi et al. (2017) found that co-administration of edaravon and recombinant tissue plasminogen activator within 4.5 hours after AIS led to less intracranial hemorrhages and better treatment outcomes. Early use of edaravon also reduces mortality. S. Kono et al. (2013) also state that edaravon may be a good adjunct to alteplase to enhance recanalization and reduce the likelihood of hemorrhagic transformation. With the administration of edaravon within the first 24 hours after stroke, one in three patients has no post-stroke sequelae, and 70 % of patients have a significant improvement in general neurological status. If edaravon is prescribed within the first 72 hours after AIS, the general condition improves significantly in half of the patients. Edaravon (Ksavron) increases the frequency of early recanalization during thrombolysis.
Conclusions. 1. Citicoline is a multimodal agent with neuroprotective and neuroregenerative properties. 2. Edaravon (Ksavron) is an ischemic cascade blocker for the empirical treatment of AIS or transient ischemic attacks. 3. The combination of edaravon (Ksavron) and citicoline (Neurocytin) as part of comprehensive therapy allows to each the advanced protection of the neurovascular unit in AIS.
New Approaches in Nanomedicine for Ischemic Stroke
