Neurocritical care
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The sulfonylurea receptor 1 (Sur1)-transient receptor potential 4 (Trpm4) channel is an important molecular element in focal cerebral ischemia. The channel is upregulated in all cells of the neurovascular unit following ischemia, and is linked to microvascular dysfunction that manifests as edema formation and secondary hemorrhage, which cause brain swelling. Activation of the channel is a major molecular mechanism of cytotoxic edema and "accidental necrotic cell death." Blockade of Sur1 using glibenclamide has been studied in different types of rat models of stroke: (i) in conventional non-lethal models (thromboembolic, 1-2 h temporary, or permanent middle cerebral artery occlusion), glibenclamide reduces brain swelling and infarct volume and improves neurological function; (ii) in lethal models of malignant cerebral edema, glibenclamide reduces edema, brain swelling, and mortality; (iii) in models with rtPA, glibenclamide reduces swelling, hemorrhagic transformation, and death. ⋯ Here, we provide a comprehensive review of the basic science, preclinical experiments, and retrospective clinical studies on glibenclamide in focal cerebral ischemia and stroke. We also compare the preclinical work in stroke models to the updated recommendations of the Stroke Therapy Academic Industry Roundtable (STAIR). The findings reviewed here provide a strong foundation for a translational research program to study glibenclamide in patients with ischemic stroke.
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Multicenter Study
Predictors of Severe Hypotension in Neurocritical Care Patients Sedated with Propofol.
Propofol is used extensively in neurocritical care (NCC) due to its pharmacologic properties allowing for facilitation of serial neurologic examinations. Despite widespread use, few studies have identified risk factors for hypotension in these patients. We aimed to determine predictors of hypotension in NCC patients sedated with propofol. ⋯ Multiple factors predicted hypotension in NCC patients receiving propofol. Clinicians should use propofol cautiously in patients with a lower baseline MAP or receiving RRT. Development of protocols related to the frequency of dose titrations is also recommended to prevent this avoidable complication.
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Transcranial Doppler (TCD) is widely used to detect and follow up cerebral vasospasm after subarachnoid hemorrhage (SAH). Therapeutic hypothermia might influence blood flow velocities assessed by TCD. The aim of the study was to evaluate the effect of hypothermia on Doppler blood flow velocity after SAH. ⋯ Therapeutic hypothermia after SAH decreases Doppler blood flow velocity in both intracranial hypertension and DCI cases. The results can be the effect of hypothermia-related mechanisms or resolving cerebral vasospasm during prolonged hypothermia.
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Observational Study
Differential Disruption of Blood-Brain Barrier in Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) is a significant cause of death and disability in young adults, but not much is known about the incidence and characteristics of blood-brain barrier (BBB) dysfunction in this group. In this proof of concept study, we sought to quantify the incidence of BBB dysfunction (defined as a cerebrospinal fluid (CSF)-plasma albumin quotient of ≥0.007) and examine the relationship between plasma and CSF levels of proteins and electrolytes, in patients with severe TBI. ⋯ In summary, passive BBB dysfunction is common in patients with severe TBI, and may have important implications for effectiveness of osmotherapy and long-term outcomes. Also, our results suggest that the CSF-plasma total protein quotient, a measurement which is readily available, can be used instead of the CSF-plasma albumin quotient for evaluating BBB dysfunction.
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General anesthesia (GA) for acute stroke interventions may be associated with inferior functional outcomes. Our goal was to identify physiologic parameters that mediate this association. ⋯ While BP decreased significantly in patients undergoing GA for acute stroke intervention, it did not correlate with patient outcome. Decreases in ETCO2 at 30 and 60 min, however, were associated with 90-day mRS.