BACKGROUND AND PURPOSE: Suboptimal platelet inhibition by clopidogrel (clopidogrel resistance) may be associated with high rates of stent thrombosis and ischemic events. Our objective was to determine if ticagrelor, a P2Y 12 receptor inhibitor, can result in platelet inhibition in patients with clopidogrel resistance. METHODS: A thromboelastography-platelet mapping assay was used in all patients undergoing neuroendovascular procedures requiring oral clopidogrel. In patients with suboptimal platelet inhibition (<60%) on clopidogrel, ticagrelor was imitated after an oral bolus of 180 mg followed by 90 mg twice daily and the platelet mapping assay was repeated. The primary endpoint was hemorrhagic complications classified as major (hemoglobin decrease >5 g/dL or intracranial hemorrhage with deficits), minor (hemoglobin decrease 3-5 g/dL or intracranial hemorrhage without residual deficits), or insignificant. RESULTS:Suboptimal platelet inhibition on clopidogrel was seen in 70 of 106 patients undergoing neuroendovascular procedures. There was a significantly higher magnitude of platelet inhibition with ticagrelor compared with clopidogrel in patients with clopidogrel resistance (mean ± SD: 85.90 ± 10.74% vs. 29.26 ± 17.71%; P < .001); 50 of 70 patients showed optimal inhibition. Two patients had major (fatal) hemorrhagic events (both received either intravenous thrombolytics and/or eptifibatide infusion). Three patients had minor hemorrhagic events, and two patients had insignificant hemorrhagic events. Four of seven hemorrhagic events occurred in patients with optimal response to clopidogrel, two occurred in patients with suboptimal response to ticagrelor, and one occurred in a patient with optimal response to ticagrelor. CONCLUSIONS: Oral ticagrelor can augment platelet inhibition in patients who have clopidogrel resistance.

No abstract

Hypertriglyceridemia and related pancreatitis due to the use of lipid emulsions such as propofol has been documented, but less is known about the additive adverse effects of propofol and clevidipine lipid emulsions in the literature. We report an unusual case, highlighting the trend of serum triglyceride and pancreatic enzymes (amylase/lipase) with the administration of propofol and clevidipine for a prolonged period in the neurocritical care setting. We present a case of a 27-year-old male who was admitted to the neuroscience intensive care unit (NSICU) for management of severe subarachnoid hemorrhage (SAH) with six-millimeter (mm) midline shift to the left from the rupture of anterior communicating artery aneurysm. The patient was given propofol infusion to maintain sedation and manage intracranial pressures, and clevidipine was chosen over other antihypertensive class for blood pressure management secondary to renal impairment. To focus on the risk of hypertriglyceridemia and associated pancreatitis with the combined use of lipid emulsions we quantified the effect of lipid emulsions on serum triglycerides. We calculated the total calorie and fat content the patient received from the propofol and clevidipine along with the calorie intake from enteral nutrition (Fibersource® tube feed). The patient received a total propofol infusion of 44,391.2 milligrams (mg) over 16 days which accounts for 4,882.99 kilocalories (kcal) and 443.91 grams of fat. He received a total clevidipine infusion of 297 mg over the 48-hour period which contributes 594 kcal and 59.4 grams of fat. The required daily calorie intake through enteral nutrition of Fibresource® was titrated to a goal of 80 mL/hour which provided 2,304 kcal and 76.8 grams of fat each day. We also graphically depicted the rise in the serum triglyceride level after continuous infusion of propofol and clevidipine and subsequent improvement in the amylase and lipase level after the propofol was discontinued. Hence we conclude, careful and periodic monitoring of the serum triglyceride levels and limitation on the total calories from other fat sources such as enteral nutrition can help to mitigate the drug-induced effects.

Introduction: Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and associated cerebral ischemia and improve outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH) due to its anti-platelet, anti-proliferative, and vasodilatory effects. Due to recent publication of randomized controlled clinical trials, a meta-analysis was performed to identify the common treatment effect. Methods: We performed a meta-analysis of four randomized controlled clinical trials. The primary endpoint of interest was cerebral ischemia related to vasospasm. Secondary endpoints were angiographic vasospasm, new cerebral infarct, mortality, and death or disability at the 90 days following randomization. Using random-effects models with study as a random effect, relative risks (RR) and 95% confidence intervals (CI) were generated Results: A total of 405 subjects (200 randomized to oral cilostazol 100 mg twice per day) were included in the meta-analysis. The proportion of subjects with cerebral ischemia related to vasospasm was significantly lower in those who were assigned to cilostazol treatment (RR 0.46; 95% CI 0.21-1.00; p< 0.050) without any heterogeneity between the trials (Cochran’s Q statistic 1.52, df 2; P = .468, I 2 =0.0%). The proportion of subjects who had new cerebral infarction was significantly lower in subjects who were assigned to cilostazol treatment (RR 0.40, 95% CI 0.32-0.49, p=0.0009). There was a lower rate of death or disability at 90 days in subjects who were assigned to cilostazol treatment (RR 0.44, 95% 0.28-0.70, p=0.011) without any heterogeneity between the trials (Cochran’s Q statistics 1.49, df 3; P = .685, I 2 =0.0%). The proportion of subjects who had any adverse events was not significantly different in subjects who were assigned to cilostazol treatment (RR 1.24, 95% 0.68-2.25, p=0.26). Conclusion: The reduction in rates of cerebral ischemia related to vasospasm and death or disability at follow-up support further evaluation of oral cilostazol in patients with aSAH in a phase III large randomized clinical trial.

No abstract