Cilostazol is a phosphodiesterase III inhibitor which increases cAMP and leads to reversible inhibition of platelet aggregation, vasodilation and inhibition of vascular smooth muscle cell proliferation. A systematic review was recently published in the Journal of Neurology on the effect of cilostazol on the incidence of delayed cerebral ischemia in subarachnoid hemorrhage (Department of Neurosurgery, West China Hospital).
The meta-analysis included seven studies, all of which were done in Japan: three were randomized controlled studies, 3 were retrospective studies and one was a prospective study. Most studies used cilostazol at 200mg per day for 14 days.
Forest plots for the outcomes provided below:
A. Severe angiographic vasospasm
B. Symptomatic vasospasm
C. New cerebral infarction
D. Poor outcome
Adverse effects related to cilostazol administration in the studies include diarrhea, transaminitis, tachycardia, headaches, hemorrhagic and cardiac events.
The meta-analysis concluded that cilostazol effectively reduced the incidence of severe angiographic vasospasm, symptomatic vasospasm, new cerebral infarction and poor outcome in patients with aneurysmal subarachnoid hemorrhage, but does not reduce mortality significantly.
It is important to note that all of the studies included in the meta-analysis were from one country (Japan), which precludes the generalization of the results to the general population. Also, none of the patients in the studies received nimodipine, which has not been approved for SAH treatment in Japan. Whether or not the co-administration of nimodipine would add to or nullify the benefits seen with cilostazol requires further investigation.
Take home message: should not change current practice, needs further research.
Shan, T., Zhang, T., Qian, W., Ma, L., Li, H., You, C. and Xie, X. (2019). Effectiveness and feasibility of cilostazol in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Journal of Neurology.
Uptodate.com. (2019). UpToDate. [online] Available at: https://www.uptodate.com/contents/cilostazol-drug-information?sectionName=Adult&topicId=8872&search=cilostazol&usage_type=panel&anchor=F151445&source=panel_search_result&selectedTitle=1~36&kp_tab=drug_general&display_rank=1#F151413 [Accessed 6 Apr. 2019].
NSE is an enzyme in humans encoded by the ENO2 gene. It is a phosphopyruvate hydratase. This enzyme is found in mature neurons and cells of neuronal origin, and is released after neuronal damage.
NSE has been studied as a marker for brain injury. Serum levels have been shown to be elevated in patients with stroke, correlates with the infarct volume and the degree of neurologic deficit. However, increase in serum NSE after brain injury occur late and lack sensitity and specificity.
Enolase 2. (2019). Retrieved from https://en.wikipedia.org/wiki/Enolase_2
González-García, S., González-Quevedo, A., Peña-Sánchez, M., Menéndez-Saínz, C., Fernández-Carriera, R., & Arteche-Prior, M. et al. (2012). Serum neuron-specific enolase and S100 calcium binding protein B biomarker levels do not improve diagnosis of acute stroke. The Journal Of The Royal College Of Physicians Of Edinburgh, 42(3), 199-204. doi: 10.4997/jrcpe.2012.302
West Haven criteria for altered mental status in hepatic encephalopathy
Grade 0 Minimal hepatic encephalopathy, lack of detectable changes in personality or behavior; no asterixis.
Grade 1 Trivial lack of awareness, shortened attention span, sleep disturbance, altered mood, and slowing the ability to perform mental tasks; asterixis may be present.
Grade 2 Lethargy or apathy, disorientation to time, amnesia of recent events, impaired simple computations, inappropriate behavior, and slurred speech; asterixis is present.
Grade 3 Somnolence, confusion, disorientation to place, bizarre behavior, clonus, nystagmus, and positive Babinski sign; asterixis usually absent.
Grade 4 Coma, lack of verbal, eye, and oral response to stimuli.
Emergency Management in Neurocritical Care: Chapter 17 Metabolic Encephalopathies, by Edward Manno
Lenox Hill Hospital CAUTI Team.
LHH Pharmacy handouts
LHH Pharmacy handouts.