BackgroundThe incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity. This may be even more challenging with the availability of newer antiepileptics where the evidence for their use in critically ill patients is limited.Main bodyThis article reviews the pharmacokinetics and pharmacodynamics of antiepileptics as well as application of these principles when dosing antiepileptics and monitoring serum levels in critically ill patients. The selection of the most appropriate anticonvulsant to treat seizure and status epileptics as well as the prophylactic use of these agents in this setting are also discussed. Drug-drug interactions and the effect of nonpharmacological interventions such as renal replacement therapy, plasma exchange, and extracorporeal membrane oxygenation on anticonvulsant removal are also included.ConclusionOptimal management of antiepileptic drugs in the intensive care unit is challenging given altered physiology, polypharmacy, and nonpharmacological interventions, and requires a multidisciplinary approach where appropriate and timely assessment, diagnosis, treatment, and monitoring plans are in place.
Atypical antipsychotics initiated in the ICU are frequently continued after hospital discharge. Given the known risks associated with extended therapy, initiatives are needed to prevent inappropriate continuation.
Status epilepticus (SE) has a high mortality rate and is one of the most common neurologic emergencies. Fast progression of this neurologic emergency and lack of response to traditional antiepileptic drugs (AEDs) in most cases has challenged clinicians to use new agents. This article evaluates the efficacy and safety of AEDs released to the market after 2000 for SE, refractory status epilepticus (RSE), and super‐refractory status epilepticus (SRSE). The PubMed database was searched for clinical trials published between January 2000 and July 2018 using the search terms status epilepticus, refractory status epilepticus, super refractory status epilepticus, brivaracetam, clobazam, cannabidiol, eslicarbazepine, lacosamide, perampanel, rufinamide, stiripentol, and zonisamide. Trials that evaluated these agents in adults with SE, RSE, and SRSE were included. Brivaracetam use was identified in two retrospective reviews with success rates of 27% and 57%. One unsuccessful case report of cannabidiol use in SE was found. Four clobazam studies were identified in SE and RSE with success rates ranging from 25–100%. No evidence for the use of eslicarbazepine and zonisamide was found. Using the search terms for lacosamide identified 38 articles: 1 systematic review, 5 prospective studies, 15 retrospective reviews, and 17 case reports. Success rates and dosing varied, but studies that included focal or partial types of SE showed higher success rates. Five articles were identified regarding perampanel use in this setting. Three were retrospective reviews with success rates ranging from 17–60%, and two were case reports. Only one case report regarding the use of rufinamide was found; rufinamide titrated up to 4.4 mg/day allowed discontinuation of barbiturate and clobazam. One case report and two case series of stiripentol were found with reported efficacy between 60% and 100% in SRSE. Evidence is currently insufficient to support the use of these agents in this setting.
Background: Intra- and postprocedural thrombosis are major complication of aneurysmal coil embolization, stent-assisted coiling, and pipeline embolization. The common but unproven practice of dual antiplatelet therapy with aspirin and a P2Y12 inhibitor in neuro-endovascular patients is inferred from the cardiology literature without large clinical trials to support it in neuro-endovascular patients. Objective: We conducted an electronic survey to identify practice variations surrounding the use of oral antiplatelets in patients undergoing endovascular neuro-interventional procedures across neuro-endovascular centers in the United States. Methods: An electronic survey was distributed via the Web. Any practicing neuro-intensive care unit (ICU), neuro-interventional or stroke physician, pharmacist, physician assistant, or nurse practitioner was eligible to respond to this survey between June and October 2017. Results: A total of 33 responses were collected during the survey period. A response rate of 16% was calculated after taking into account all comprehensive stroke centers in the United States. Aspirin and clopidogrel was the standard-of-care antiplatelet regimen utilized in the majority of institutions (82%). Alternatively, 4 institutions used monotherapy (aspirin [n = 2], clopidogrel [n = 1], either aspirin or clopidogrel [n = 1]) and 2 institutions reported practitioner-dependent practices. Just under half of the centers reported ticagrelor as the primary alternative in clopidogrel nonresponders (48%). Conclusion: Dual antiplatelet therapy with aspirin and clopidogrel appears to be standard of care in this setting based on our survey. About half of responding institutions use ticagrelor in cases where clopidogrel resistance is suspected. Large society-wide patient registries are needed to provide data for future safety and efficacy studies.
The purpose of this analysis is to assess the effect of antiepileptics (AEDs) on seizure prevention and short and long term functional outcomes in patients with acute intracerebral hemorrhage. Method: The meta-analysis was conducted using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochrane Library, and EMBASE databases. Search terms included "Anticonvulsants", "Intracerebral Hemorrhage", and related subject headings. Articles were screened and included if they were fulltext and in English. Articles that did not perform multivariate regression were not included. Overall effect size was evaluated with forest plots and publication bias was assessed with the Begg's and Egger's tests. Results: A total of 3912 articles were identified during the initial review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. No significant association between the use of AEDs after ICH and functional outcome (OR 1.53 [95%CI: 0.81-2.88] P = 0.18, I 2 = 81.7%). Only one study evaluated the effect AEDs had in preventing post-ICH seizures. Conclusions: The use of prophylactic AEDs was not associated with improved short and long outcomes after acute ICH. This analysis supports the 2015 AHA/ASA recommendation against prophylactic AEDs (class III; level of evidence b).
In an era of increasing attention to patient satisfaction mitigated by growing concerns over the harms imposed by opioids, alternative analgesic therapies are being investigated with promising results.
Our findings highlight the unpredictable PK of voriconazole and reinforce the importance of continuous therapeutic drug monitoring in critically ill patients.
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