Augmented renal clearance (ARC) is a manifestation of enhanced renal function seen in critically ill patients. The use of regular unadjusted doses of renally eliminated drugs in patients with ARC might lead to therapy failure. The purpose of this scoping review was to provide and up-to-date summary of the available evidence pertaining to the phenomenon of ARC. A literature search of databases of available evidence in humans, with no language restriction, was conducted. Databases searched were MEDLINE (1946 to April 2017), EMBASE (1974 to April 2017) and the Cochrane Library (1999 to April 2017). A total of 57 records were included in the present review: 39 observational studies (25 prospective, 14 retrospective), 6 case reports/series and 12 conference abstracts. ARC has been reported to range from 14 to 80%. ARC is currently defined as an increased creatinine clearance of greater than 130 mL/min/1.73 m2 best measured by 8–24 h urine collection. Patients exhibiting ARC tend to be younger (<50 years old), of male gender, had a recent history of trauma, and had lower critical illness severity scores. Numerous studies have reported antimicrobials treatment failures when using standard dosing regimens in patients with ARC. In conclusion, ARC is an important phenomenon that might have significant impact on outcome in critically ill patients. Identifying patients at risk, using higher doses of renally eliminated drugs or use of non-renally eliminated alternatives might need to be considered in ICU patients with ARC. More research is needed to solidify dosing recommendations of various drugs in patients with ARC.

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Status epilepticus (SE) is a medical emergency that is associated with a significant morbidity and mortality. Recently, there has been significant interest in the use of ketogenic diets (KD) in the management of SE. KD is a high‐fat, low‐carbohydrate, and adequate protein diet that has been shown to be a safe and effective adjuvant to present SE management in patients with refractory epilepsy. Many case reports and case series have demonstrated the potential safety and effectiveness of KD for the acute treatment of SE; however, quality studies remain scarce on this topic. The purpose of this systematic review is to summarize the available evidence for the safety and effectiveness of KD in adults with SE. A literature search was performed in MEDLINE, EMBASE, Cochrane Library, and CINAHL (September 14, 2018). The search was repeated on March 27, 2019, to include any studies published since the original search. Keywords related to KD and SE were used. Studies were selected based on the reported use of the KD in SE. The search resulted in a total of 954 records. After screening and full‐text review, 17 articles were included in this review: four observational studies, 10 case reports, and 3 case series. Based on the observational studies, a total of 38 Patients with SE have been reported. KD was successful in achieving cessation of SE in 31 Patients (82%). The most common adverse effects reported were metabolic acidosis, hyperlipidemia, and hypoglycemia. The current limited evidence suggests that KD might be considered as an option for adult patients with SE. Although promising, the results need to be interpreted with caution due to the inherent bias, confounding and small sample size of the included studies. A randomized controlled trial is recommended to establish role of KD in the management of SE in adults.

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Routine TDM of levetiracetam is not recommended for all populations, however, it may be beneficial to maintain an individual therapeutic range in patients where the PK of LEV may be altered, such as in patients who are critically ill patients, pregnant, pediatrics or elderly.

Continuous renal replacement therapy (CRRT) is used for managing acute kidney injury in critically ill patients. Removal of antiepileptic drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay. The objective of the current review was to summarize the available evidence for AED removal by CRRT. An electronic literature search of PubMed (1946 to May 2016), Medline (1946 to May 2016), and Embase (1974 to May 2016) databases for studies discussing AED removal by CRRT was conducted. A total of 31 case reports discussing 32 patients were found. AEDs reported were levetiracetam (n = 3), valproic acid (n = 9), carbamazepine (n = 10), phenytoin (n = 3), phenobarbital (n = 4), lacosamide (n = 1), gabapentin (n = 1), and topiramate (n = 1). Two-thirds of the reports were about using CRRT in drug overdose and one-third was about AED removal by CRRT during therapy. Based on the current limited evidence and pharmacokinetic characteristics of AEDs, renally eliminated AEDs and/or AEDs with limited protein binding such as levetiracetam are more likely to be removed by CRRT than AEDs that are mainly metabolized and extensively protein bound such as carbamazepine. In conclusion, there is not enough evidence to provide robust dosing recommendations for AEDs in patients undergoing CRRT. Further studies are needed.

Nimodipine has been shown to improve outcomes following aneurysmal subarachnoid hemorrhage. Guidelines recommend that all patients receive a fixed dose of oral nimodipine for 21 days. However, pharmacokinetic studies have suggested variability of nimodipine pharmacokinetics in subarachnoid hemorrhage and in other patient populations. The clinical relevance of such variability is unknown. Therefore, the objective of the present review is, first, to conduct a literature review and summarize nimodipine pharmacokinetic data and sources of variability in various patient groups. Second, to determine if there is any evidence reporting an association between nimodipine exposure and clinical outcomes in patients with subarachnoid hemorrhage. A systematic literature search was performed in MEDLINE and EMBASE. The following keywords were used: ("nimodipine" OR "nymalize" OR "nimotop") AND ("pharmacokinetic*", OR "PK"). The search results were limited to English language and human studies. A large interpatient variability in nimodipine pharmacokinetics has been reported. Patient-specific factors that had an influence on pharmacokinetic parameters are age, comorbidities, variabilities in metabolism due to genetic polymorphism and co-administered medications, as well as nimodipine administration technique. The association between nimodipine exposure and clinical outcomes remains unclear and data available are too scarce to reach a firm conclusion. Here, we present a narrative review with a systematic literature search discussing nimodipine pharmacokinetic variability in various patient populations. It is not clear if minimal or lack of systemic exposure to nimodipine denies its benefit and contributes to worsening outcomes in patients with subarachnoid hemorrhage. Further studies are needed to determine if such an association exists. Key Points Nimodipine exposure is highly variable among individuals. Age, liver disease, genetic make-up, and nimodipine administration techniques influence nimodipine exposure.