Therapeutic drug monitoring has gained much attention in the management of immunosuppressive therapy. Area under the plasma drug concentration-time curve (AUC) is the pharmacokinetic (PK) parameter most commonly used to assess total exposure to a drug. However, estimation of AUC requires multiple blood samples throughout the dosing period, which is often inconvenient and expensive. Limited sampling strategies (LSSs) are therefore developed to estimate AUC and other PK parameters accurately and precisely while minimizing the number of blood samples needed. This greatly reduces costs, labor and inconvenience for both patients and clinical staff. In the therapeutic management of solid organ transplantation, LSSs for cyclosporine are commonplace and have been extensively reviewed. Thus, this systematic review paper focuses on other immunosuppressive agents and categorizes the 24 pertinent citations according to the U.S. Preventive Services Task Force rating scale. Thirteen articles (3 level I, 1 level II-1, 2 level II-2, and 7 level III) involved LSSs for mycophenolate, 7 citations (1 level I and 6 level III) for tacrolimus (TAC), and 3 citations (all level III) for other drugs (sirolimus) or multiple drugs. The 2 main approaches to establishing LSSs, multiple regression and Bayesian analyses, are also reviewed. Important elements to consider for future LSS studies, including proper validation of LSSs, convenient sampling times, and application of LSSs to the appropriate patient population and drug formulation are discussed. Limited sampling strategies are a useful tool to help clinicians make decisions on drug therapy. However, patients' pathophysiology, environmental and genetic factors, and pharmacologic response to therapy, in conjunction with PK profiling tools such as LSSs, should be considered collectively for optimal therapy management.

This study confirms the high dialyzability of both acetaminophen and acetylcysteine. Hemodialysis appears to be a beneficial therapeutic option in cases of massive acetaminophen ingestion with coma and lactic acidosis. Additionally, these results suggest that the infusion rate of acetylcysteine must be more than double during hemodialysis to compensate for its ongoing removal and provide similar plasma concentrations to the usual acetylcysteine regimen.

No abstract

Objective: Although anecdotal reports suggest that intravenous lipid emulsion (ILE) therapy is effective in a large variety of overdoses, the few controlled human trials published to date yielded disappointing results. Because of potential publication biases, there are few reports concerning the failure of ILE. The primary aim of this study was to identify fatal poisoning cases in the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS) in which ILE was administered. Methods: We obtained an approved release of data from NPDS for years 2010-2015 in which the words "lipid," "ILE," or "fat" appeared in the narrative. Duplicate cases were excluded as were cases in which ILE was not clearly given. Case data were extracted by one author using a predetermined tool, and the information was confirmed by a second author. The timing of ILE administration was characterized into one of four categories: cardiac arrest, first line, last resort, or part of multiple therapies given simultaneously. Response to ILE and adverse events was recorded. Results: Of the 826 cases retrieved from NPDS, 459 met final inclusion criteria. Over 50% of included cases involved either a calcium channel blocker or a beta-adrenergic antagonist. Of note, less than 25% of cases involved a substance for which the Lipid Emulsion Working Group found evidence to support its use. Most often, ILE was given along with multiple therapies (277 cases) or as a last resort (137 cases). In 127 cases, ILE was given during cardiac arrest. ILE was used as first line therapy in 34 cases. Response rates were reported as follows: no response (45%), unknown response (38%), transient/minimal response (7%), ROSC (7%), and immediate worsening (3%). Possible adverse reactions included: ARDS in 39 patients, lipemia causing a delay in laboratory evaluation in three cases, lipemia causing failure of a CRRT filter in two cases, worsening or new onset seizure in two cases, asystole immediately after administration in two cases, and fat embolism in one case. Conclusion: Within the Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS), hundreds of cases exist in which ILE therapy was given and death occurred. In many of these cases, ILE was given prior to cardiovascular collapse. Although there is some suggestion of transient improvement in a small subset of cases, adverse effects are also reported. When taken in totality, the number of published cases of failed lipid emulsion therapy outnumbers the published instances of ILE success. Given all the uncertainty generated by case reports, the evaluation of the role and efficacy of ILE therapy in non-local anesthetic poisoning needs robust controlled clinical trials.

No abstract