Browsing by Author "Lee, Jan Hau"

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    Association between simulated ketamine exposures and oxygen saturations in children.
    (International journal of pharmacokinetics, 2023-02) Commander, Sarah Jane; Gonzalez, Daniel; Kumar, Karan R; Spears, Tracy; Cohen-Wolkowiez, Michael; Zimmerman, Kanecia O; Lee, Jan Hau; Hornik, Christoph P

    Aim

    We performed a real-world data analysis to evaluate the relationship between simulated ketamine exposures and oxygen desaturation in children.

    Materials & methods

    A previously developed population pharmacokinetic model was used to simulate exposures and evaluate target attainment, as well as the association with oxygen desaturation in children ≤17 years treated with intravenous ketamine.

    Results

    In 2022 children, there was no significant association between simulated plasma ketamine concentrations and oxygen saturation; however, a higher cumulative area under the curve was associated with increased odds of progression to significant desaturation (<85%), though magnitude of effect was small.

    Conclusion

    By leveraging a population pharmacokinetic model and real-world data, we confirmed there is no relationship between simulated ketamine plasma concentration and oxygen desaturation.
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    Nutrition in Pediatric Extracorporeal Membrane Oxygenation: A Narrative Review.
    (Frontiers in nutrition, 2021-01) Toh, Theresa SW; Ong, Chengsi; Mok, Yee Hui; Mallory, Palen; Cheifetz, Ira M; Lee, Jan Hau
    Extracorporeal membrane oxygenation (ECMO) support is increasingly utilized in quaternary pediatric intensive care units. Metabolic derangements and altered nutritional requirements are common in critically ill children supported on ECMO. However, there remains no consensus on the optimal approach to the prescription of nutrition in these patients. This narrative review aims to summarize the current medical literature on various aspects of nutrition support in pediatric patients on ECMO. These include: (1) nutritional adequacy, (2) pros and cons of feeding on ECMO, (3) enteral vs. parenteral nutrition, and (4) proposed recommendations and future directions for research in this area.
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    Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review.
    (Frontiers in pediatrics, 2020-01) Sutiman, Natalia; Koh, Janine Cynthia; Watt, Kevin; Hornik, Christoph; Murphy, Beverly; Chan, Yoke Hwee; Lee, Jan Hau
    Objectives: This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. Data Sources: We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to "ECMO" and "pharmacokinetics," "pharmacology," "drug disposition," "dosing," and "pediatrics." Study Selection: Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Data Extraction: Clearance and/or volume of distribution values were extracted from included studies. Data Synthesis: Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials (n = 13) and anticonvulsants (n = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25-455% increase relative to non-ECMO controls). Conclusions: There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations. Trial Registration Prospero Identifier: CRD42019114881.