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OBJECTIVES: This study aimed to determine the oxygenator impact on alterations of remdesivir (RDV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane -oxygenation (ECMO) circuit including the Quadrox-i oxygenator. METHODS: One-quarter-inch and a 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A 1-time dose of RDV was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 0 to 5 minutes, and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-hour time points. The RDV was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-inch circuits with an oxygenator, there was a 35% to 60% RDV loss during the study period. For the 1/4-inch circuits without an oxygenator, there was a 5% to 20% RDV loss during the study period. For the 3/8-inch circuit with and without an oxygenator, there was a 60% to 70% RDV loss during the study period. CONCLUSIONS: There was RDV loss within the circuit during the study period and the RDV loss was more pronounced with the larger 3/8-inch circuit when compared with the 1/4-inch circuit. The impact of the -oxygenator on RDV loss appears to be variable and possibly dependent on the size of the circuit and -oxygenator. These preliminary data suggest RDV dosing may need to be adjusted for concern of drug loss via the ECMO circuit. Additional single- and multiple-dose studies are needed to validate these findings.

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BACKGROUND: To determine if receiving targeted antimicrobial (AM) prophylaxis has an effect on the rate of postoperative infections in patient's colonized with a multidrug resistant organism (MDRO) undergoing cardiothoracic surgery (CTS). METHODS: Single-center, retrospective medical record review of pediatric patients from birth to 18 years of age undergoing CTS from January 2013 to September 2018. Demographic data collected included age, specific MDRO, site of MDRO colonization, type of surgery, perioperative AM agent and type of infection. Patients were stratified into 2 groups, MDRO+ and MDRO-. Demographic and clinical characteristics were compared between groups with a Student's t test for continuous variables and a χ2, Fisher exact test or Mann-Whitney U test for noncontinuous variables. A 2-sided significance level of α = 0.05 was used to determine statistical significance. All analyses were performed using IBM SPSS Version 24 (SPSS Inc., Chicago, IL). RESULTS: Fifty patients (26 males/24 females) were included in the MDRO (+) group and 295 patients (168 males/127 females) in the MDRO (-) group. The median age was 0.48 years (interquartile range 0.24-1 year) and 0.9 years (interquartile range 0.19-8 years) in the MDRO (+) and MDRO (-) groups, P = 0.003. 2 of 50 (4%) MDRO (+) patients and 15 of 295 (5.1 %) MDRO (-) patients developed an infection, P = 1. 10 of 50 (20%) MDRO (+) patients received targeted AM toward the MDRO and none developed an infection. Of the 2 MDRO (+) patients with infection, 1 was infected with the MDRO. For MDRO (+) patients, there was no difference in the rate of infection whether targeted AM therapy was received, P = 1. CONCLUSIONS: There was no difference in the rate of postoperative infection between MDRO (+) and MDRO (-) patients. Additionally, these preliminary pediatric data suggest targeting AM agents to a specific MDRO does not impact the rate of postoperative infection in children undergoing CTS. Larger studies are warranted to confirm these findings.

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OBJECTIVES: To determine the oxygenator impact on alterations of ceftaroline in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation circuit including the Quadrox-i oxygenator (Maquet, Wayne, NJ). DESIGN: Quarter-inch and 3/8-inch, simulated closed-loop extracorporeal membrane oxygenation circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. An one-time dose of ceftaroline was administered into the circuits, and serial pre- and postoxygenator concentrations were obtained at 5 minutes, 1-, 2-, 3-, 4-, 5-, 6-, and 24-hour time points. Ceftaroline was also maintained in a glass vial, and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. SETTING: A free-standing extracorporeal membrane oxygenation circuit. PATIENTS: None. INTERVENTION: Single dose administration of ceftaroline into closed-loop extracorporeal membrane oxygenation circuits prepared with and without an oxygenator in series with serial preoxygenator, postoxygenator, and reference samples obtained for concentration determination over a 24-hour study period. MEASUREMENTS AND MAIN RESULTS: For the 1/4-inch circuit with an oxygenator, there was 79.8% drug loss preoxygenator and 82.5% drug loss postoxygenator at 24 hours. There was a statistically significant difference (p < 0.01) in the amount of ceftaroline remaining at 24 hours when compared with each prior time point for the 1/4-inch circuit. For the 1/4-inch circuit without an oxygenator, there was no significant drug loss at any study time point. For the 3/8-inch circuit with an oxygenator, there was 76.2% drug loss preoxygenator and 77.6% drug loss postoxygenator at 24 hours. There was a statistically significant difference (p < 0.01) in the amount of ceftaroline remaining at 24 hours when compared with each prior time point for the 3/8-inch circuit. For the 3/8-inch circuit without an oxygenator, there was no significant drug loss at any study time point. The reference ceftaroline concentrations remained relatively constant during the entire study period demonstrating the ceftaroline loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation and primarily the result of the oxygenator. CONCLUSIONS: This ex vivo investigation demonstrated significant ceftaroline loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours. Therapeutic concentrations of ceftaroline in the setting of extracorporeal membrane oxygenation may not be achieved with current U.S. Food and Drug Administration-recommended doses, and further evaluation is needed before specific drug dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

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OBJECTIVES: We sought to 1) evaluate how pediatricians approach situations in which families request continuation of organ support after declaration of death by neurologic criteria and 2) explore potential interventions to make these situations less challenging. DESIGN: A survey on management and personal experience with death by neurologic criteria was distributed electronically to pediatric intensivists and neurologists. We compared responses from individuals who practice in states with accommodation exceptions (accommodation states where religious or moral beliefs must be taken into consideration when declaring death: California, Illinois, New Jersey, New York) to those from non-accommodation states. SETTING: United States. SUBJECTS: The survey was opened by 254 recipients, with 186 meeting inclusion criteria and providing data about the region in which they practice; of these, 26% were from accommodation states. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: More than half of physicians (61% from both accommodation states and non-accommodation states) reported they cared for a pediatric patient whose family requested continuation of organ support after declaration of death by neurologic criteria (outside of organ donation; range, 1-17 times). Over half of physicians (53%) reported they would not feel comfortable handling a situation in which a pediatric patient's family requested care be continued after declaration of death by neurologic criteria. Nearly every physician (98%) endorsed that something needs to be done to make situations involving families who object to discontinuation of organ support after declaration of death by neurologic criteria easier to handle. Respondents felt that public education, physician education, and uniform state laws about these situations are warranted. CONCLUSIONS: It is relatively common for pediatricians who care for critically ill patients to encounter families who object to discontinuation of organ support after death by neurologic criteria. Management of these situations is challenging, and guidance for medical professionals and the public is needed.

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