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Sedative and Analgesic Pharmacokinetics During Pediatric ECMO.

ABSTRACT: Sedatives and analgesics are often administered to critically ill children supported by extracorporeal membrane oxygenation (ECMO) to facilitate comfort and to decrease risks of life-threatening complications. Optimization of sedative and analgesic dosing is necessary to achieve desired therapeutic benefits and must consider interactions between the circuit and patient that may affect drug metabolism, clearance, and impact on target organs. This paper reviews existing in vitro and pediatric in vivo literature concerning the effects of the ECMO circuit on sedative and analgesic disposition and offers dosing guidance for the management of critically ill children receiving these drugs.

SUBMITTER: Zimmerman KO

PROVIDER: S-EPMC7671016 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Sedative and Analgesic Pharmacokinetics During Pediatric ECMO.

Zimmerman Kanecia O KO Dallefeld Samantha H SH Hornik Christoph P CP Watt Kevin M KM

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 20201113 8

Sedatives and analgesics are often administered to critically ill children supported by extracorporeal membrane oxygenation (ECMO) to facilitate comfort and to decrease risks of life-threatening complications. Optimization of sedative and analgesic dosing is necessary to achieve desired therapeutic benefits and must consider interactions between the circuit and patient that may affect drug metabolism, clearance, and impact on target organs. This paper reviews existing <i>in vitro</i> and pediatr ...[more]

PMID: 33214778

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Project description:BackgroundProviding analgesia and sedation is an essential component of caring for many mechanically ventilated patients. The selection of analgesic and sedative medications during the COVID-19 pandemic, and the impact of these sedation practices on patient outcomes, remain incompletely characterized.Research questionWhat were the hospital patterns of analgesic and sedative use for patients with COVID-19 who received mechanical ventilation (MV), and what differences in clinical patient outcomes were observed across prevailing sedation practices?Study design and methodsWe conducted an observational cohort study of hospitalized adults who received MV for COVID-19 from February 2020 through April 2021 within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. To describe common sedation practices, we used hierarchical clustering to group hospitals based on the percentage of patients who received various analgesic and sedative medications. We then used multivariable regression models to evaluate the association between hospital analgesia and sedation cluster and duration of MV (with a placement of death [POD] approach to account for competing risks).ResultsWe identified 1,313 adults across 35 hospitals admitted with COVID-19 who received MV. Two clusters of analgesia and sedation practices were identified. Cluster 1 hospitals generally administered opioids and propofol with occasional use of additional sedatives (eg, benzodiazepines, alpha-agonists, and ketamine); cluster 2 hospitals predominantly used opioids and benzodiazepines without other sedatives. As compared with patients in cluster 2, patients admitted to cluster 1 hospitals underwent a shorter adjusted median duration of MV with POD (β-estimate, -5.9; 95% CI, -11.2 to -0.6; P = .03).InterpretationPatients who received MV for COVID-19 in hospitals that prioritized opioids and propofol for analgesia and sedation experienced shorter adjusted median duration of MV with POD as compared with patients who received MV in hospitals that primarily used opioids and benzodiazepines.

Project description:BACKGROUND:Midazolam premedication is widely used before general anesthesia, but lacks clinical evidence of effectiveness. The present study aimed to evaluate the effectiveness of midazolam premedication following 4 aspects: anxiety reduction, sedation, hemodynamic stabilization, and analgesia. METHODS:In a randomized, single-blind, prospective study, a total of 128 women were allocated to the midazolam premedication group (Group P, n?=?64) or the control group (Group N, n?=?64). The patients were asked to complete the Beck anxiety inventory (BAI) 2 times: on the day before surgery (BS) and 30?minutes after midazolam premedication (T0). Depth of anesthesia using state entropy (SE), conventional hemodynamic data using heart rate (HR) and mean blood pressure (MBP), and analgesic profiles using surgical pleth index (SPI) were acquired at the following 4 points: T1-pre-induction, T2-prior to intubation, T3-intubation, and T4-20?minutes after intubation. RESULTS:No change in BAI score was observed between BS and T0 in both groups P and N (median and interquartile range [IQR], Group P: BS-4.5 [2.0-7.0], T0-4.0 [1.0-9.0], P?=?.603; Group N: BS-4.0 [1.0-8.5], T0-3.5 [1.0-6.0], P?=?.066). Midazolam premedication reduced SE at T2-4 (mean difference with 95% confidence interval [95% CI], T2-7.1 [1.6-12.6], P?=?.012; T3-10.4 [6.5-14.4], P?<?.001; T4-9.2 [5.0-13.4], P?<?.001). Midazolam premedication also reduced HR (mean differences [95% CI], T1-7.3 [2.5-12.1], P?=?.003; T3-6.6 [1.1-12.2], P?=?.020) and MBP at T1 and T3 (mean differences [95% CI], T1-7.3 [2.5-12.1], P?=?.003; T3-8.6 [1.3-15.9], P?=?.021), and lowered SPI at T1-3 (mean differences [95% CI]: T1-12.7 [6.1-19.4], P?<?.001; T2-6.0 [0.5-11.5], P?=?.033; T3-7.9 [1.7-14.1], P?=?.012). CONCLUSION:Midazolam premedication did not reduce the level of anxiety. However, midazolam premedication reduced the entropy values, stabilized hemodynamics, and provided analgesia during the induction of anesthesia. The purpose of midazolam premedication needs to be reconsidered.

Project description:BackgroundInflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO.MethodsWe conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ], interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course.ResultsAll ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs. normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition.ConclusionsHigh levels of circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO.ImpactThe inflammatory, endothelial activation, and fibrinolytic profile of children on ECMO differs by primary indication for extracorporeal support. Proinflammatory biomarkers on ECMO day 1 are associated with abnormal neurologic imaging in children on ECMO in univariable but not multivariable models. In multivariable models, a pronounced proinflammatory and prothrombotic biomarker profile on ECMO day 1 and longitudinally was significantly associated with mortality. Further studies are needed to identify inflammatory, endothelial, and fibrinolytic profiles associated with increased risk for neurologic injury and mortality through potential mediation of bleeding and thrombosis.

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Sedative and Analgesic Pharmacokinetics During Pediatric ECMO.

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Sedative and Analgesic Pharmacokinetics During Pediatric ECMO.

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