Dataset Information

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: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:BackgroundAnalgesic, anti-inflammatory, and sedative drugs are available with potential side effects such as peptic ulcer and addiction among other things. In this regard, research is underway to find safe, effective, and economical drugs free of these side effects. In this study, an isolated natural product from Diospyros lotus, was tested for the aforementioned bioactivities.ObjectivesTo evaluate analgesic, anti-inflammatory, and sedative potential of D. lotus extracts in animal paradigms using BALB/c mice as experimental model.MethodsAnalgesic, anti-inflammatory and sedative activities of dinaphthodiospyrol G (1) isolated from the chloroform fraction of D. lotus were evaluated using different experimental procedures. Anti-inflammatory effect was evaluated using the carrageenan and histamine-induced paw edema, whereas the antinociceptive effect was quantified by means of the hot plate analgesiometer. On the other hand, the sedative effect was determined using animal assay for screening the locomotors effects of compound 1. Compound 1 was also subjected to molecular modeling studies against cyclooxygenase enzymes.ResultsResults from this investigation showed that the extract is devoid of anti-inflammatory and antinociceptive potentials but has a significant sedative effect, whereas the tested compound exhibited 55.23 and 78.34% attenuation in paw edema by carrageenan and histamine assays, respectively. A significant (p?<?0.001) and dose-dependent antinociceptive and sedative effects were demonstrated by the isolated compound. Molecular docking and dynamics simulation studies of the isolated compound against cyclooxygenase enzyme indicated that compound 1 forms specific interactions with key residues in the active site of the target receptor, which validates the potential use of the isolated compound as cyclooxygenase inhibitor.ConclusionsCompound 1 exhibited remarkable analgesic, anti-inflammatory, and sedative activities. These findings strongly justify the traditional use of D. lotus in the treatment of inflammation, pain, and insomnia.

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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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