scholarly journals Optimized Dosing Regimens of Meropenem in Septic Children Receiving Extracorporeal Life Support

2021 ◽  
Vol 12 ◽  
Author(s):  
Yixue Wang ◽  
Weiming Chen ◽  
Yidie Huang ◽  
Guangfei Wang ◽  
Zhiping Li ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Pediatric Intensive Care ◽  
Population Pharmacokinetic ◽  
Time Data ◽  
Mixed Effect ◽  
Nonlinear Mixed Effect Model ◽  
Nonlinear Mixed Effect ◽  
Dosing Regimens

Objectives: To develop a population pharmacokinetic model of meropenem in children with sepsis receiving extracorporeal life support (ECLS) and optimize the dosage regimen based on investigating the probability of target attainment (PTA).Methods: The children with sepsis were prospectively enrolled in a pediatric intensive care unit from January 2018 to December 2019. The concentration-time data were fitted using nonlinear mixed effect model approach by NONMEM program. The stochastic simulation considering various scenarios based on proposed population pharmacokinetics model were conducted, and the PTAs were calculated to optimize the dosage regimens.Results: A total of 25 children with sepsis were enrolled, of whom13 received ECMO, 9 received CRRT, and 4 received ECMO combined with CRRT. 12 children received a two-step 3-h infusion and 13 children received 1-h infusion. Bodyweight and creatinine clearance had significant impacts on the PK parameters. ECMO intervention was not related to the PK properties. If 100%T > MIC was chosen as target, children receiving 40 mg/kg q8h over a 3 h-infusion only reached the PTA up to 77.4%. If bacteria with MIC 2 mg/L were to be treated with meropenem and the PTA target was 50%T > MIC, a dose of 40 mg/kg q8h for 1 h infusion would be necessary.Conclusions: The PK properties of meropenem in septic children receiving extracorporeal life support were best described. We recommended the opitimized dosing regimens for septic children receiving ECLS depending on the PTA of PK target 50%T > MIC and 100%T > MIC, for children with sepsis during ECLS with different body weight, estimated creatinine clearance (eCRCL) and MIC of bacteria.

scholarly journals Population Pharmacokinetics of Arbekacin, Vancomycin, and Panipenem in Neonates

2004 ◽  
Vol 48 (4) ◽  
pp. 1159-1167 ◽  
Author(s):  
Toshimi Kimura ◽  
Keisuke Sunakawa ◽  
Nobuo Matsuura ◽  
Hiroaki Kubo ◽  
Shigehiko Shimada ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Serum Creatinine Level ◽  
Glomerular Filtration ◽  
Creatinine Level ◽  
Population Pharmacokinetic ◽  
Mixed Effect Model ◽  
Mixed Effect ◽  
Nonlinear Mixed Effect Model ◽  
Nonlinear Mixed Effect ◽  
Effect Model

ABSTRACT Immature renal function in neonates requires antibiotic dosage adjustment. Population pharmacokinetic studies were performed to determine the optimal dosage regimens for three types of antibiotics: an aminoglycoside, arbekacin; a glycopeptide, vancomycin; and a carbapenem, panipenem. Eighty-three neonates received arbekacin (n = 41), vancomycin (n = 19), or panipenem (n = 23). The postconceptional ages (PCAs) were 24.1 to 48.4 weeks, and the body weights (BWs) ranged from 458 to 5,200 g. A one-compartment open model with first-order elimination was applied and evaluated with a nonlinear mixed-effect model for population pharmacokinetic analysis. In the fitting process, the fixed effects significantly related to clearance (CL) were PCA, postnatal age, gestational age, BW, and serum creatinine level; and the fixed effect significantly related to the volume of distribution (V) was BW. The final formulas for the population pharmacokinetic parameters are as follows: CLarbekacin = 0.0238 × BW/serum creatinine level for PCAs of <33 weeks and CLarbekacin = 0.0367 × BW/serum creatinine level for PCAs of ≥33 weeks, V arbekacin = 0.54 liters/kg, CLvancomycin = 0.0250 × BW/serum creatinine level for PCAs of <34 weeks and CLvancomycin = 0.0323 × BW/serum creatinine level for PCAs of ≥34 weeks, V vancomycin = 0.66 liters/kg, CLpanipenem = 0.0832 for PCAs of <33 weeks and CLpanipenem = 0.179 × BW for PCAs of ≥33 weeks, and V panipenem = 0.53 liters/kg. When the CL of each drug was evaluated by the nonlinear mixed-effect model, we found that the mean CL for subjects with PCAs of <33 to 34 weeks was significantly smaller than those with PCAs of ≥33 to 34 weeks, and CL showed an exponential increase with PCA. Many antibiotics are excreted by glomerular filtration, and maturation of glomerular filtration is the most important factor for estimation of antibiotic clearance. Clinicians should consider PCA, serum creatinine level, BW, and chemical features when determining the initial antibiotic dosing regimen for neonates.

Elevated Serum Lactate Correlates With Intracranial Hemorrhage in Neonates Treated With Extracorporeal Life Support

PEDIATRICS ◽  
1995 ◽  
Vol 96 (5) ◽  
pp. 914-917
Author(s):  
Eva Nozik Grayck ◽  
Jon N. Meliones ◽  
Frank H. Kern ◽  
Doug R. Hansell ◽  
Ross M. Ungerleider ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Lactate Level ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Elevated Serum ◽  
Pediatric Intensive Care ◽  
Retrospective Chart Review ◽  
Serum Lactate ◽  
Platelet Counts ◽  
Lactate Levels

Objectives. To correlate the initial and maximal lactate levels with the occurrence of intracranial hemorrhage (ICH) and survival in patients treated with extracorporeal life support (ECLS). Design. Retrospective chart review. Setting. Pediatric intensive care unit. Patients. Eighty-two neonatal patients placed on ECLS for respiratory failure due to sepsis, meconium aspiration, or persistent pulmonary hypertension of the newborn. Measurements. The initial lactate level measured within 6 hours of initiating ECLS and the maximal lactate level measured throughout the ECLS course were collected. Lactate levels were described as mean lactate ± SE (mM). Head ultrasound reports and survival were reviewed. Platelet counts and activated clotting times (ACTs) were examined. Results. The mean initial and maximal lactate levels were higher in ECLS patients who developed ICH (initial: 10 ± 1.7 mM vs 6.4 ± 0.8 mM, p = .05 and maximal: 12.4 ± 2.5 mM vs 7.9 ± 0.8 mM, p = .04). Initial and maximal lactate levels were also elevated in nonsurvivors (initial: 11.7 ± 3 mM vs 6.4 ± 0.7 mM, p = .01 and maximal: 14.8 ± 3.3 mM vs 7.8 ± 0.8 mM, P &lt; .01). Platelet counts and ACT did not differ in patients with and without ICH. Conclusions. Lactate is a useful marker for the development of ICH in ECLS patients. In addition, elevated lactates during ECLS identify a subgroup of patients with poor outcome. Prospective studies are needed to determine whether the incorporation of this information into pre-ECLS and ECLS management will decrease the occurrence of ICH and improve survival.

scholarly journals ECMO em Recém-nascidos com Hérnia Diafragmática Congénita: A Experiência de um Centro de Referência de ECMO em Portugal

2020 ◽  
Vol 33 (12) ◽  
pp. 819
Author(s):  
Mariana Miranda ◽  
Francisco Abecasis ◽  
Sofia Almeida ◽  
Erica Torres ◽  
Leonor Boto ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Ventilatory Support ◽  
Pediatric Intensive Care ◽  
Cycle Duration ◽  
Extracorporeal Life Support Organization ◽  
Support Organization ◽  
Technological Advances

Introduction: The use of extracorporeal membrane oxygenation (ECMO) is considered by many authors as one of the most important technological advances in the care of newborns with congenital diaphragmatic hernia. The main objective of this study was to report the experience of a Portuguese ECMO center in the treatment of congenital diaphragmatic hernia.Material and Methods: Descriptive retrospective study of newborns with congenital diaphragmatic hernia requiring ECMO support in a Pediatric Intensive Care Unit from January 2012 to December 2019. Data collection using the Extracorporeal Life Support Organization registration and unit data base.Results: Fourteen newborns were included, all with left congenital diaphragmatic hernia, in a total of 15 venoarterial ECMO cycles. The median gestational age was 38 weeks and the median birth weight was 2.950 kg. Surgical repair was performed before entry into ECMO in six, during in seven and after in one newborn. The average age at placement was 3.3 days and the median cycle duration was 16 days. Prior to ECMO, all newborns had severe hypoxemia and acidosis despite optimized ventilatory support, with nitric oxide and inotropic therapy. After 24 hours on ECMO, there was correction of acidosis, improvement of oxygenation and hemodynamic stability. All cycles presented mechanical complications, the most frequent being the presence of clots in the circuit. The most frequent physiological complications were hemorrhagic and embolic (three newborns suffered an ischemic stroke during the cycle). Five newborns (35.7%) died, all associated with complications (two strokes, two massive bleedings and one accidental decannulation). Chronic lung disease, poor weight gain and psychomotor developmental delay were the most frequent long-term morbidities.Discussion: Despite technological advances in respiratory care and improved safety of the ECMO technique, the management of these newborns is complex and there are still several open questions, including the appropriate selection of patients, the best approach and time for surgical correction, and the treatment of pulmonary hypertension in the presence of persistent fetal shunts.Conclusion: Survival rate was higher than reported in 2017 Extracorporeal Life Support Organization report (64% versus 50%). Mechanical and hemorrhagic complications were very frequent.

scholarly journals Extracorporeal Membrane Oxygenation: The First 10 Years Experience of a Portuguese Pediatric Intensive Care Unit

2021 ◽  
Vol 34 (6) ◽  
pp. 435
Author(s):  
Daniel Meireles ◽  
Francisco Abecasis ◽  
Leonor Boto ◽  
Cristina Camilo ◽  
Miguel Abecasis ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Overall Survival ◽  
Intensive Care ◽  
Pediatric Intensive Care Unit ◽  
Pediatric Patients ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Pediatric Intensive Care ◽  
Overall Survival Rate ◽  
Clinical Complications

Introduction: In Portugal, extracorporeal membrane oxygenation (ECMO) is used in pediatric patients since 2010. The aim of this study was to describe the clinical characteristics of patients, indications, complications and mortality associated with the use of ECMO during the first 10-years of experience in the Pediatric Intensive Care Unit located in Centro Hospitalar Universitário Lisboa Norte.Material and Methods: Retrospective observational cohort study of all patients supported with ECMO in a Pediatric Intensive Care Unit, from the 1st of May 2010 up to 31st December 2019.Results: Sixty-five patients were included: 37 neonatal (≤ 28 days of age) and 28 pediatric patients (> 28 days). In neonatal cases, congenital diaphragmatic hernia was the main reason for ECMO (40% of neonatal patients and 23% of total). Among pediatric patients, respiratory distress was the leading indication for ECMO (47% of total). The median length of ECMO support was 12 days. Clinical complications were more frequent than mechanical complications (65% vs 35%). Among clinical complications, access site bleeding was the most prevalent with 38% of cases. The overall patient survival was 68% at the time of discharge (65% for neonatal and 71% for pediatric cases), while the overall survival rate in Extracorporeal Life Support Organization registry was 61%. The number of ECMO runs has been increasing since 2011, even though in a non-linear way (three cases in 2010 to 11 cases in 2019).Discussion: In the first 10 years we received patients from all over the country. Despite continuous technological developments, circuitrelated complications have a significant impact. The overall survival rate in the Pediatric Intensive Care Unit was not inferior to the one reported by the Extracorporeal Life Support Organization.Conclusion: The overall survival of our Pediatric Intensive Care Unit is not inferior to one reported by other international centers. Our experience showed the efficacy of the ECMO technique in a Portuguese centre.

scholarly journals Population Pharmacokinetic/Pharmacogenetic Model for Optimization of Efavirenz Therapy in Caucasian HIV-Infected Patients

2011 ◽  
Vol 55 (11) ◽  
pp. 5314-5324 ◽  
Author(s):  
Almudena Sánchez ◽  
Salvador Cabrera ◽  
Dolores Santos ◽  
M. Paz Valverde ◽  
Aurelio Fuertes ◽  
...  
Keyword(s):  
High Performance ◽  
Plasma Concentrations ◽  
Compartment Model ◽  
Population Pharmacokinetic ◽  
Nucleotide Polymorphisms ◽  
Mixed Effect ◽  
Factors Affecting ◽  
Nonlinear Mixed Effect ◽  
Study Population ◽  
Major Factors

ABSTRACTDespite extensive clinical experience with efavirenz (EFV), unpredictable interindividual variabilities in efficacy and toxicity remain important limitations associated with the use of this antiretroviral. The purpose of this study was to determine the factors affecting EFV pharmacokinetics and to develop a pharmacokinetic/pharmacogenetic (PK/PG) model in a Caucasian population of HIV-infected patients. In total, 869 EFV plasma concentrations from 128 HIV-infected patients treated with EFV were quantitatively assessed using a validated high-performance liquid chromatography technique. All patients were genotyped for 90 single nucleotide polymorphisms (SNPs) in genes coding for proteins involved in the metabolism and transport of EFV, using a MassArray platform provided by Sequenom. The influence of these polymorphisms on EFV pharmacokinetics and the effects of demographic, clinical, biochemical, lifestyle, and concurrent drug covariates were evaluated. Plasma concentrations were fitted by a one-compartment model, with first-order absorption and elimination using nonlinear mixed-effect modeling (NONMEM program). The CYP2B6*6 allele, multidrug resistance-associated protein 4 (MRP4) 1497C→T, and gamma-glutamyltranspeptidase (GGT) were identified as major factors influencing the apparent EFV oral clearance (CL/F), reducing the initial interindividual variability by 54.8%, according to the model CL/F = (12.2 − 0.00279·GGT)·0.602CYP2B6*6 [G/T]·0.354CYP2B6*6 [T/T]·0.793MRP4 1497C→T, where CYP2B6*6 [G/T], CYP2B6*6 [T/T], and MRP4 1497C→T take values of 0 or 1 to indicate the absence or presence of polymorphisms. The detailed genetic analysis conducted in this study identified two of 90 SNPs that significantly impacted CL/F, which might indicate that the remaining SNPs analyzed do not influence this PK parameter, at least in Caucasian populations with characteristics similar to those of our study population.

Neonatal Kawasaki syndrome presenting as out of hospital cardiac arrest rescued by extracorporeal cardiopulmonary resuscitation

Perfusion ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 86-88
Author(s):  
Marguerite Tyson ◽  
Ala Mustafa ◽  
Prem Venugopal ◽  
Ben Whitehead ◽  
Ben Anderson ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Kawasaki Disease ◽  
Cardiopulmonary Resuscitation ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Pediatric Intensive Care ◽  
Kawasaki Syndrome ◽  
Extracorporeal Cardiopulmonary Resuscitation ◽  
Diagnostic Uncertainty ◽  
Local Emergency Department

A 7-week-old girl presented in severe shock to a local emergency department. During transfer to the quaternary pediatric hospital, the child had a cardiac arrest and cardiopulmonary resuscitation was commenced en route. Upon arrival to the pediatric intensive care unit, extracorporeal life support was initiated via trans-sternal cannulation. Chest CT performed after extracorporeal life support cannulation, demonstrated widespread aneurysms and a diagnosis of Kawasaki disease was made. Immunomodulatory therapy with immunoglobulin and glucocorticoid medication was commenced and the child was separated from extracorporeal life support after 48 hours. Our case highlights both an unusual presentation of Kawasaki disease and the role extracorporeal cardiopulmonary resuscitation can play in the treatment of this disease. It describes the youngest reported patient in the literature with Kawasaki disease rescued by extracorporeal cardiopulmonary resuscitation and highlights how extracorporeal life support therapy can facilitate appropriate investigations to resolve diagnostic uncertainty and treat the underlying condition.

scholarly journals Fuzzy Evaluation of Pharmacokinetic Models

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Carlos Sepúlveda ◽  
Oscar Montiel ◽  
José M. Cornejo Bravo ◽  
Roberto Sepúlveda
Keyword(s):  
Human Error ◽  
Evaluation Criteria ◽  
Multiple Criteria Decision Making ◽  
Population Pharmacokinetic ◽  
Fuzzy Evaluation ◽  
Mixed Effect ◽  
Population Pharmacokinetic Study ◽  
Nonlinear Mixed Effect Model ◽  
Poppk Model ◽  
Selection Of

Population pharmacokinetic (PopPK) models allow researchers to predict and analyze drug behavior in a population of individuals and to quantify the different sources of variability among these individuals. In the development of PopPK models, the most frequently used method is the nonlinear mixed effect model (NLME). However, once the PopPK model has been developed, it is necessary to determine if the selected model is the best one of the developed models during the population pharmacokinetic study, and this sometimes becomes a multiple criteria decision making (MCDM) problem, and frequently, researchers use statistical evaluation criteria to choose the final PopPK model. The used evaluation criteria mentioned above entail big problems since the selection of the best model becomes susceptible to the human error mainly by misinterpretation of the results. To solve the previous problems, we introduce the development of a software robot that can automate the task of selecting the best PopPK model considering the knowledge of human expertise. The software robot is a fuzzy expert system that provides a method to systematically perform evaluations on a set of candidate PopPK models of commonly used statistical criteria. The presented results strengthen our hypothesis that the software robot can be successfully used to evaluate PopPK models ensuring the selection of the best PopPK model.

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

1998 ◽  
Vol 42 (2) ◽  
pp. 289-292 ◽  
Author(s):  
B. Nouaille-Degorce ◽  
C. Veau ◽  
S. Dautrey ◽  
M. Tod ◽  
D. Laouari ◽  
...  
Keyword(s):  
Renal Failure ◽  
Intestinal Secretion ◽  
Parenteral Administration ◽  
Compensatory Mechanisms ◽  
Time Curve ◽  
Mixed Effect ◽  
Nonlinear Mixed Effect Model ◽  
Nonlinear Mixed Effect ◽  
Effect Model ◽  
Elimination Half

ABSTRACT Ciprofloxacin pharmacokinetics have been shown to be modified in patients with renal failure (e.g., the intestinal secretion of ciprofloxacin is increased). This study investigated the influence of renal failure on the pharmacokinetics of ciprofloxacin following oral and parenteral administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CLR) was reduced in nephrectomized rats (5.3 ± 1.4 versus 17.8 ± 4.7 ml/min/kg, P< 0.01, nephrectomized versus control rats). However, nonrenal clearance was increased in nephrectomized rats (32 ± 4 versus 15 ± 5 ml/min/kg, P < 0.01, nephrectomized versus control rats), suggesting compensatory mechanisms for reduced renal function. After oral administration, apparent total clearance and CLR were reduced (P < 0.01) in nephrectomized rats (117 ± 25 and 6.8 ± 4.4 ml/min/kg, respectively) compared with the values for control rats (185 ± 9 and 22.6 ± 5.3 ml/min/kg, respectively) and the area under the concentration-time curve was higher (P < 0.01) for nephrectomized rats (436.3 ± 90.5 mg · min/liter) than for control rats (271.3 ± 14.3 mg · min/liter). Terminal elimination half lives in the two groups remained constant after oral and parenteral administration. These results suggest an increased bioavailability of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.

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