scholarly journals Midazolam Infusion and Disease Severity Affect the Level of Sedation in Children: A Parametric Time-to-Event Analysis

2021 ◽  
Author(s):  
Parth J. Upadhyay ◽  
Nienke J. Vet ◽  
Sebastiaan C. Goulooze ◽  
Elke H. J. Krekels ◽  
Saskia N. de Wildt ◽  
...  
Keyword(s):  
Disease Severity ◽  
Critically Ill ◽  
External Validation ◽  
Analysis Data ◽  
Critically Ill Children ◽  
Event Analysis ◽  
Time To Event ◽  
Mechanically Ventilated ◽  
Midazolam Infusion ◽  
High Disease Severity

Abstract Aim In critically ill mechanically ventilated children, midazolam is used first line for sedation, however its exact sedative effects have been difficult to quantify. In this analysis, we use parametric time-to-event (PTTE) analysis to quantify the effects of midazolam in critically ill children. Methods In the PTTE analysis, data was analyzed from a published study in mechanically ventilated children in which blinded midazolam or placebo infusions were administered during a sedation interruption phase until, based on COMFORT-B and NISS scores, patients became undersedated and unblinded midazolam was restarted. Using NONMEM® v.7.4.3., restart of unblinded midazolam was analysed as event. Patients in the trial were divided into internal and external validation cohorts prior to analysis. Results Data contained 138 events from 79 individuals (37 blinded midazolam; 42 blinded placebo). In the PTTE model, the baseline hazard was best described by a constant function. Midazolam reduced the hazard for restart of unblinded midazolam due to undersedation by 51%. In the blinded midazolam group, time to midazolam restart was 26 h versus 58 h in patients with low versus high disease severity upon admission (PRISM II < 10 versus > 21), respectively. For blinded placebo, these times were 14 h and 33 h, respectively. The model performed well in an external validation with 42 individuals. Conclusion The PTTE analysis effectively quantified the effect of midazolam in prolonging sedation and also the influence of disease severity on sedation in mechanically ventilated critically ill children, and provides a valuable tool to quantify the effect of sedatives. Clinical trial number and registry URL: Netherlands Trial Register, Trial NL1913 (NTR2030), date registered 28 September 2009 https://www.trialregister.nl/trial/1913.

scholarly journals Midazolam infusion and disease severity affect the level of sedation in children: a parametric time-to-event analysis of data from the ‘daily sedation interruption in critically ill children’ trial

2021 ◽  
Author(s):  
Parth Upadhyay ◽  
Nienke Vet ◽  
Sebastiaan Goulooze ◽  
Elke Krekels ◽  
Saskia De wildt ◽  
...  
Keyword(s):  
Disease Severity ◽  
Critically Ill ◽  
External Validation ◽  
Analysis Data ◽  
Clinical Event ◽  
Critically Ill Children ◽  
Event Analysis ◽  
Time To Event ◽  
Mechanically Ventilated ◽  
Midazolam Infusion

Aim In critically ill mechanically ventilated children, midazolam is used first line for sedation, however its sedative effects have been difficult to quantify for which novel quantification methods are still required. In this analysis, we use parametric time-to-event (PTTE) analysis to quantify the effects of midazolam in critically ill children. Methods For the PTTE analysis, data was analyzed from a published sedation interruption study in mechanically ventilated critically ill children. In this study, blinded midazolam or placebo infusions were administered during the sedation interruption phase until, based on COMFORT-B and NISS scores, patients became undersedated and unblinded midazolam was restarted. Using NONMEM® v.7.4.3.,the restart of unblinded midazolam was analysed as a clinical event, followed by internal and external validation. Results Data contained 138 events from 79 individuals (37 blinded midazolam; 42 blinded placebo). In the PTTE model, a constant function best described the baseline hazard. The use of midazolam reduced the hazard for restart of unblinded midazolam due to undersedation by 51%. In the blinded midazolam group, time to midazolam restart was 26 h versus 58 h in patients with low versus high disease severity upon admission (PRISM II <10 versus > 21), respectively. For blinded placebo these times were 14 h and 33 h, respectively. The model performed well in an external validation with 42 individuals. Conclusion The PTTE analysis effectively quantified the effect of midazolam and the influence of disease severity on sedation in mechanically ventilated critically ill children and provides a valuable tool to quantify sedative efficacy

scholarly journals P42 External validation of model-based dosing guidelines for vancomycin, gentamicin and tobramycin in critically ill children

2019 ◽  
Vol 104 (6) ◽  
pp. e34.2-e34
Author(s):  
S Hartman ◽  
S Zwaag ◽  
L Orriëns ◽  
T Poel ◽  
M de Hoop - Sommen ◽  
...  
Keyword(s):  
Critically Ill ◽  
Clinical Laboratory ◽  
External Validation ◽  
Interindividual Variation ◽  
Critically Ill Children ◽  
Target Range ◽  
Future Research ◽  
Target Attainment ◽  
Model Based ◽  
Trough Concentrations

BackgroundPharmacokinetic models are frequently used to simulate dosing strategies for special populations, including critically ill children. The Dutch Pediatric Formulary (DPF) partially bases its guidelines on these models. However, prospective validation of updated dosing regimens is rare. We aimed to identify target attainment and safety of vancomycin, gentamicin and tobramycin after a dose update in the DPF for critically ill neonates and children.MethodsRetropsective cohort study in PICU and NICU patients receiving vancomycin, gentamicin or tobramycin between January 2015 and March 2017 in 2 university hospitals. Demographic clinical laboratory and TDM-data were collected. Target (steady state) trough concentrations for vancomycin, gentamicin and tobramycin used were 10–15, ≤1 and ≤1 mg/l, respectively. Target gentamicin peak concentrations used were 8–12 mg/l.Results486 patients were included in total (165 vancomycin, 97 gentamicin and 224 tobramycin). Trough concentrations of vancomycin, gentamicin and tobramycin were within the target range in 37.5%, 85.3% and 77.2% of patients, respectively. Target attainment of gentamicin peak concentrations in NICU patients was 31%. Non-target trough concentrations were most prevalent in term NICU patients (vancomycin 70%, gentamicin 26% and tobramycin 36.8%). Gentamicin peak concentrations were subtherapeutic in 91% and 45.5% for term and preterm NICU patients, respectively. Creatinine concentrations correlated positively with antibiotic concentrations (correlation coefficient range 0.46–0.54, p≤0.01 in all cohorts).ConclusionDespite recent model-based dosing alterations, sub- and supratherapeutic concentrations of vancomycin, gentamicin and tobramycin are still frequent in critically ill children. Linear dose alterations did offer improvements in target attainment, but did not fully address all relevant covariates that contribute to the large interindividual variation in clearance and/or volume of distribution in these patients. Creatinine clearance was consistently correlated with concentrations of all 3 drugs, but future research is needed to identify whether including this parameter in dosing can improve target attainment and safety.Disclosure(s)Nothing to disclose

Evaluation of the New Centers for Disease Control and Prevention Ventilator-Associated Event Module and Criteria in Critically Ill Children in Greece

2016 ◽  
Vol 37 (10) ◽  
pp. 1162-1166 ◽  
Author(s):  
Elias Iosifidis ◽  
Elpis Chochliourou ◽  
Asimenia Violaki ◽  
Elisavet Chorafa ◽  
Stavroula Psachna ◽  
...  
Keyword(s):  
Disease Control ◽  
Critically Ill ◽  
Pediatric Intensive Care ◽  
Critically Ill Children ◽  
Ventilator Associated Pneumonia ◽  
Poor Agreement ◽  
Mechanically Ventilated ◽  
Risk Of Mortality ◽  
Control And Prevention ◽  
Centers For Disease Control

OBJECTIVETo evaluate the new adult Centers for Disease Control and Prevention (CDC) ventilator-associated event (VAE) module in critically ill children and compare with the traditionally used CDC definition for ventilator-associated pneumonia (VAP).DESIGNRetrospective observational study of mechanically ventilated children in a pediatric intensive care unit in Greece January 1-December 31, 2011.METHODSAssessment of new adult CDC VAE module including 3 definition tiers: ventilator-associated condition (VAC), infection-related VAC, and possible/probable ventilator-associated pneumonia (VAE-VAP); comparison with traditional CDC criteria for clinically defined pneumonia in mechanically ventilated children (PNEU-VAP). We recorded Pediatric Risk of Mortality score at admission (PRISM III), number of ventilator-days, and outcome.RESULTSAmong 119 patients with mechanical ventilation (median [range] number of ventilator-days, 7 [1–183]), 19 patients experienced VAC. Criteria for VAE-VAP were fulfilled in 12 of 19 patients with VAC (63%). Children with either VAC or VAE-VAP were on ventilation more days than patients without these conditions (16.5 vs 5 d, P=.0006 and 18 vs 5 d, P<.001, respectively), whereas PRISM-III score was similar between them. Mortality was significant higher in patients with new VAE-VAP definition (50%), but not in patients with VAC (31.6%), than the patients without new VAE-VAP (14%, P=.007) or VAC (15%, P=.1), respectively. No significant association was found between PNEU-VAP and death. Incidences of PNEU-VAP and VAE-VAP were similar, but the agreement was poor.CONCLUSIONSVAE-VAP and PNEU-VAP found similar prevalence in critically ill children but with poor agreement. However, excess of death was significantly associated only with VAE-VAP.Infect Control Hosp Epidemiol 2016:1–5

scholarly journals Myocardial Injury in Critically Ill Children: A Case Control Study

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Basheir Hassan ◽  
Saed Morsy ◽  
Ahmed Siam ◽  
Al Shaymaa Ali ◽  
Mohamed Abdo ◽  
...  
Keyword(s):  
Disease Severity ◽  
Critically Ill ◽  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Case Control Study ◽  
Troponin T ◽  
Critically Ill Children ◽  
Cardiac Troponin T ◽  
Healthy Children ◽  
Control Study

Objectives. The aim of this study was to investigate the occurrence of myocardial injury in critically ill children through assessment of cardiac troponin T levels and whether levels are associated with disease severity and myocardial dysfunction measured by echocardiography. Methods. Over a 6-month period, this case control study included 50 patients admitted to Pediatric Intensive Care Unit of Zagazig University Children’s Hospital. Twenty-five healthy children were included as a control group. Demographic and clinical data including the pediatric index of mortality II score were recorded. Echocardiographic examination was done and level of cardiac troponin T was measured using Elecsys Troponin T STAT Immunoassay. Results. Cardiac troponin T levels were significantly higher in critically ill in comparison to healthy children (median 22 (18–28) pg/mL versus 10 (10-10) pg/mL, P<0.05). Cardiac troponin T levels correlated positively with duration of ventilation as well as with disease severity and correlated negatively with left ventricular fractional shortening. Moreover, cardiac troponin T levels were significantly higher in nonsurvivors when compared to survivors (median 34.5 (27.5–41.5) pg/mL versus 20 (18–24) pg/mL, P<0.05). Conclusion. In critically ill children, cardiac troponin T levels were elevated and were associated with duration of ventilation and disease severity.

scholarly journals A study on symptoms of children mechanically ventilated in a paediatric intensive care unit of a minimum resource setting in tertiary care centre

2019 ◽  
Vol 6 (2) ◽  
pp. 574
Author(s):  
Korisipati Ankireddy ◽  
Aruna Jyothi K.
Keyword(s):  
Intensive Care Unit ◽  
Mechanical Ventilation ◽  
Intensive Care ◽  
Critically Ill ◽  
Tertiary Care ◽  
Limited Resource ◽  
Critically Ill Children ◽  
Invasive Ventilation ◽  
Ventilator Support ◽  
Mechanically Ventilated

Background: Mechanical ventilation, a lifesaving intervention in a critical care unit is under continuous evolution in modern era. Despite this, the management of children with invasive ventilation in developing countries with limited resources is challenging. The study analyses the clinical profile, indications, complications and duration of ventilator care in limited resource settings. Methods: A retrospective study of critically ill children mechanically ventilated in an intensive care unit of a tertiary care government hospital.   Results: A total of 120 children required invasive ventilation during the study period of 1 year. Infants constituted the majority (70%), and males (65%) were marginally more than female children (35%). Respiratory failure was the most common indication for invasive ventilation (55%). The major underlying etiology for invasive ventilation was bronchopneumonia associated with septic shock (30%); and the same also required a prolonged duration of ventilation of >72 hours (35%). Prolonged ventilator support of >72 hours predisposed to more complications as well as a prolonged hospital stay of >2 weeks and above, which was statistically significant. Upper lobe atelectasis (50%) and ventilator associated pneumonia (25%) were the major complications. The mortality rate of present study population was 40% as opposed to the overall mortality of 10%.   Conclusions: Present study highlights that critically ill children can be managed with mechanical ventilation even in limited resource settings. The child should be assessed clinically regarding the tolerance to extubation every day, to minimise the complications associated with prolonged ventilator support.

scholarly journals Nutritional Status Based on Body Mass Index Is Associated With Morbidity and Mortality in Mechanically Ventilated Critically Ill Children in the PICU*

2016 ◽  
Vol 44 (8) ◽  
pp. 1530-1537 ◽  
Author(s):  
Lori J. Bechard ◽  
Christopher Duggan ◽  
Riva Touger-Decker ◽  
J. Scott Parrott ◽  
Pamela Rothpletz-Puglia ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Nutritional Status ◽  
Critically Ill ◽  
Body Mass ◽  
Morbidity And Mortality ◽  
Critically Ill Children ◽  
Mechanically Ventilated

scholarly journals Red cell distribution width as a prognostic marker in mechanically ventilated children admitted in pediatric critical care unit of tertiary care centre, India

2018 ◽  
Vol 5 (5) ◽  
pp. 1794
Author(s):  
Swati M. Gadappa ◽  
Manas Kumar Behera
Keyword(s):  
Mechanical Ventilation ◽  
Length Of Stay ◽  
Critically Ill ◽  
Red Cell Distribution Width ◽  
Critically Ill Children ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width ◽  
Mechanically Ventilated ◽  
Prospective Longitudinal

Background: Paediatric population is a vulnerable group necessitating standard care for medically and surgically ill children. Red cell distribution width (RDW) is a simple and low-cost measure that denotes the variability in red blood cell size. Any process that releases reticulocytes in the circulation will result in an increase in RDW. RDW may also be useful as a biomarker of disease severity and clinical outcomes in critically ill patients. Methods: Retrospective cohort study of all patients between 1month-12yrs of age, mechanically ventilated in Paediatric intensive care unit. Those patients with RDW on admission and complete data for PIM3 (Paediatric Index of Mortality 3) were included. Analyses included correlation, logistic regression analysis, and receiver operating characteristic (ROC) curves.Results: Retrospective analysis of data on 93 consecutive critically ill children admitted in PICU was done between Jan 2015- June 2016. We noted statistically significant correlation between mortality and anemia (10.24 g/dL, SD 2.26; 8.78 g/dL, SD 2.60.p = 0.009), LOS on MV (p = 0.008), RDW (p = 0.002), shock (p = 0.004) and ventilator associated Pneumonia (p = 0.024).  Mortality increased as length of stay on mechanical ventilation increased (4.13 days, SD 2.125 versus 6.94 days, SD 7.603 p = 0.008). The cut-off of 18.10 was chosen as Mean RDW. Based on AUROC, RDW is independently associated with high risk of mortality.Conclusions: RDW measured within 24 hours of PICU admission was independently associated with length of stay on mechanical ventilation and mortality in a general PICU population. We recommend the need for multicentric, prospective longitudinal studies to determine the optimum utility of RDW to enhance decision making in PICU.

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