Target attainment of cefotaxime in critically ill children with meningococcal septic shock as a model for cefotaxime dosing in severe pediatric sepsis

Importance: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy.Objective: To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis.Design: A retrospective cohort study from previously collected data.Setting: Individual patient data were gathered from three different international datasets.Participants: Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy.Exposure: None.Main Outcome(s) and Measure(s): The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done.Results: We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, p < 0.01], but no differences in sex (41 vs. 43% female, p = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% (p < 0.001), vasoactive drug use 79 vs. 66% (p = 0.13), and mortality 4.6 vs. 34.1% (p < 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in sepsis (p < 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52/66 (78.8%) patients had shock in MIS-C group, and 29/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock.Conclusions and Relevance: IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don't discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases.

Download Full-text

O-10 An observational study on plasma protein binding and target attainment of teicoplanin in critically ill children

Archives of Disease in Childhood ◽

10.1136/archdischild-2017-esdppp.10 ◽

2017 ◽

Vol 102 (10) ◽

pp. A5.1-A5

Author(s):

De Cock ◽

Wollaert ◽

Desmet ◽

McWhinney ◽

De Jaeger ◽

...

Keyword(s):

Observational Study ◽

Protein Binding ◽

Critically Ill ◽

Plasma Protein Binding ◽

Plasma Protein ◽

Critically Ill Children ◽

Target Attainment ◽

O 10

Download Full-text

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

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.80 ◽

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

Download Full-text

P43 Pharmacokinetics and target attainment of antibiotics in critically ill children – a systematic review of current literature

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.81 ◽

2019 ◽

Vol 104 (6) ◽

pp. e35.1-e35

Author(s):

S Hartman ◽

R Brüggemann ◽

L Orriëns ◽

N Dia ◽

M Schreuder ◽

...

Keyword(s):

Critically Ill ◽

Patient Population ◽

Current Knowledge ◽

Volume Of Distribution ◽

Critically Ill Children ◽

Therapeutic Drug ◽

Healthy Children ◽

Target Attainment ◽

Critically Ill Adults ◽

Ill Adults

BackgroundPharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). To what extent this affects the PK of antibiotics in critically children is largely unknown. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.MethodsSystematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, trough concentrations, AUC, probability of target attainment, and elimination half-life.Results45 relevant articles were identified. Studies focusing on vancomycin were most prevalent (15/45). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a larger Vd and higher Cl than healthy children and critically ill adults. Reduced target attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 32/45 articles included information on both Vd and Cl, but a dosing advice was given in only 18 articles.ConclusionThe majority of studies focus on agents where therapeutic drug monitoring is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl that is observed in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.Disclosure(s)Nothing to disclose

Download Full-text

Septic shock and vasopressor requirement is associated with lower vitamin D levels in critically ill children

Critical Care ◽

10.1186/cc10390 ◽

2011 ◽

Vol 15 (S3) ◽

Author(s):

K Madden ◽

HA Feldman ◽

E Smith ◽

CM Gordon ◽

S Keisling ◽

...

Keyword(s):

Vitamin D ◽

Septic Shock ◽

Critically Ill ◽

Critically Ill Children ◽

Vitamin D Levels ◽

Lower Vitamin

Download Full-text

The Association Between Vitamin E Deficiency and Critically Ill Children With Sepsis and Septic Shock

Frontiers in Nutrition ◽

10.3389/fnut.2021.648442 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hongxing Dang ◽

Jing Li ◽

Chengjun Liu ◽

Feng Xu

Keyword(s):

Septic Shock ◽

Vitamin E ◽

Critically Ill ◽

Serum Vitamin ◽

Independent Effect ◽

Critically Ill Children ◽

Vitamin E Deficiency ◽

Suspected Infection ◽

Sepsis And Septic Shock ◽

Vitamin E Status

Background: Literature is scarce on the assessment of vitamin E status in septic children. We aim to investigate the prevalence of vitamin E deficiency in critically ill children with sepsis and septic shock and its association with clinical features and outcomes.Methods: We compared serum vitamin E status between the confirmed or suspected infection and no infection groups, the sepsis shock and no sepsis shock groups upon pediatric intensive care unit admission. Clinical characteristics were compared in subgroup patients with and without vitamin E deficiency. The association between vitamin E deficiency and septic shock were evaluated using univariate and multivariable methods.Results: 182 critically ill children with confirmed or suspected infection and 114 without infection were enrolled. The incidence of vitamin E deficiency was 30.2% in the infection group and 61.9% in the septic shock subgroup (P < 0.001). Thirty-days mortality in critically ill children with vitamin E deficiency was significantly higher than that without vitamin E deficiency (27.3 vs. 14.2%, P < 0.05). Vitamin E levels were inversely associated with higher pediatric risk of mortality (r = − 0.238, P = 0.001) and cardiovascular sequential organ failure assessment (r = −0.249, p < 0.001) scores in critically ill children with infection. In multivariable logistic regression, vitamin E deficiency showed an independent effect on septic shock (adjusted OR: 6.749, 95%CI: 2.449–18.60, P < 0.001).Conclusion: Vitamin E deficiency is highly prevalent in critically ill children with sepsis and contributed to the septic shock.

Download Full-text