The Bacterial Populations of the Gut, Mouth, and Skin are Unstable Over Time in Critically Ill Children

BackgroundProlonged treatment with analgesics and sedatives can result in iatrogenic withdrawal syndrome (IWS) in children being weaned from these drugs.1Personalized weaning strategies might lower the incidence of IWS, but this requires a quantitative understanding of withdrawal over time in individual patients.MethodsData from 81 children (aged 1 month to 17 years) collected during an observational clinical study on IWS2 were used, including a total of 1782 withdrawal assessments performed by PICU nurses, on a numerical rating scale (NRSwithdrawal) from 0 (no withdrawal) to 10 (worst withdrawal possible). Population pharmacokinetic models from literature were used to generate concentration-time profiles in each patient of all key analgesics and sedatives: morphine, fentanyl, methadone, midazolam, lorazepam, propofol, esketamine and clonidine. A mechanism-based withdrawal model was developed using NONMEM 7.3 to quantify IWS over time. The final model was used to perform simulations in which different weaning strategies were compared.ResultsA novel mechanism-based withdrawal model structure was developed with a hypothetical compartment, which equilibrates with the central pharmacokinetic compartment, and which characterizes the development and disappearance of drug dependence over time. With this model and available data, withdrawal dynamics could be established with statistical significance for fentanyl (p< 10-6), morphine (p=0.043) and esketamine (p=0.002), and not for any of the other drugs. Compared with fentanyl, development and disappearance of esketamine and morphine dependence is slower.ConclusionsGiven the patient‘s use of fentanyl, morphine and esketamine, the developed model can dynamically predict IWS from these substances under different weaning strategies. The results show that the optimal strategy for weaning of drug dependent children depends on both the type of drug and the drug levels prior to weaning. In this study, there was insufficient information to characterise midazolam withdrawal dynamics, potentially because of slow midazolam weaning with insufficiently high NRSwithdrawal scores.ReferencesBest KM, Boullata JI, Curley MAQ. Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: A Systematic Review and Conceptual Model. Pediatr Crit Care Med ( 2015) 16(2): 175–183.Ista E, de Hoog M, Tibboel D, Duivenvoorden HJ, van Dijk M. Psychometric evaluation of the sophia observation withdrawal symptoms scale in critically ill children. Pediatr Crit Care Med ( 2013).14(8): 761–769.Disclosure(s)Nothing to disclose

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Association of monocyte HLA-DR expression over time with secondary infection in critically ill children: a prospective observational study

European Journal of Pediatrics ◽

10.1007/s00431-021-04313-7 ◽

2021 ◽

Author(s):

Nienke N. Hagedoorn ◽

Pinar Kolukirik ◽

Nicole M. A. Nagtzaam ◽

Daan Nieboer ◽

Sascha Verbruggen ◽

...

Keyword(s):

Immune Response ◽

Observational Study ◽

Critically Ill ◽

Prospective Observational Study ◽

Secondary Infection ◽

Critically Ill Children ◽

Healthy Controls ◽

Secondary Infections ◽

Impaired Immune Response ◽

Over Time

AbstractAn impaired immune response could play a role in the acquisition of secondary infections in critically ill children. Human leukocyte antigen-DR expression on monocytes (mHLA-DR) has been proposed as marker to detect immunosuppression, but its potential to predict secondary infections in critically ill children is unclear. We aimed to assess the association between mHLA-DR expression at several timepoints and the change of mHLA-DR expression over time with the acquisition of secondary infections in critically ill children. In this prospective observational study, children < 18 years with fever and/or suspected infection (community-acquired or hospital-acquired) were included at a paediatric intensive care unit in the Netherlands. mHLA-DR expression was determined by flow cytometry on day 1, day 2–3 and day 4–7. The association between delta-mHLA-DR expression (difference between last and first measurement) and secondary infection was assessed by multivariable regression analysis, adjusted for age and Paediatric Logistic Organ Dysfunction-2 score. We included 104 patients at the PICU (median age 1.2 years [IQR 0.3–4.2]), of whom 28 patients (27%) developed a secondary infection. Compared to 93 healthy controls, mHLA-DR expression of critically ill children was significantly lower at all timepoints. mHLA-DR expression did not differ at any of the time points between patients with and without secondary infection. In addition, delta-mHLA-DR expression was not associated with secondary infection (aOR 1.00 [95% CI 0.96–1.04]).Conclusions: Our results confirm that infectious critically ill children have significantly lower mHLA-DR expression than controls. mHLA-DR expression was not associated with the acquisition of secondary infections. What is Known:• An impaired immune response, estimated by mHLA-DR expression, could play an essential role in the acquisition of secondary infections in critically ill children.• In critically ill children, large studies on the association of mHLA-DR expression with secondary infections are scarce. What is New:• Our study confirms that critically ill children have lower mHLA-DR expression than healthy controls.• mHLA-DR expression and change in mHLA-DR was not associated with the acquisition of secondary infection.

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Evolution of inspiratory muscle function in children during mechanical ventilation

Critical Care ◽

10.1186/s13054-021-03647-w ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Benjamin Crulli ◽

Atsushi Kawaguchi ◽

Jean-Paul Praud ◽

Basil J. Petrof ◽

Karen Harrington ◽

...

Keyword(s):

Mechanical Ventilation ◽

Critically Ill ◽

Regression Coefficient ◽

Elective Surgery ◽

Mechanical Efficiency ◽

Inspiratory Muscle ◽

Critically Ill Children ◽

Respiratory Drive ◽

Inspiratory Muscles ◽

Over Time

Abstract Background There is no universally accepted method to assess the pressure-generating capacity of inspiratory muscles in children on mechanical ventilation (MV), and no study describing its evolution over time in this population. Methods In this prospective observational study, we have assessed the function of the inspiratory muscles in children on various modes of MV. During brief airway occlusion maneuvers, we simultaneously recorded airway pressure depression at the endotracheal tube (ΔPaw, force generation) and electrical activity of the diaphragm (EAdi, central respiratory drive) over five consecutive inspiratory efforts. The neuro-mechanical efficiency ratio (NME, ΔPaw/EAdimax) was also computed. The evolution over time of these indices in a group of children in the pediatric intensive care unit (PICU) was primarily described. As a secondary objective, we compared these values to those measured in a group of children in the operating room (OR). Results In the PICU group, although median NMEoccl decreased over time during MV (regression coefficient − 0.016, p = 0.03), maximum ΔPawmax remained unchanged (regression coefficient 0.109, p = 0.50). Median NMEoccl at the first measurement in the PICU group (after 21 h of MV) was significantly lower than at the only measurement in the OR group (1.8 cmH2O/µV, Q1–Q3 1.3–2.4 vs. 3.7 cmH2O/µV, Q1–Q3 3.5–4.2; p = 0.015). Maximum ΔPawmax in the PICU group was, however, not significantly different from the OR group (35.1 cmH2O, Q1–Q3 21–58 vs. 31.3 cmH2O, Q1–Q3 28.5–35.5; p = 0.982). Conclusions The function of inspiratory muscles can be monitored at the bedside of children on MV using brief airway occlusions. Inspiratory muscle efficiency was significantly lower in critically ill children than in children undergoing elective surgery, and it decreased over time during MV in critically ill children. This suggests that both critical illness and MV may have an impact on inspiratory muscle efficiency.

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