Pediatric Critical Care Medicine最新文献

Objectives: Children on extracorporeal membrane oxygenation (ECMO) are at high risk of infection that may worsen prognosis. Even though treatment with beta-lactam antibiotics is frequent, dosing is not adapted to altered pharmacokinetic and pharmacodynamic characteristics of children on ECMO. There is, therefore, a risk of inadequate drug levels when using standard dosing. In this study, we aimed to describe beta-lactam exposures of children on ECMO using current dosing and to identify factors associated with inadequate exposure. The optimal pharmacokinetic/pharmacodynamic target was considered as a plasma concentration four times above the minimum inhibitory concentration throughout the dosing interval target.

Design: Two-center retrospective cohort study.

Setting: Two PICUs in Paris, France.

Patients: Children (from birth to 18 yr) undergoing venovenous or venoarterial ECMO, from 2018 to 2020.

Interventions: None.

Measurements and main results: There were 57 patients who received 11 different beta-lactams, with 226 plasma concentrations analyzed. A total of 32 infections were documented. Overall, 133 of 226 concentrations (58.8%) were insufficient, primarily in samples from children younger than 28 days (p = 0.035), with low body weight (p = 0.013), or in instances of hypoalbuminemia (p = 0.011) and increased renal clearance (p = 0.032). Supratherapeutic concentrations were observed in 25 of 226 samples (11.1%), associated with being taken from patients with renal impairment (p < 0.01).

Conclusions: In this retrospective cohort of pediatric ECMO cases, there is an associated risk of underexposure when prescribing conventional dosing of beta-lactams, which are likely associated with renal impairment and fluid overload. Prospective testing of therapeutic drug monitoring combined with pharmacokinetic/pharmacodynamic models should be tested as a risk-reduction strategy in this vulnerable population.

Objectives: Extubation failure (EF) in PICU patients is reintubation within 48, 72, or 96 hours of planned extubation (EF48, EF72, and EF96, respectively). Standardized sedation protocols, extubation readiness testing, and noninvasive respiratory support are used to improve efficient liberation from mechanical ventilation (MV). We therefore aimed to review EF rates, time to failure, and the use of noninvasive respiratory support after extubation, 2017-2021.

Design: Retrospective analysis of patients admitted to PICUs contributing to the Virtual Pediatric Systems (VPS, LLC) database, 2017-2021.

Setting: One hundred thirty-six participating PICUs.

Patients: All patients admitted to participating PICUs between January 1, 2017, and December 31, 2021, who had MV and met inclusion criteria for planned extubation.

Interventions: None.

Measurements and main results: There were 111,229 planned extubations with 5,143 reintubations within 48 hours. The EF48, EF72, and EF96 rates were 4.6%, 5.3%, and 5.8%, respectively. Higher rates of EF were associated with age younger than 6 months, underlying genetic conditions, medical comorbidities, or cardiac surgery. Failed extubation was also associated with higher Pediatric Risk of Mortality III scores, longer duration of MV, and longer PICU and hospital lengths of stay. From 2017 to 2021, there was an increase in the use of high-flow nasal cannula oxygen therapy after extubation from 16.6% to 20.2%.

Conclusions: In the VPS 2017-2021 dataset, we have found that the overall EF rates (EF48-EF96) have improved over this 5-year period. We are not able to assess the clinical benefit of this change, but it is evident that over the same period, there has been a concomitant increase in the use of postextubation noninvasive respiratory support. Further work is needed to look at the interaction of these effects in contemporary PICU practice.

Objectives: We previously derived the updated Pediatric Sepsis Biomarker Risk for Acute Kidney Injury (PERSEVERE-II AKI) prediction model, which had robust diagnostic test characteristics for severe AKI on day 3 (D3 severe AKI) of septic shock. We now sought to validate this model in an independent cohort of children to the one in which the model was developed.

Design: A secondary analysis of a multicenter, prospective, observational study carried out from January 2019 to December 2022.

Setting: Ten PICUs in the United States.

Patients: Children with septic shock 1 week to 18 years old admitted to the PICU.

Interventions: None.

Measurements and main results: Seventy-nine of 363 patients (22%) had D3 severe AKI, defined as Kidney Disease Improving Global Outcomes stage 2 or higher. Patients were assigned a probability of D3 severe AKI using the PERSEVERE-II AKI model. The model predicted D3 severe AKI with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.85-0.93), sensitivity of 77% (95% CI, 66-86%), specificity of 88% (95% CI, 84-92%), positive predictive value of 65% (95% CI, 54-74%), and negative predictive value of 93% (95% CI, 89-96%). These data represent an increase in post-test probability of D3 severe AKI with a positive test from 22% to 65%, and a prevalence threshold of 28%. On multivariable regression, the PERSEVERE-II AKI prediction model demonstrated greater adjusted odds ratio (aOR) for D3 severe AKI (aOR, 11.2; 95% CI, 4.9-25.3) and lesser aOR for failure of D3 renal recovery from early AKI (aOR, 0.31; 95% CI, 0.13-0.69).

Conclusions: The PERSEVERE-II AKI model demonstrates consistently robust performance for prediction of new or persistent D3 severe AKI in children with septic shock. A major limitation is that actual D3 severe AKI prevalence is below the prevalence threshold for the test, and thus future work should focus on evaluating use in enriched populations.

Objectives: Mortality from pneumonia is three times higher in Asia compared with industrialized countries. We aimed to determine the epidemiology, microbiology, and outcome of severe pneumonia in PICUs across the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN).

Design: Prospective multicenter observational study from June 2020 to September 2022.

Setting: Fifteen PICUs in PACCMAN.

Patients: All children younger than 18 years old diagnosed with pneumonia and admitted to the PICU.

Interventions: None.

Measurements and main results: Clinical, microbiologic, and outcome data were recorded. The primary outcome was PICU mortality. Univariate and multivariable logistic regression was performed to investigate associations between PICU mortality and explanatory risk factors on presentation to the PICU. Among patients screened, 846 of 11,778 PICU patients (7.2%) with a median age of 1.2 years (interquartile range, 0.4-3.7 yr) had pneumonia. Respiratory syncytial virus was detected in 111 of 846 cases (13.1%). The most common bacteria were Staphylococcus species (71/846 [8.4%]) followed by Pseudomonas species (60/846 [7.1%]). Second-generation cephalosporins (322/846 [38.1%]) were the most common broad-spectrum antibiotics prescribed, followed by carbapenems (174/846 [20.6%]). Invasive mechanical ventilation and noninvasive respiratory support was provided in 438 of 846 (51.8%) and 500 of 846 (59.1%) patients, respectively. PICU mortality was 65 of 846 (7.7%). In the multivariable logistic regression model, age (adjusted odds ratio [aOR], 1.08; 95% CI, 1.00-1.16), Pediatric Index of Mortality 3 score (aOR, 1.03; 95% CI, 1.02-1.05), and drowsiness (aOR, 2.73; 95% CI, 1.24-6.00) were associated with greater odds of mortality.

Conclusions: In the PACCMAN contributing PICUs, pneumonia is a frequent cause for admission (7%) and is associated with a greater odds of mortality.

Objectives: Pilot test the nurse-led chronotherapeutic bundle in critically ill children, RESTORE Resilience (R 2 ).

Design: A two-phase cohort study was carried out from 2017 to 2021.

Setting: Two similarly sized and organized PICUs in the United States.

Patients: Children 6 months to 17 years old who were mechanically ventilated for acute respiratory failure.

Interventions: R 2 seven-item chronotherapeutic bundle, including: 1) replication of child's pre-hospital daily routine (i.e., sleep/wake, feeding, activity patterns); 2) cycled day-night light/sound modulation; 3) minimal effective sedation; 4) night fasting with bolus enteral daytime feedings; 5) early progressive mobility; 6) nursing care continuity; and 7) parent diaries.

Measurements and main results: Children underwent environmental (light, sound) and patient (actigraphy, activity log, salivary melatonin, electroencephalogram) monitoring. Parents completed the Child's Daily Routine and Sleep Survey (CDRSS) and Family-Centered Care Scale. The primary outcome was post-extubation daytime activity consolidation (Daytime Activity Ratio Estimate [DARE]). Twenty baseline-phase (2017-2019) and 36 intervention-phase (2019-2021) participants were enrolled. During the intervention phase, nurses used the CDRSS to construct children's PICU schedules. Overall compliance with nurse-implemented R 2 elements 1-5 increased from 18% (interquartile range, 13-30%) at baseline to 63% (53-68%) during the intervention phase ( p < 0.001). Intervention participants were exposed to their pre-hospitalization daily routine ( p = 0.002), cycled day-night light/sound modulation ( p < 0.001), and early progressive mobility on more PICU days ( p = 0.02). Sedation target identification, enteral feeding schedules, and nursing care continuity did not differ between phases. Parent diaries were seldom used. DARE improved during the intervention phase and was higher pre-extubation (median 62% vs. 53%; p = 0.04) but not post-extubation (62% vs. 57%; p = 0.56).

Conclusions: In the PICU, implementation of an individualized nurse-implemented chronotherapeutic bundle is feasible. Children who received the R 2 bundle had increased pre-extubation daytime activity consolidation compared to children receiving usual care. Given variation in protocol adherence, further R 2 testing should include interprofessional collaboration, pragmatic trial design, and implementation science strategies.