METHODS: There were 5 patients, with a median age of 1.75 (range 0.1-6.25) years, a median weight of 10.7 (2.9-21.5) kg, and a median creatinine clearance of 179 (44-384) mL/min/1.73m2, who received intravenous infusions of colistimethate each 8 hours. The median daily dose was 0.21 (0.20-0.21) million international units/kg, equivalent to 6.8 (6.5-6.9) mg of colistin base activity per kg/day. Plasma concentrations of colistimethate and formed colistin were subjected to population pharmacokinetic modeling to explore the patient factors influencing the concentration of colistin.
RESULTS: The median, average, steady-state plasma concentration of colistin (Css,avg) was 0.88 mg/L; individual values ranged widely (0.41-3.50 mg/L), even though all patients received the same body weight-based daily dose. Although the daily doses were ~33% above the upper limit of the FDA- and EMA-recommended dose range, only 2 patients achieved Css,avg ≥2mg/L; the remaining 3 patients had Css,avg <1mg/L. The pharmacokinetic covariate analysis revealed that clearances of colistimethate and colistin were related to creatinine clearance.
CONCLUSIONS: The FDA and EMA dosage recommendations may be suboptimal for many pediatric patients. Renal functioning is an important determinant of dosing in these patients.
DATA COLLECTION: A systematic search was performed using the following databases: Medline, EMBASE, CINAHL, and Cochrane from January 1990 till December 2022. Comparative studies of TPE in severe sepsis were selected. Adult and pediatric data were analyzed separately.
DATA SYNTHESIS: Eight randomized control trials and 6 observational studies (n = 50,142 patients) were included. Centrifugal TPE was the most common modality (209/280, 74.6% adults and 952/1026, 92.7% children). Every TPE study utilized different volume exchanges. Most TPE sessions (1173/1306, 89.8%) employed fresh frozen plasma (FFP) as replacement fluid and heparin as anticoagulant. Adults with severe sepsis supported with TPE using FFP had lower mortality (risk ratio, RR: 0.64 [95% confidence interval, CI: 0.49, 0.84]) compared to those who did not. In contrast, TPE was associated with increased mortality in septic children without thrombocytopenia-associated multiorgan failure (RR: 2.23, 95% CI: 1.93, 2.57). There was no difference in outcomes in patients supported with centrifugal and membrane TPE. In both populations, patients supported on TPE as a continuous regime had poorer outcome.
CONCLUSION: Current evidence indicates that TPE is a potential adjunct therapy in adults with severe sepsis but not in children.
CASE PRESENTATION: A 4 years old girl presented with history of recurrent haemoptysis. Bronchoscopic evaluation excluded a foreign body aspiration but revealed right bronchial mucosal hyperaemia and varices. Diagnosis of right unilateral PVA was suspected on transthoracic echocardiography which demonstrated hypoplastic right pulmonary artery and non-visualization of right pulmonary veins. Final diagnosis was confirmed on cardiac CT angiography. A conservative treatment approach was opted with consideration for pneumonectomy in future when she is older.
CONCLUSION: Rarer causes should be considered when investigating for recurrent haemoptysis in children. Bronchoscopy and cardiac imaging are useful tools to establish the diagnosis of unilateral PVA in our case.
DESIGN: A multicenter, retrospective, descriptive cohort study.
SETTING: Ten multidisciplinary PICUs in Asia.
PATIENTS: All mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for PARDS between 2009 and 2015.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Data on epidemiology, ventilation, adjunct therapies, and clinical outcomes were collected. Patients were followed for 100 days post diagnosis of PARDS. A total of 373 patients were included. There were 89 (23.9%), 149 (39.9%), and 135 (36.2%) patients with mild, moderate, and severe PARDS, respectively. The most common risk factor for PARDS was pneumonia/lower respiratory tract infection (309 [82.8%]). Higher category of severity of PARDS was associated with lower ventilator-free days (22 [17-25], 16 [0-23], 6 [0-19]; p < 0.001 for mild, moderate, and severe, respectively) and PICU free days (19 [11-24], 15 [0-22], 5 [0-20]; p < 0.001 for mild, moderate, and severe, respectively). Overall PICU mortality for PARDS was 113 of 373 (30.3%), and 100-day mortality was 126 of 317 (39.7%). After adjusting for site, presence of comorbidities and severity of illness in the multivariate Cox proportional hazard regression model, patients with moderate (hazard ratio, 1.88 [95% CI, 1.03-3.45]; p = 0.039) and severe PARDS (hazard ratio, 3.18 [95% CI, 1.68, 6.02]; p < 0.001) had higher risk of mortality compared with those with mild PARDS.
CONCLUSIONS: Mortality from PARDS is high in Asia. The Pediatric Acute Lung Injury Consensus Conference definition of PARDS is a useful tool for risk stratification.
DESIGN: This is a secondary analysis of a multicenter, retrospective, cohort study. Data on epidemiology, ventilation, therapies, and outcomes were collected and analyzed. Patients were classified into two mutually exclusive groups (extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome) based on etiologies. Primary outcome was PICU mortality. Cox proportional hazard regression was used to identify risk factors for mortality.
SETTING: Ten multidisciplinary PICUs in Asia.
PATIENTS: Mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric acute respiratory distress syndrome between 2009 and 2015.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Forty-one of 307 patients (13.4%) and 266 of 307 patients (86.6%) were classified into extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome groups, respectively. The most common causes for extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome were sepsis (82.9%) and pneumonia (91.7%), respectively. Children with extrapulmonary pediatric acute respiratory distress syndrome were older, had higher admission severity scores, and had a greater proportion of organ dysfunction compared with pulmonary pediatric acute respiratory distress syndrome group. Patients in the extrapulmonary pediatric acute respiratory distress syndrome group had higher mortality (48.8% vs 24.8%; p = 0.002) and reduced ventilator-free days (median 2.0 d [interquartile range 0.0-18.0 d] vs 19.0 d [0.5-24.0 d]; p = 0.001) compared with the pulmonary pediatric acute respiratory distress syndrome group. After adjusting for site, severity of illness, comorbidities, multiple organ dysfunction, and severity of acute respiratory distress syndrome, extrapulmonary pediatric acute respiratory distress syndrome etiology was not associated with mortality (adjusted hazard ratio, 1.56 [95% CI, 0.90-2.71]).
CONCLUSIONS: Patients with extrapulmonary pediatric acute respiratory distress syndrome were sicker and had poorer clinical outcomes. However, after adjusting for confounders, it was not an independent risk factor for mortality.
METHODS: Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect.
RESULTS: A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p
DESIGN: Multicenter prospective before-and-after comparison design study.
SETTING: Twenty-one PICUs.
PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation.
INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to F io2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets.
MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/F io2 combinations were associated with reduced mortality.
CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.
OBJECTIVE: To compare mortality and functional outcomes of treatment with 3% HTS vs 20% mannitol among children with moderate to severe traumatic brain injury (TBI) at risk of elevated ICP.
DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study was conducted between June 1, 2018, and December 31, 2022, at 28 participating pediatric intensive care units in the Pediatric Acute and Critical Care Medicine in Asia Network (PACCMAN) and the Red Colaborativa Pediátrica de Latinoamérica (LARed) in Asia, Latin America, and Europe. The study included children (aged <18 years) with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤13).
EXPOSURE: Treatment with 3% HTS compared with 20% mannitol.
MAIN OUTCOMES AND MEASURES: Multiple log-binomial regression analysis was performed for mortality, and multiple linear regression analysis was performed for discharge Pediatric Cerebral Performance Category (PCPC) scores and 3-month Glasgow Outcome Scale-Extended Pediatric Version (GOS-E-Peds) scores. Inverse probability of treatment weighting was also performed using the propensity score method to control for baseline imbalance between groups.
RESULTS: This study included 445 children with a median age of 5.0 (IQR, 2.0-11.0) years. More than half of the patients (279 [62.7%]) were boys, and 344 (77.3%) had severe TBI. Overall, 184 children (41.3%) received 3% HTS, 82 (18.4%) received 20% mannitol, 69 (15.5%) received both agents, and 110 (24.7%) received neither agent. The mortality rate was 7.1% (13 of 184 patients) in the HTS group and 11.0% (9 of 82 patients) in the mannitol group (P = .34). After adjusting for age, sex, presence of child abuse, time between injury and hospital arrival, lowest GCS score in the first 24 hours, and presence of extradural hemorrhage, no between-group differences in mortality, hospital discharge PCPC scores, or 3-month GOS-E-Peds scores were observed.
CONCLUSIONS AND RELEVANCE: In this cohort study of children with moderate to severe TBI, the use of HTS was not associated with increased survival or improved functional outcomes compared with mannitol. Future large multicenter randomized clinical trials are required to validate these findings.