Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. 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 Fio2 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/Fio2 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.

Evaluating the outcome of a bundle with 11 components and the INICC multidimensional approach in decreasing rates of central line-associated bloodstream infections across nine Asian countries.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) rates in intensive care units (ICUs) across Latin America exceed those in high-income countries significantly. METHODS: We implemented the INICC multidimensional approach, incorporating an 11-component bundle, in 122 ICUs spanning nine Asian countries. We computed the CLABSI rate using the CDC/NSHN definition and criteria. The CLABSI rate per 1000 CL-days was calculated at baseline and throughout different phases of the intervention, including the 2nd month, 3rd month, 4-16 month, and 17-29 month periods. A two-sample t-test was employed to compare baseline CLABSI rates with intervention rates. Additionally, we utilized a generalized linear mixed model with a Poisson distribution to analyze the association between exposure and outcome. RESULTS: A total of 124,946 patients were hospitalized over 717,270 patient-days, with 238,595 central line (CL)-days recorded. The rates of CLABSI per 1000 CL-days significantly decreased from 16.64 during the baseline period to 6.51 in the 2nd month (RR = 0.39; 95% CI = 0.36-0.42; p < 0.001), 3.71 in the 3rd month (RR = 0.22; 95% CI = 0.21-0.25; p < 0.001), 2.80 in the 4-16 month (RR = 0.17; 95% CI = 0.15-0.19; p < 0.001), and 2.18 in the 17-29 month (RR = 0.13; 95% CI = 0.11-0.15; p < 0.001) intervals. A multilevel Poisson regression model demonstrated a sustained, continuous, and statistically significant decrease in ratios of incidence rates, reaching 0.35 (p < 0.0001) during the 17-29 month period. Moreover, the all-cause in-ICU mortality rate significantly decreased from 13.23% to 10.96% (p = 0.0001) during the 17-29 month period. CONCLUSIONS: Our intervention led to an 87% reduction in CLABSI rates, with a 29-month follow-up.

An international prospective study of INICC analyzing the incidence and risk factors for catheter-associated urinary tract infections in 235 ICUs across 8 Asian Countries.

BACKGROUND: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in 235 ICUs in 8 Asian countries: India, Malaysia, Mongolia, Nepal, Pakistan, the Philippines, Thailand, and Vietnam. METHODS: From January 1, 2014, to February 12, 2022, we conducted a prospective cohort study. To estimate CAUTI incidence, the number of UC days was the denominator, and CAUTI was the numerator. To estimate CAUTI RFs, we analyzed 11 variables using multiple logistic regression. RESULTS: 84,920 patients hospitalized for 499,272 patient days acquired 869 CAUTIs. The pooled CAUTI rate per 1,000 UC-days was 3.08; for those using suprapubic-catheters (4.11); indwelling-catheters (2.65); trauma-ICU (10.55), neurologic-ICU (7.17), neurosurgical-ICU (5.28); in lower-middle-income countries (3.05); in upper-middle-income countries (1.71); at public-hospitals (5.98), at private-hospitals (3.09), at teaching-hospitals (2.04). The following variables were identified as CAUTI RFs: Age (adjusted odds ratio [aOR] = 1.01; 95% CI = 1.01-1.02; P < .0001); female sex (aOR = 1.39; 95% CI = 1.21-1.59; P < .0001); using suprapubic-catheter (aOR = 4.72; 95% CI = 1.69-13.21; P < .0001); length of stay before CAUTI acquisition (aOR = 1.04; 95% CI = 1.04-1.05; P < .0001); UC and device utilization-ratio (aOR = 1.07; 95% CI = 1.01-1.13; P = .02); hospitalized at trauma-ICU (aOR = 14.12; 95% CI = 4.68-42.67; P < .0001), neurologic-ICU (aOR = 14.13; 95% CI = 6.63-30.11; P < .0001), neurosurgical-ICU (aOR = 13.79; 95% CI = 6.88-27.64; P < .0001); public-facilities (aOR = 3.23; 95% CI = 2.34-4.46; P < .0001). DISCUSSION: CAUTI rate and risk are higher for older patients, women, hospitalized at trauma-ICU, neurologic-ICU, neurosurgical-ICU, and public facilities. All of them are unlikely to change. CONCLUSIONS: It is suggested to focus on reducing the length of stay and the Urinary catheter device utilization ratio, avoiding suprapubic catheters, and implementing evidence-based CAUTI prevention recommendations.

Multinational prospective cohort study of incidence and risk factors for central line-associated bloodstream infections over 18 years in 281 ICUs of 9 Asian countries.

BACKGROUND: Our objective was to identify central line (CL)-associated bloodstream infections (CLABSI) rates and risk factors (RF) in Asia. METHODS: From 03/27/2004 to 02/11/2022, we conducted a multinational multicenter prospective cohort study in 281 ICUs of 95 hospitals in 44 cities in 9 Asian countries (China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, and Vietnam). For estimation of CLABSI rate we used CL-days as denominator and number of CLABSI as numerator. To estimate CLABSI RF for we analyzed the data using multiple logistic regression, and outcomes are shown as adjusted odds ratios (aOR). RESULTS: A total of 150,142 patients, hospitalized 853,604 days, acquired 1514 CLABSIs. Pooled CLABSI rate per 1000 CL-days was 5.08; per type of catheter were: femoral: 6.23; temporary hemodialysis: 4.08; jugular: 4.01; arterial: 3.14; PICC: 2.47; subclavian: 2.02. The highest rates were femoral, temporary for hemodialysis, and jugular, and the lowest PICC and subclavian. We analyzed following variables: Gender, age, length of stay (LOS) before CLABSI acquisition, CL-days before CLABSI acquisition, CL-device utilization ratio, CL-type, tracheostomy use, hospitalization type, ICU type, facility ownership and World Bank classifications by income level. Following were independently associated with CLABSI: LOS before CLABSI acquisition, rising risk 4% daily (aOR = 1.04; 95% CI = 1.03-1.04; p < 0.0001); number of CL-days before CLABSI acquisition, rising risk 5% per CL-day (aOR = 1.05; 95% CI 1.05-1.06; p < 0.0001); medical hospitalization (aOR = 1.21; 95% CI 1.04-1.39; p = 0.01); tracheostomy use (aOR = 2.02;95% CI 1.43-2.86; p < 0.0001); publicly-owned facility (aOR = 3.63; 95% CI 2.54-5.18; p < 0.0001); lower-middle-income country (aOR = 1.87; 95% CI 1.41-2.47; p < 0.0001). ICU with highest risk was pediatric (aOR = 2.86; 95% CI 1.71-4.82; p < 0.0001), followed by medical-surgical (aOR = 2.46; 95% CI 1.62-3.75; p < 0.0001). CL with the highest risk were internal-jugular (aOR = 3.32; 95% CI 2.84-3.88; p < 0.0001), and femoral (aOR = 3.13; 95% CI 2.48-3.95; p < 0.0001), and subclavian (aOR = 1.78; 95% CI 1.47-2.15; p < 0.0001) showed the lowest risk. CONCLUSIONS: The following CLABSI RFs are unlikely to change: country income level, facility-ownership, hospitalization type, and ICU type. Based on these findings it is suggested to focus on reducing LOS, CL-days, and tracheostomy; using subclavian or PICC instead of internal-jugular or femoral; and implementing evidence-based CLABSI prevention recommendations.

Multinational prospective cohort study over 18 years of the risk factors for ventilator-associated pneumonia in 9 Asian countries: INICC findings.

BACKGROUND: Ventilator associated pneumonia (VAP) rates in Asia are several times above those of US. The objective of this study is to identify VAP risk factors. METHODS: We conducted a prospective cohort study, between March 27, 2004 and November 2, 2022, in 279 ICUs of 95 hospitals in 44 cities in 9 Asian countries (China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, Vietnam). RESULTS: 153,717 patients, followed during 892,996 patient-days, acquired 3,369 VAPs. We analyzed 10 independent variables. Using multiple logistic regression we identified following independent VAP RFs= Age, rising VAP risk 1% per year (aOR=1.01; 95%CI=1.00-1.01, P<.0001); male gender (OR=1.17; 95%CI=1.08-1.26, P<.0001); length of stay, rising VAP risk 7% daily (aOR=1.07; 95%CI=1.06-1.07, P<.0001); mechanical ventilation (MV) device utilization (DU) ratio (OR=1.43; 95%CI=1.36-1.51; p<.0001); tracheostomy connected to a MV (OR=11.17; 95%CI=9.55-14.27; p<.0001); public (OR=1.84; 95%CI=1.49-2.26, P<.0001), and private (OR=1.57; 95%CI=1.29-1.91, P<.0001) compared with teaching hospitals; upper-middle income country (OR=1.86; 95%CI=1.63-2.14, P<.0001). Regarding ICUs, Medical-Surgical (OR=4.61; 95%CI=3.43-6.17; P<.0001), Neurologic (OR=3.76; 95%CI=2.43-5.82; P<.0001), Medical (OR=2.78; 95%CI=2.04-3.79; P<.0001), and Neuro-Surgical (OR=2.33; 95%CI=1.61-3.92; P<.0001) showed the highest risk. CONCLUSIONS: Some identified VAP RFs are unlikely to change= age, gender, ICU type, facility ownership, country income level. Based on our results, we recommend limit use of tracheostomy, reducing LOS, reducing the MV/DU ratio, and implementing an evidence-based set of VAP prevention recommendations.

Risk factors for mortality over 18 years in 317 ICUs in 9 Asian countries: The impact of healthcare-associated infections.

OBJECTIVE: To identify risk factors for mortality in intensive care units (ICUs) in Asia. DESIGN: Prospective cohort study. SETTING: The study included 317 ICUs of 96 hospitals in 44 cities in 9 countries of Asia: China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, and Vietnam. PARTICIPANTS: Patients aged >18 years admitted to ICUs. RESULTS: In total, 157,667 patients were followed during 957,517 patient days, and 8,157 HAIs occurred. In multiple logistic regression, the following variables were associated with an increased mortality risk: central-line-associated bloodstream infection (CLABSI; aOR, 2.36; P < .0001), ventilator-associated event (VAE; aOR, 1.51; P < .0001), catheter-associated urinary tract infection (CAUTI; aOR, 1.04; P < .0001), and female sex (aOR, 1.06; P < .0001). Older age increased mortality risk by 1% per year (aOR, 1.01; P < .0001). Length of stay (LOS) increased mortality risk by 1% per bed day (aOR, 1.01; P < .0001). Central-line days increased mortality risk by 2% per central-line day (aOR, 1.02; P < .0001). Urinary catheter days increased mortality risk by 4% per urinary catheter day (aOR, 1.04; P < .0001). The highest mortality risks were associated with mechanical ventilation utilization ratio (aOR, 12.48; P < .0001), upper middle-income country (aOR, 1.09; P = .033), surgical hospitalization (aOR, 2.17; P < .0001), pediatric oncology ICU (aOR, 9.90; P < .0001), and adult oncology ICU (aOR, 4.52; P < .0001). Patients at university hospitals had the lowest mortality risk (aOR, 0.61; P < .0001). CONCLUSIONS: Some variables associated with an increased mortality risk are unlikely to change, such as age, sex, national economy, hospitalization type, and ICU type. Some other variables can be modified, such as LOS, central-line use, urinary catheter use, and mechanical ventilation as well as and acquisition of CLABSI, VAE, or CAUTI. To reduce mortality risk, we shall focus on strategies to reduce LOS; strategies to reduce central-line, urinary catheter, and mechanical ventilation use; and HAI prevention recommendations.

Changes Adopted in Asian Pediatric Hospitals during the COVID-19 Pandemic: A Report from the Pediatric Acute and Critical Care COVID-19 Registry of Asia.

There is wide variation in the overall clinical impact of novel coronavirus disease 2019 (COVID-19) across countries worldwide. Changes adopted pertaining to the management of pediatric patients, in particular, the provision of respiratory support during the COVID-19 pandemic is poorly described in Asia. We performed a multicenter survey of 20 Asian pediatric hospitals to determine workflow changes adopted during the pandemic. Data from centers of high-income (HIC), upper middle income (UMIC), and lower middle income (LMIC) countries were compared. All 20 sites over nine countries (HIC: Japan [4] and Singapore [2]; UMIC: China [3], Malaysia [3] and Thailand [2]; and LMIC: India [1], Indonesia [2], Pakistan [1], and Philippines [2]) responded to this survey. This survey demonstrated substantial outbreak adaptability. The major differences between the three income categories were that HICs were (1) more able/willing to minimize use of noninvasive ventilation or high-flow nasal cannula therapy in favor of early intubation, and (2) had greater availability of negative-pressure rooms and powered air-purifying respirators. Further research into the best practices for respiratory support are warranted. In particular, innovation on cost-effective measures in infection control and respiratory support in the LMIC setting should be considered in preparation for future waves of COVID-19 infection.

Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China.

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.

Pediatric Severe Sepsis and Shock in Three Asian Countries: A Retrospective Study of Outcomes in Nine PICUs.

OBJECTIVES: Pediatric sepsis remains a major health problem and is a leading cause of death and long-term disability worldwide. This study aims to characterize epidemiologic, therapeutic, and outcome features of pediatric severe sepsis and septic shock in three Asian countries. DESIGN: A multicenter retrospective study with longitudinal clinical data over 1, 6, 24, 48, and 72 hours of PICU admission. The primary outcome was PICU mortality. Multivariable logistic regression analysis was used to identify factors at PICU admission that were associated with mortality. SETTING: Nine multidisciplinary PICUs in three Asian countries. PATIENTS: Children with severe sepsis or septic shock admitted to the PICU from January to December 2017. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: A total of 271 children were included in this study. Median (interquartile range) age was 4.2 years (1.3-10.8 yr). Pneumonia (77/271 [28.4%]) was the most common source of infection. Majority of patients (243/271 [90%]) were resuscitated within the first hour, with fluid bolus (199/271 [73.4%]) or vasopressors (162/271 [59.8%]). Fluid resuscitation commonly took the form of normal saline (147/199 [74.2%]) (20 mL/kg [10-20 mL/kg] over 20 min [15-30 min]). The most common inotrope used was norepinephrine 81 of 162 (50.0%). Overall PICU mortality was 52 of 271 (19.2%). Improved hemodynamic variables (e.g., heart rate, blood pressure, and arterial lactate) were seen in survivors within 6 hours of admission as compared to nonsurvivors. In the multivariable model, admission severity score was associated with PICU mortality. CONCLUSIONS: Mortality from pediatric severe sepsis and septic shock remains high in Asia. Consistent with current guidelines, most of the children admitted to these PICUs received fluid therapy and inotropic support as recommended.