Research

New research ideas

If you have any research ideas that you would like to proposed to the team, please complete the form ↗ (opens in new tab) and email it to Patricia Tay at patricia.tay@scri.cris.sg. Please use this PowerPoint template ↗ (opens in new tab) for your proposal presentation at the annual PACCMAN Meeting.

On-going research

1. Pediatric Acute Respiratory Distress Syndrome Asia Study (PARDSProASIA) -- ClinicalTrials.gov Identifier: NCT04068038

PI: Dr Judith Wong, Department of Children's Intensive Care, KK Women’s and Children’s Hospital

Study Description: Mortality rates in children with pediatric acute respiratory distress syndrome (PARDS) are higher in Asia compared to other regions. In adults with acute respiratory distress syndrome, the only therapy that improves mortality rates is a lung protective ventilation strategy. The pediatric ventilation recommendations are extrapolated from evidence in adults, including ventilation with low tidal volume, low peak/plateau pressures and high-end expiratory pressure. A recent retrospective study of ventilation practices in Asia showed varying practices with regards to pulmonary and non-pulmonary therapies, including ventilation.

Aim: This study aims to determine the prevalence and outcomes of PARDS in the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN). This study will also determine the use of pulmonary (mechanical ventilation, steroids, neuromuscular blockade, surfactant, pulmonary vasodilators, prone positioning) and non-pulmonary (nutrition, sedation, fluid management, transfusion) PARDS therapies.

Study Design: All PICU admission will be screened daily and those who meet the PALICC criteria for PARDS will be recruited and consented (if necessary). We will include those on non-invasive ventilation and alternative modes of ventilation. However, a minimum positive end expiratory pressure of 5cmH2O is necessary for inclusion, as per PALICC. Patients with any type of cardiorespiratory comorbidity will also be included if they fulfill the PALICC criteria for special populations (cyanotic heart disease, chronic lung disease and left ventricular failure). Patients who have limitation of care (i.e. do-not-resuscitate orders) or develop brainstem death will also be included to enable calculation of prevalence.

Study Documents:

For PARDSProAsia I --

PARDSProAsia daily screening workflow ↗ (opens in new tab)

PARDSProAsia screening and enrolment log ↗ (opens in new tab)

PARDSProAsia daily LPMV check ↗ (opens in new tab)

For PARDSProAsia II --

PARDSProAsia II slides ↗ (opens in new tab)

PARDSProAsia II LPMV protocol ↗ (opens in new tab)

PARDSProAsia II database crf4 ↗ (opens in new tab)

PARDSProAsia II PBW_TV chart ↗ (opens in new tab)

PARDSProAsia II Peep FiO2 table ↗ (opens in new tab)

PARDSProAsia II visual reminder ↗ (opens in new tab)

PARDSProAsia II timeline for enrolling centers ↗ (opens in new tab)

2. Does 3% hypertonic saline decrease mortality and improve long-term neurological outcomes among children with traumatic brain injury?

PI: Dr Chong Shu Ling, Department of Emergency Medicine, KK Women’s and Children’s Hospital

Aim: To compare 30-day mortality risk among children < 16 years with moderate to severe TBI treated 3% HTS, compared to mannitol.

Study Design: Prospective Observational Study

Duration: Ongoing

Inclusion and Exclusion criteria: We will include all children < 16 years with moderate to severe TBI (Glasgow Coma Scale [GCS] ≤ 13) who undergo mechanical ventilation in the PICU of participating PACCMAN centres.

Data Collection: Variables defined a priori will be collected on a secure electronic data platform (Redcap) that is designed and maintained by the Singapore Clinical Research Institute (SCRI). Our team research will provide 2-monthly updates on the cases collected and clarify any missing data.

3. Severe Pneumonia in Children (S-PIC) Study: A Comparative Effectiveness Study of Children with Severe Pneumonia in Asia

PI: Dr Lee Jan Hau, Department of Children's Intensive Care, KK Women’s and Children’s Hospital

Abstract: Severe pneumonia is a leading cause of mortality and morbidity in children worldwide. Mortality rates from pediatric severe pneumonia are three times higher in South East Asia compared to the Western hemisphere. The lack of description of epidemiology, current management strategies and outcomes of children with severe pneumonia admitted to pediatric intensive care units (PICUs) in Asia is a barrier to improving paediatric critical care in the region. The lack of a sustainable paediatric critical care network in Asia makes multinational PICU studies challenging.

Aim: To estimate the burden of paediatric patients admitted to Asian PACCMAN PICUs due to severe pneumonia that develop pediatric acute respiratory distress syndrome; To characterize etiologies, identify risk factors associated with morbidity and mortality, and develop prognostic prediction models.

Study Design: A prospective multicenter cohort study over 18 months to recruit 1800 children with severe pneumonia. Pertinent demographic, clinical, microbiological, critical care support and management data will be collected to enable an investigation of the association between risk factors and clinical outcomes in these children.

Completed research

• Risk Stratification in Pediatric Acute Respiratory Distress Syndrome: A Multicenter Observational Study (To access the article, click here ↗ (opens in new tab))

Study description: The Pediatric Acute Lung Injury Consensus Conference (PALICC) developed a pediatric specific definition for acute respiratory distress syndrome (PARDS). In this definition, severity of lung disease is stratified into mild, moderate and severe groups. We aim to describe the epidemiology of patients with PARDS across Asia and evaluate whether the PALICC risk stratification accurately predicts outcome in PARDS. This is a multicenter, retrospective, descriptive cohort study involving 10 multidisciplinary pediatric intensive care units in Asia.

Main findings: A total of 373 patients had mild [89(23.9%)], moderate [149 (39.9%)] and severe PARDS [135 (36.2%)]. 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 113/373 (30.3%), and 100-day mortality was 126/314 (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 (HR) 1.88, 95% confidence interval (CI): 1.03, 3.45; p=0.039] and severe PARDS [HR 3.18 (95% CI 1.68, 6.02); p<0.001] had higher risk of mortality compared to those with mild PARDS.

• Differences Between Pulmonary and Extrapulmonary Pediatric Acute Respiratory Distress Syndrome: A Multicenter Analysis (To access the article, click here ↗ (opens in new tab))

Study description: Pediatric acute respiratory distress syndrome caused by extrapulmonary (PARDSexp) and pulmonary (PARDSp) etiologies is poorly described in the literature. We aimed to describe and compare the epidemiology, risk factors for mortality, and outcomes in PARDSexp and PARDSp. This is a secondary analysis of a multicenter, retrospective, cohort study. Patients were classified into two mutually exclusive groups (PARDSexp and PARDSp) based on etiologies. Primary outcome was pediatric intensive care unit mortality. Cox proportional hazard regression was used to identify risk factors for mortality.

Main findings: Children with PARDSexp had higher admission severity scores, and had a greater proportion of organ dysfunction compared to PARDSp group. Patients in the PARDSexp group had higher mortality (48.8% vs. 24.8%; p = 0.002) and reduced ventilator-free days [median 2.0 (interquartile range 0.0, 18.0) vs. 19.0 (0.5, 24.0) days; p = 0.001] compared to the PARDSp group. However, after adjusting for site, severity of illness, comorbidities, multiorgan dysfunction, and severity of acute respiratory distress syndrome, PARDSexp etiology was not associated with mortality [adjusted hazard ratio 1.56 (95% confidence interval 0.90, 2.71)].

• Early coagulopathy in pediatric traumatic brain injury: A Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) retrospective study (To access the article, click here ↗ (opens in new tab))

Study description: We aim to describe the coagulation profiles in children with moderate to severe TBI, identify predictors of early coagulopathy and investigate the association between early coagulopathy, mortality and functional outcomes in pediatric TBI. Using the Pediatric Acute & Critical Care Medicine Asian Network (PACCMAN) TBI retrospective cohort we identified all patients < 16 years old with a Glasgow Coma Scale (GCS) ≤ 13. We compared prothrombin time (PT), activated partial thromboplastin time (APTT), platelets, and outcomes between children with isolated TBI and those with TBI in the presence of multiple trauma. We performed logistic regression analyses to identify predictors of early coagulopathy and to study the association with mortality and poor functional outcomes.

Main findings: Among 371 children with complete coagulation profiles, the mean age was 5.4 years (SD 4.1). PT was commonly deranged in both isolated TBI (53/173, 30.6%) and multiple trauma (102/198, 51.5%). Independent predictors for early coagulopathy were young age [adjusted odds ratio aOR 0.93, 95% confidence interval (CI) 0.88 – 0.99, p=0.018], low GCS (aOR 0.91, 95%CI 0.86 – 0.97, p=0.002) and presence of multiple trauma (aOR 2.19, 95%CI 1.36 – 3.57, p=0.001). After adjusting for age, gender, GCS, multiple trauma and presence of intracranial bleed, children with early coagulopathy were more likely to die (aOR 7.70, 95%CI 3.09 – 23.53, p<0.001) and have poor neurological outcome (aOR 2.25, 95%CI 1.31 – 3.91, p=0.004). Early coagulopathy is common and independently associated with death and long term poor neurological function among children with TBI. Future trials are required to study the impact of correction of early coagulopathy on clinical outcomes.

• Pediatric Severe Sepsis and Shock in Three Asian Countries: A Retrospective Study of Outcomes in Nine PICUs (To access the article, click here ↗ (opens in new tab))

Study description: 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.

Main findings: 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

• Pediatric Acute and Critical Care COVID-19 Registry of Asia (PACCOVRA)(To access the article, click here ↗ (opens in new tab))

Study description: 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.

Main findings:  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.

• Delphi Study to Establish Paediatric Critical Care Nursing Research Priorities in Asian Countries(To access the article, click here ↗ (opens in new tab))

Study description: Studies showed that nursing care improves patient outcomes, however there are gaps between translation of evidence into clinical practice. Such studies had been done in the USA, Australia and European countries. However, due to cultural, social and economic differences between the Western countries and Asia, the findings from the Western studies may not apply in Asia. Thus a need for the study to be done in an Asia context. This study aims to identify priorities in nursing research as defined by paediatric intensive care nurses across Asia.

Main findings: In round 1, 146 PICU nurses across eight countries provided 520 research topics. Topics from round 1 were categorized into seven domains with 52 research topics. Prioritized research topics included early recognition of patient deterioration (mean 5.58 ± 0.61), prevention of healthcare-associated infections (mean 5.47 ± 0.70), and interventions to reduce compassion fatigue (mean 5.45 ± 0.80). The top three research domains were end-of-life care (mean 5.34 ± 0.68), professionalism (mean 5.34 ± 0.69), and management of pain, sedation, and delirium (5.32 ± 0.72). This first PICU nursing research prioritization exercise within Asia identified key nursing research themes that should be prioritized and provide a framework for future collaborative studies.