METHODS: Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h).

RESULTS: Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died.

METHODS: A secondary analysis of a retrospective TBI cohort among participating centers of the Pediatric Acute & Critical Care Medicine Asian Network was performed. Children < 16 years of age with a Glasgow Coma Scale (GCS) score ≤ 13 who were admitted to pediatric intensive care units between January 2014 and October 2017 were included. Logistic regression analysis was performed to study risk factors for EPTS and to investigate the association between EPTS and death, and between EPTS and poor functional outcomes. Poor functional outcomes were defined as moderate disability, severe disability, and coma as defined by the Pediatric Cerebral Performance Category scale.

RESULTS: Overall, 313 children were analyzed, with a median age of 4.3 years (IQR 1.8-8.9 years); 162 children (51.8%) had severe TBI (GCS score < 8), and 76 children (24.3%) had EPTS. After adjusting for age, sex, and the presence of nonaccidental trauma (NAT), only younger age was significantly associated with EPTS (adjusted odds ratio [aOR] 0.85, 95% CI 0.78-0.92; p < 0.001). Forty-nine children (15.6%) in the cohort died, and 87 (32.9%) of the 264 surviving patients had poor functional outcomes. EPTS did not increase the risk of death. After adjusting for age, sex, TBI due to NAT, multiple traumas, and a GCS score < 8, the presence of EPTS was associated with poor functional outcomes (aOR 2.08, 95% CI 1.05-4.10; p = 0.036).

DESIGN: A retrospective study of the Pediatric Acute and Critical Care Medicine Asian Network moderate to severe traumatic brain injury dataset collected between 2014 and 2017.

SETTING: Patients were from the participating PICUs of Pediatric Acute and Critical Care Medicine Asian Network.

PATIENTS: We included children less than 16 years old with a Glasgow Coma Scale less than or equal to 13.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We obtained data on patient demographics, injury circumstances, and PICU management. We performed a multivariate logistic regression predicting for mortality and poor functional outcomes. We analyzed 380 children with moderate to severe traumatic brain injury. Most injuries were a result of road traffic injuries (174 [45.8%]) and falls (160 [42.1%]). There were important differences in temperature control, use of antiepileptic drugs, and hyperosmolar agents between the sites. Fifty-six children died (14.7%), and 104 of 324 survivors (32.1%) had poor functional outcomes. Poor functional outcomes were associated with non-high-income sites (adjusted odds ratio, 1.90; 95% CI, 1.11-3.29), Glasgow Coma Scale less than 8 (adjusted odds ratio, 4.24; 95% CI, 2.44-7.63), involvement in a road traffic collision (adjusted odds ratio, 1.83; 95% CI, 1.04-3.26), and presence of child abuse (adjusted odds ratio, 2.75; 95% CI, 1.01-7.46).

OBJECTIVE: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial.

DESIGN SETTING AND PARTICIPANTS: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial.

MAIN OUTCOME MEASURES: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of patients discharged home.

OBJECTIVE: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial.

DESIGN SETTING AND PARTICIPANTS: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU.

MAIN OUTCOME MEASURES: The primary outcome is in-hospital all-cause mortality up to 90 d from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home.

RESULTS AND CONCLUSIONS: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias.

OBJECTIVE: To summarise the protocol and statistical analysis plan for the Mega-ROX HIE trial.

DESIGN SETTING AND PARTICIPANTS: Mega-ROX HIE is an international randomised clinical trial that will be conducted within an overarching 40,000-participant registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol approximately 4000 participants with suspected HIE following a cardiac arrest who are receiving invasive mechanical ventilation in the ICU.

MAIN OUTCOME MEASURES: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home.

RESULTS AND CONCLUSIONS: Mega-ROX HIE will compare the effect of conservative vs. liberal oxygen therapy regimens on day-90 in-hospital mortality in adults in the ICU with suspected HIE following a cardiac arrest. The protocol and planned analyses are reported here to mitigate analysis bias.