METHODS: Questionnaire study conducted in May-December 2012 on 847 physicians from 255 ICUs in 10 low-middle-income countries and regions according to the World Bank's classification, and 618 physicians from 211 ICUs in six high-income countries and regions.
RESULTS: After we accounted for personal, ICU, and hospital characteristics on multivariable analyses using generalised linear mixed models, physicians from low-middle-income countries and regions were less likely to limit cardiopulmonary resuscitation, mechanical ventilation, vasopressors and inotropes, tracheostomy and haemodialysis than those from high-income countries and regions. They were more likely to involve families in end-of-life care discussions and to perceive legal risks with limitation of life-sustaining treatments and do-not-resuscitate orders. Nonetheless, they were also more likely to accede to families' requests to withdraw life-sustaining treatments in a patient with an otherwise reasonable chance of survival on financial grounds in a case scenario (adjusted odds ratio 5.05, 95 % confidence interval 2.69-9.51, P
METHODS: Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation.
RESULTS: HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2.
CONCLUSION: In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.
METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days.
RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group.
CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).
DESIGN: Cross-sectional observational study.
SETTING: Twenty-three Asian countries and regions, covering 92.1% of the continent's population.
PARTICIPANTS: Ten low-income and lower-middle-income economies, five upper-middle-income economies, and eight high-income economies according to the World Bank classification.
INTERVENTIONS: Data closest to 2017 on critical care beds, including ICU and intermediate care unit beds, were obtained through multiple means, including government sources, national critical care societies, colleges, or registries, personal contacts, and extrapolation of data.
MEASUREMENTS AND MAIN RESULTS: Cumulatively, there were 3.6 critical care beds per 100,000 population. The median number of critical care beds per 100,000 population per country and region was significantly lower in low- and lower-middle-income economies (2.3; interquartile range, 1.4-2.7) than in upper-middle-income economies (4.6; interquartile range, 3.5-15.9) and high-income economies (12.3; interquartile range, 8.1-20.8) (p = 0.001), with a large variation even across countries and regions of the same World Bank income classification. This number was independently predicted by the World Bank income classification on multivariable analysis, and significantly correlated with the number of acute hospital beds per 100,000 population (r = 0.19; p = 0.047), the universal health coverage service coverage index (r = 0.35; p = 0.003), and the Human Development Index (r = 0.40; p = 0.001) on univariable analysis.
CONCLUSIONS: Critical care bed capacity varies widely across Asia and is significantly lower in low- and lower-middle-income than in upper-middle-income and high-income countries and regions.
MAIN BODY: Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty.
CONCLUSIONS: Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.
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.
RESULTS AND CONCLUSIONS: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias.
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.
TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).
METHODS: This observational study collected data closest to 2022 on critical care beds (intensive care units and intermediate care units) in 12 middle-income and 7 high-income economies (using the 2022-2023 World Bank classification), through a mix of methods including government sources, national critical care societies, personal contacts, and data extrapolation. Data were compared with a prior study from 2017 of the same countries and regions.
FINDINGS: The cumulative number of critical care beds per 100,000 population increased from 3.0 in 2017 to 9.4 in 2022 (p = 0.003). The median figure for middle-income economies increased from 2.6 (interquartile range [IQR] 1.7-7.8) to 6.6 (IQR 2.2-13.3), and that for high-income economies increased from 11.4 (IQR 7.3-22.8) to 13.9 (IQR 10.7-21.7). Only 3 countries did not see a rise in bed capacity. Where data were available in 2022, 10.9% of critical care beds were in single rooms (median 5.0% in middle-income and 20.3% in high-income economies), and 5.3% had negative pressure (median 0.7% in middle-income and 18.5% in high-income economies).
INTERPRETATION: Critical care bed capacity in the studied Asian countries and regions increased close to three-fold from 2017 to 2022. Much of this increase was attributed to middle-income economies, but substantial heterogeneity exists.
FUNDING: None.
MATERIALS AND METHODS: In this multicenter cross-sectional study, data on mechanical ventilation and clinical outcomes were collected. Predictors of mortality were analyzed by univariate and multivariable logistic regression. A scoring system was generated to predict 28-day mortality.
RESULTS: A total of 1408 patients were enrolled. In 138 patients with acute respiratory distress syndrome (ARDS), 65.9% were on a tidal volume ≤ 8 ml/kg predicted body weight (PBW), and 71.3% were on sufficient PEEP. In 1270 patients without ARDS, 88.8% were on a tidal volume ≤ 10 ml/kg PBW. A plateau pressure
METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study.
RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p
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.
TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).
METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data.
CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.