Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Extubation in neurocritical care patients: the ENIO international prospective study

Purpose: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. Methods: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. Results: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). Conclusions: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort

Evaluating the Sum of Eye and Motor Components of the Glasgow Coma Score As a Predictor of Extubation Failure in Patients With Acute Brain Injury

Objectives: To evaluate the association between the pre-extubation sum of eye and motor components of the Glasgow Coma Score (GCS-EM) and odds of extubation failure in patients with acute brain injury being liberated from mechanical ventilation. Design: Secondary analysis of a prospective, multicenter observational study (ClinicalTrials.gov identifier NCT03400904). Setting: Sixty-three hospital sites worldwide, with patient recruitment from January 2018 to November 2020. Patients: One thousand one hundred fifty-two critically ill patients with acute brain injury, with a median age of 54 years, of whom 783 (68.0%) were male, 559 (48.5%) had traumatic brain injury, and 905 (78.6%) had a GCS-EM greater than 8 before extubation (scores range from 2 to 10). Interventions: None. Measurements and main results: GCS-EM was computed in intubated patients on the day of extubation. The main outcome was extubation failure, defined as unplanned reintubation within 5 days of extubation. Analyses used multilevel logistic regression with adjustment for patient characteristics and a random intercept for hospital site. In the primary analysis, GCS-EM was not associated with extubation failure (odds ratio, 1.07 per additional point; 95% CI, 0.87-1.31). Findings were consistent in sensitivity analyses that: 1) used different adjustment covariates, 2) included a verbal estimate to derive an overall GCS, 3) accounted for missing data, 4) considered a 2-day time interval to define extubation failure, 5) accounted for competing risks, and 6) used a propensity score-based model. There was no association between GCS-EM and extubation outcome in subgroups defined by brain injury diagnosis or age. Conclusions: In this large, contemporary, multicenter cohort of patients with acute brain injury, we found no association between the GCS-EM and odds of extubation failure. However, few patients had a pre-extubation GCS-EM less than or equal to 8, and the possibility of a true prognostic association in patients with low scores is not excluded

Clinical practice and effect of carbon dioxide on outcomes in mechanically ventilated acute brain-injured patients: a secondary analysis of the ENIO study

Purpose: The use of arterial partial pressure of carbon dioxide (PaCO2) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We aimed to describe targets for PaCO2 in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO2 values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO2 with in-hospital mortality. Methods: We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO2 was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO2 &gt; 35 and to 45&nbsp;mmHg; mild hypocapnia as 32-35&nbsp;mmHg; severe hypocapnia as 26-31&nbsp;mmHg, forced hypocapnia as &lt; 26&nbsp;mmHg, and hypercapnia as &gt; 45&nbsp;mmHg. Results: 1476 patients (65.9% male, mean age 52 [Formula: see text] 18&nbsp;years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day&nbsp;during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO2 had a U-shape relationship with in-hospital mortality with only&nbsp;severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus p value = 0.0009). Important differences were observed across different subgroups of ABI patients. Conclusions: Normocapnia and mild hypocapnia are common in ABI patients&nbsp;and do not affect patients' outcome. Extreme derangements of PaCO2 values were significantly associated with increased in-hospital mortality