Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study.

BACKGROUND: Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors. METHODS: This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed. RESULTS: Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034). CONCLUSION: Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019.

Resilience after severe critical illness: a prospective, multicentre, observational study (RESIREA).

BACKGROUND: Critical-illness survivors may experience post-traumatic stress disorder (PTSD) and quality-of-life impairments. Resilience may protect against psychological trauma but has not been adequately studied after critical illness. We assessed resilience and its associations with PTSD and quality of life, and also identified factors associated with greater resilience. METHODS: This prospective, multicentre, study in patients recruited at 41 French ICUs was done in parallel with the NUTRIREA-3 trial in patients given mechanical ventilation and vasoactive amines for shock. Three months to one year after intensive-care-unit admission, survivors completed the Connor-Davidson Resilience Scale (CD-RISC-25), Impact of Event-Revised scale for PTSD symptoms (IES-R), SF-36 quality-of-life scale, Multidimensional Scale of Perceived Social Support (MSPSS), and Brief Illness Perception Questionnaire (B-IPQ). RESULTS: Of the 382 included patients, 203 (53.1%) had normal or high resilience (CD-RISC-25 ≥ 68). Of these resilient patients, 26 (12.8%) had moderate to severe PTSD symptoms (IES-R ≥ 24) vs. 45 (25.4%) patients with low resilience (p = 0.002). Resilient patients had higher SF-36 scores. Factors independently associated with higher CD-RISC-25 scores were higher MSPSS score indicating stronger social support (OR, 1.027; 95%CI 1.008-1.047; p = 0.005) and lower B-IPQ scores indicating a more threatening perception of the illness (OR, 0.973; 95%CI 0.950-0.996; p = 0.02). CONCLUSIONS: Resilient patients had a lower prevalence of PTSD symptoms and higher quality of life scores, compared to patients with low resilience. Higher scores for social support and illness perception were independently associated with greater resilience. Thus, our findings suggest that interventions to strengthen social support and improve illness perception may help to improve resilience. Such interventions should be evaluated in trials with PTSD mitigation and quality-of-life improvement as the target outcomes.

Perceived Quality of Life in Intensive Care Medicine Physicians: A French National Survey.

Purpose: There is a growing interest in the quality of work life (QWL) of healthcare professionals and staff well-being. We decided to measure the perceived QWL of ICU physicians and the factors that could influence their perception. Methods: We performed a survey coordinated and executed by the French Trade Union of Intensive Care Physicians (SMR). QWL was assessed using the French version of the Work-Related Quality of Life (WRQoL) scale, perceived stress using the French version of 10 item-Perceived Stress Scale (PSS-10) and group functioning using the French version of the Reflexivity Scale, the Social Support at Work Questionnaire (QSSP-P). Results: 308 French-speaking ICU physicians participated. 40% perceived low WRQoL, mainly due to low general well-being, low satisfaction with working conditions and low possibility of managing the articulation between their private and professional lives. Decreased QWL was associated with being a woman (p = .002), having children (p = .022) and enduring many monthly shifts (p = .022). Conclusions: This work highlights the fact that ICU physicians feel a significant imbalance between the demands of their profession and the resources at their disposal. Communication and exchanges within a team and quality of social support appear to be positive elements to maintain and/or develop within our structures.

Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm.

BACKGROUND: Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated. METHODS: We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed. RESULTS: From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, -1.9 percentage points; 95% CI, -8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups. CONCLUSIONS: Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION ClinicalTrials.gov number, NCT01994772.).

Central Venous-to-Arterial PCO2 Difference and Central Venous Oxygen Saturation in the Detection of Extubation Failure in Critically Ill Patients.

OBJECTIVES: To evaluate the ability of central venous-to-arterial carbon dioxide pressure difference, central venous oxygen saturation, and the combination of these two parameters to detect extubation failure in critically ill patients. DESIGN: Multicentric, prospective, observational study. SETTING: Three ICUs. PATIENTS: All patients who received mechanical ventilation for more than 48 hours and tolerated spontaneous breathing trials with a T-piece for 60 minutes. INTERVENTIONS: Extubation after successful spontaneous breathing trials. Extubation failure was defined as the need for mechanical ventilation within 48 hours. MEASUREMENTS AND MAIN RESULTS: The oxygen delivery index, oxygen consumption index, central venous oxygen saturation, central venous-to-arterial carbon dioxide pressure difference, and oxygen extraction were measured immediately before spontaneous breathing trials and at 60 minutes after spontaneous breathing trials initiation. Seventy-five patients were enrolled, and extubation failure was noted in 18 (24%) patients. Oxygen consumption index increased significantly during spontaneous breathing trials in the failure group. Oxygen delivery index increased in both success and failure groups. Oxygen extraction increased in the failure group (p = 0.005) and decreased in the success group (p = 0.001). Central venous oxygen saturation decreased in the failure group and increased in the success group (p = 0.014). ΔPCO2 value increased in the extubation failure group and decreased in the success group (p = 0.002). Changes in ΔPCO2 (Δ - ΔPCO2) and central venous oxygen saturation (ΔScvO2) during spontaneous breathing trials were independently associated with extubation failure (odds ratio, 1.02; 95% CI, 1.01-1.05; p = 0.006, and odds ratio, 0.84; 95% CI, 0.70-0.95; p = 0.02, respectively). Δ - ΔPCO2 and central venous oxygen saturation could predict extubation failure with areas under the curve of 0.865 and 0.856, respectively; however, their combined areas under the curve was better at 0.940. CONCLUSIONS: We found that Δ - ΔPCO2 and central venous oxygen saturation, during spontaneous breathing trials, were independent predictors of weaning outcomes. Combination analysis of both parameters enhanced their diagnostic performance and provided excellent predictability in extubation failure detection in critically ill patients.

Risk factors and events in the adult intensive care unit associated with pain as self-reported at the end of the intensive care unit stay.

BACKGROUND: The short-term and long-term consequences of the most frequent painful procedures performed in the ICU are unclear. This study aimed to identify the risk factors associated with pain-related discomfort perceived by critically ill patients during the whole ICU stay as self-reported by patients at the end of their ICU stay. METHODS: The study involved 34 ICUs. Adult patients who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Discomforts, including the pain-related discomfort, were assessed using the French 18-item questionnaire on discomfort in ICU patients, the "Inconforts des Patients de REAnimation" (IPREA). Patients scored each item from 0 (minimal discomfort) to 10 (maximal discomfort). Associations between patient characteristics at ICU admission, life support therapies and main potentially painful procedures performed during the ICU stay and pain-related discomfort scores assessed at the end of the ICU stay were analyzed. RESULTS: Patients with complete IPREA questionnaires (n = 2130) were included. The median pain-related discomfort score was 3 (IQR 0-5). From the univariate analysis, pain-related discomfort scores were negatively correlated with age and positively correlated with ICU stay duration; surgical patients reported significant higher pain-related discomfort scores than medical patients; chest drain insertion, chest drain removal, use of bladder catheter, central venous catheter (CVC) insertion, complex dressing change, and intra-hospital transport were associated with pain-related discomfort scores. From the multivariate analyses using generalized estimating equations models, only age, chest drain removal, use of a bladder catheter, CVC insertion, and intra-hospital transport were the main risk factors associated with pain-related discomfort scores. CONCLUSION: Patients who underwent chest drain removal, bladder catheter, CVC insertion, and intra-hospital transport during their ICU stay reported higher pain-related discomfort scores (with respect to the whole ICU stay and assessed at the end of their ICU stay) than patients who did not experience these events. This study may pave the way for further targeted studies aiming at investigating a causal link between these common procedures in the ICU and adult critically ill patients' perceptions of their ICU stay regarding recalled pain. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934, retrospectively registered on May 13, 2015.

Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2).

BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099. FINDINGS: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04). INTERPRETATION: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition. FUNDING: La Roche-sur-Yon Departmental Hospital and French Ministry of Health.

Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial.

BACKGROUND: Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. METHODS: Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. RESULTS: A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). CONCLUSIONS: Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03411447 . Registered 18 July 2017. Retrospectively registered.

Assessment of patients' self-perceived intensive care unit discomforts: Validation of the 18-item version of the IPREA.

BACKGROUND AND AIMS: We reported the validation of the 18-item version of the 'Inconforts des Patients de REAnimation (IPREA)' questionnaire that includes 2 new items exploring feeling depressed and shortness of breath during an intensive care unit (ICU) stay. METHODS: The validation process was integrated in a multicenter, cluster-randomized, controlled, two-parallel group study built to assess the effectiveness of a tailored multicomponent program for reducing self-perceived discomfort in the ICU. All patients aged 18 years or older who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Data collection included demographics (sex, age), type of admission (medical and surgical), health status scores at admission (Knaus score and McCabe index, Simplified Acute Physiology Score (SAPS) II), specific ICU therapeutics such as mechanical ventilation (MV), noninvasive ventilation (NIV), use of vasopressors, or renal replacement therapy (RRT), and ICU stay duration. RESULTS: A total of 994 patients were included. The initial structure of IPREA was confirmed using confirmatory factor analysis showing satisfactory fit (RMSEA at 0.042, CFI at 0.912). No multidimensional structure was identified, allowing the calculation of an overall discomfort score. The three highest discomforts were sleep deprivation, thirst, and perfusion lines and other devices, and the 3 lowest discomforts were limited visiting hours, hunger, and isolation. The overall discomfort score of the 18-item version of IPREA did not differ between men and women. Higher age was significantly correlated with a lower overall discomfort score. While MV was not linked to self-reported discomfort, patients treated by NIV reported higher overall discomfort scores than patients not treated by NIV. CONCLUSION: The 18-item version of IPREA is easy to use and possesses satisfactory psychometric properties. The availability of a reliable and valid French questionnaire asking about patients' self-perceived ICU discomforts enables feedback from the health care team to be incorporated in a continuous quality health care improvement strategy. TRIAL REGISTRATION: clinicaltrial.gov NCT02442934 (registration date: May 18, 2015, retrospectively registered).

One-year mortality in patients requiring prolonged mechanical ventilation: multicenter evaluation of the ProVent score.

INTRODUCTION: Current severity-of-illness indexes are unable to assess the long-term prognosis of patients requiring prolonged mechanical ventilation. A prognostic scoring system (Prognosis for Prolonged Ventilation score - ProVent - score) seems able to evaluate one-year mortality of such patients. However, testing of the model outside the developers' centers has not been reported. So, it is unclear how the ProVent score performs in non-US and non-tertiary ICUs. The goal of our study was to evaluate its performances in a French multicenter, community hospital-based setting. METHODS: In three primary ICUs, 201 patients requiring mechanical ventilation for at least 21 days were enrolled in a retrospective cohort study. ICU mortality was abstracted from medical records and, for patients discharged alive from the ICU, one-year mortality was determined by telephone calls to patients' general practitioners. RESULTS: One-year mortality was 60% (n = 120). On day 21 of ventilation, ProVent score value was 0 in 19 patients (9%), 1 in 63 patients (31%), 2 in 64 patients (32%), 3 in 37 patients (18%), and ≥4 in 18 patients (9%), respectively. For ProVent score values ranging from 0 to ≥4, one-year mortality rates were 21%, 43%, 67%, 78%, and 94%, respectively. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve for the ProVent score was 0.74 (95% confidence interval 0.671 to 0.809). Stepwise logistic regression analysis showed that only three variables (age ≥65 years, vasopressors, and hemodialysis) were independently associated with one-year mortality in our population. In assigning one point to each variable, we created a French ProVent score. The Hosmer-Lemeshow goodness-of-fit statistic was 1.36 (DF = 6, P = 0.857) and the AUC of the ROC curve was 0.742 (95% confidence interval 0.673 to 0.810). One-year mortality rates for French ProVent score ranging from 0 to 3 were 34.6%, 70.9%, 83.3% and 100%, respectively (P <0.0001). CONCLUSIONS: The ProVent score is able, even in non-US ICUs and in community hospitals, to accurately identify among patients requiring prolonged mechanical ventilation those who are at high risk of one-year mortality. Its simplification appears possible. However, further validation of this French ProVent score in a larger external sample is indicated.

Central venous-to-arterial carbon dioxide partial pressure difference in early resuscitation from septic shock: a prospective observational study.

BACKGROUND: Central venous-to-arterial carbon dioxide partial pressure difference (ΔPCO2) can be used as a marker for the efficacy of venous blood in removing the total CO2 produced by the tissues. To date, this role of ΔPCO2 has been assessed only in patients after resuscitation from septic shock with already normalised central venous oxygen saturation (ScvO2 ≥70%). There are no reports on the behaviour of ΔPCO2 and its relationship to cardiac index (CI) and clinical outcome before normal ScvO2 has been achieved. OBJECTIVES: To investigate the behaviour of ΔPCO2 and its relationship to CI, blood lactate concentration and 28-day mortality during resuscitation in the very early phase of septic shock. To examine whether patients who normalise both ΔPCO2 and ScvO2 during the first 6  h of resuscitation will have a greater percentage decrease in blood lactate concentration than those who only achieve normal ScvO2. DESIGN: Prospective observational study. SETTING: Intensive Care Unit (ICU) in a university hospital. PATIENTS: Eighty patients with septic shock were consecutively recruited. INTERVENTIONS: Patients were resuscitated in accordance with the recommendations of the Surviving Sepsis Campaign. MAIN OUTCOME MEASURES: Blood lactate concentrations, and haemodynamic and oxygen-derived variables were obtained at ICU admission (T0) and 6  h after admission (T6). Lactate decrease was defined as the percentage decrease in lactate concentration from T0 to T6. All cause 28-day mortality was also recorded. RESULTS: Data are presented as median (interquartile range). At T0, there were significant differences (P < 0.0001) between normal (ΔPCO2 ≤0.8 kPa) and high ΔPCO2 groups for CI (3.9 [3.3 to 4.7] vs. 2.9 [2.3 to 3.1] l min m) and ScvO2 (73 [65 to 80] vs. 61 [53 to 63]%). The correlation between changes in CI and ΔPCO2 was r  =  -0.62, P < 0.0001. Patients who reached a normal ΔPCO2 at T6 had larger decreases in blood lactate concentration and Sequential Organ Failure Assessment scores on day 1. The lactate decrease was greatest in the subgroup achieving both normal ScvO2 and ΔPCO2 at T6. Lactate decrease, unlike ΔPCO2 and ScvO2, was an independent predictor of 28-day mortality. CONCLUSION: Monitoring ΔPCO2 may be a useful tool to assess the adequacy of tissue perfusion during resuscitation. The normalisation of both ΔPCO2 and ScvO2 is associated with a greater decrease in blood lactate concentration than ScvO2 alone. The lactate decrease is an independent predictor of 28-day mortality. Further research is needed to confirm this hypothesis.

Renal replacement therapy initiation strategies in comatose patients with severe acute kidney injury: a secondary analysis of a multicenter randomized controlled trial.

PURPOSE: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI. METHODS: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization. RESULTS: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results. CONCLUSION: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.

Effects of sitting position and applied positive end-expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechanical ventilation*.

OBJECTIVE: To evaluate the extent to which sitting position and applied positive end-expiratory pressure improve respiratory mechanics of severely obese patients under mechanical ventilation. DESIGN: Prospective cohort study. SETTINGS: A 15-bed ICU of a tertiary hospital. PARTICIPANTS: Fifteen consecutive critically ill patients with a body mass index (the weight in kilograms divided by the square of the height in meters) above 35 were compared to 15 controls with body mass index less than 30. INTERVENTIONS: Respiratory mechanics was first assessed in the supine position, at zero end-expiratory pressure, and then at positive end-expiratory pressure set at the level of auto-positive endexpiratory pressure. Second, all measures were repeated in the sitting position. MEASUREMENTS AND MAIN RESULTS: Assessment of respiratory mechanics included plateau pressure, auto-positive end-expiratory pressure, and flow-limited volume during manual compression of the abdomen, expressed as percentage of tidal volume to evaluate expiratory flow limitation. In supine position at zero end-expiratory pressure, all critically ill obese patients demonstrated expiratory flow limitation (flow-limited volume, 59.4% [51.3-81.4%] vs 0% [0-0%] in controls; p < 0.0001) and greater auto-positive end-expiratory pressure (10 [5-12.5] vs 0.7 [0.4-1.25] cm H2O in controls; p < 0.0001). Applied positive end-expiratory pressure reverses expiratory flow limitation (flow-limited volume, 0% [0-21%] vs 59.4% [51-81.4%] at zero end-expiratory pressure; p < 0.001) in almost all the obese patients, without increasing plateau pressure (24 [19-25] vs 22 [18-24] cm H2O at zero end-expiratory pressure; p = 0.94). Sitting position not only reverses partially or completely expiratory flow limitation at zero end-expiratory pressure (flow-limited volume, 0% [0-58%] vs 59.4% [51-81.4%] in supine obese patients; p < 0.001) but also results in a significant drop in auto-positive end-expiratory pressure (1.2 [0.6-4] vs 10 [5-12.5] cm H2O in supine obese patients; p < 0.001) and plateau pressure (15.6 [14-17] vs 22 [18-24] cm H2O in supine obese patients; p < 0.001). CONCLUSIONS: In critically ill obese patients under mechanical ventilation, sitting position constantly and significantly relieved expiratory flow limitation and auto-positive end-expiratory pressure resulting in a dramatic drop in alveolar pressures. Combining sitting position and applied positive end-expiratory pressure provides the best strategy.

Rescue therapy by switching to total face mask after failure of face mask-delivered noninvasive ventilation in do-not-intubate patients in acute respiratory failure.

OBJECTIVE: To evaluate the impact of switching to total face mask in cases where face mask-delivered noninvasive mechanical ventilation has already failed in do-not-intubate patients in acute respiratory failure. DESIGN AND SETTING: Prospective observational study in an ICU and a respiratory stepdown unit over a 12-month study period. INTERVENTION: Switching to total face mask, which covers the entire face, when noninvasive mechanical ventilation using facial mask (oronasal mask) failed to reverse acute respiratory failure. PATIENTS: Seventy-four patients with a do-not-intubate order and treated by noninvasive mechanical ventilation for acute respiratory failure. MAIN RESULTS: Failure of face mask-delivered noninvasive mechanical ventilation was associated with a three-fold increase in in-hospital mortality (36% vs. 10.5%; p = 0.009). Nevertheless, 23 out of 36 patients (64%) in whom face mask-delivered noninvasive mechanical ventilation failed to reverse acute respiratory failure and, therefore, switched to total face mask survived hospital discharge. Reasons for switching from facial mask to total face mask included refractory hypercapnic acute respiratory failure (n = 24, 66.7%), painful skin breakdown or facial mask intolerance (n = 11, 30%), and refractory hypoxemia (n = 1, 2.7%). In the 24 patients switched from facial mask to total face mask because of refractory hypercapnia, encephalopathy score (3 [3-4] vs. 2 [2-3]; p < 0.0001), PaCO2 (87 ± 25 mm Hg vs. 70 ± 17 mm Hg; p < 0.0001), and pH (7.24 ± 0.1 vs. 7.32 ± 0.09; p < 0.0001) significantly improved after 2 hrs of total face mask-delivered noninvasive ventilation. Patients switched early to total face mask (in the first 12 hrs) developed less pressure sores (n = 5, 24% vs. n = 13, 87%; p = 0.0002), despite greater length of noninvasive mechanical ventilation within the first 48 hrs (44 hrs vs. 34 hrs; p = 0.05) and less protective dressings (n = 2, 9.5% vs. n = 8, 53.3%; p = 0.007). The optimal cutoff value for face mask-delivered noninvasive mechanical ventilation duration in predicting facial pressure sores was 11 hrs (area under the receiver operating characteristic curve, 0.86 ± 0.04; 95% confidence interval 0.76-0.93; p < 0.0001; sensitivity, 84%; specificity, 71%). CONCLUSION: In patients in hypercapnic acute respiratory failure, for whom escalation to intubation is deemed inappropriate, switching to total face mask can be proposed as a last resort therapy when face mask-delivered noninvasive mechanical ventilation has already failed to reverse acute respiratory failure. This strategy is particularly adapted to provide prolonged periods of continuous noninvasive mechanical ventilation while preventing facial pressure sores.

Defining metabolic acidosis in patients with septic shock using Stewart approach.

PURPOSE: The aim of this study was to define the nature of metabolic acidosis in patients with septic shock on admission to intensive care unit (ICU) using Stewart method. We also aimed to compare the ability of standard base excess (SBE), anion gap (AG), and corrected AG for albumin and lactate (AGcorr) to accurately predict the presence of unmeasured anions (UA). PATIENTS AND METHODS: Thirty consecutive patients with septic shock were prospectively included on ICU admission. Stewart equations modified by Figge were used to calculate the strong ion difference and the strong ion gap (SIG). RESULTS: Most patients had multiple underlying mechanisms explaining the metabolic acidosis. Unmeasured anions and hyperchloremia were present in 70% of the patients. Increased UA were present in 23% of patients with normal values of SBE and [HCO3-]. In these patients, plasma [Cl-] was significantly lower compared with patients with low SBE and increased UA (103 [102-106.6] vs 108 [106-111] mmol/L; P=.01, respectively). Corrected AG for albumin and lactate had the best correlation with SIG (r²=0.94; P<.0001) with good agreement (bias, 0, and precision, 1.22) and highest area under the receiver operating characteristic curve (0.995; 95% confidence interval, 0.87-1) to discriminate SIG acidosis. CONCLUSIONS: Patients with septic shock exhibit a complex metabolic acidosis at ICU admission. High UA may be present with normal values of SBE and [HCO3-] as a result of associated "relative" hypochloremic alkalosis. Corrected AG for albumin and lactate offers the most accurate bedside alternative to Stewart calculation of UA.

Outcomes of mild-to-moderate postresuscitation shock after non-shockable cardiac arrest and association with temperature management: a post hoc analysis of HYPERION trial data.

BACKGROUND: Outcomes of postresuscitation shock after cardiac arrest can be affected by targeted temperature management (TTM). A post hoc analysis of the "TTM1 trial" suggested higher mortality with hypothermia at 33 °C. We performed a post hoc analysis of HYPERION trial data to assess potential associations linking postresuscitation shock after non-shockable cardiac arrest to hypothermia at 33 °C on favourable functional outcome. METHODS: We divided the patients into groups with vs. without postresuscitation (defined as the need for vasoactive drugs) shock then assessed the proportion of patients with a favourable functional outcome (day-90 Cerebral Performance Category [CPC] 1 or 2) after hypothermia (33 °C) vs. controlled normothermia (37 °C) in each group. Patients with norepinephrine or epinephrine > 1 µg/kg/min were not included. RESULTS: Of the 581 patients included in 25 ICUs in France and who did not withdraw consent, 339 had a postresuscitation shock and 242 did not. In the postresuscitation-shock group, 159 received hypothermia, including 14 with a day-90 CPC of 1-2, and 180 normothermia, including 10 with a day-90 CPC of 1-2 (8.81% vs. 5.56%, respectively; P = 0.24). After adjustment, the proportion of patients with CPC 1-2 also did not differ significantly between the hypothermia and normothermia groups (adjusted hazards ratio, 1.99; 95% confidence interval, 0.72-5.50; P = 0.18). Day-90 mortality was comparable in these two groups (83% vs. 86%, respectively; P = 0.43). CONCLUSIONS: After non-shockable cardiac arrest, mild-to-moderate postresuscitation shock at intensive-care-unit admission did not seem associated with day-90 functional outcome or survival. Therapeutic hypothermia at 33 °C was not associated with worse outcomes compared to controlled normothermia in patients with postresuscitation shock. Trial registration ClinicalTrials.gov, NCT01994772.

Targeted Temperature Management After In-Hospital Cardiac Arrest: An Ancillary Analysis of Targeted Temperature Management for Cardiac Arrest With Nonshockable Rhythm Trial Data.

BACKGROUND: Targeted temperature management (TTM) currently is the only treatment with demonstrated efficacy in attenuating the harmful effects on the brain of ischemia-reperfusion injury after cardiac arrest. However, whether TTM is beneficial in the subset of patients with in-hospital cardiac arrest (IHCA) remains unclear. RESEARCH QUESTION: Is TTM at 33 °C associated with better neurological outcomes after IHCA in a nonshockable rhythm compared with targeted normothermia (TN; 37 °C)? STUDY DESIGN AND METHODS: We performed a post hoc analysis of data from the published Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm randomized controlled trial in 584 patients. We included the 159 patients with IHCA; 73 were randomized to 33 °C treatment and 86 were randomized to 37 °C treatment. The primary outcome was survival with a good neurologic outcome (cerebral performance category [CPC] score of 1 or 2) on day 90. Mixed multivariate adjusted logistic regression analysis was performed to determine whether survival with CPC score of 1 or 2 on day 90 was associated with type of temperature management after adjustment on baseline characteristics not balanced by randomization. RESULTS: Compared with TN for 48 h, hypothermia at 33 °C for 24 h was associated with a higher percentage of patients who were alive with good neurologic outcomes on day 90 (16.4% vs 5.8%; P = .03). Day 90 mortality was not significantly different between the two groups (68.5% vs 76.7%; P = .24). By mixed multivariate analysis adjusted by Cardiac Arrest Hospital Prognosis score and circulatory shock status, hypothermia was associated significantly with good day 90 neurologic outcomes (OR, 2.40 [95% CI, 1.17-13.03]; P = .03). INTERPRETATION: Hypothermia at 33 °C was associated with better day 90 neurologic outcomes after IHCA in a nonshockable rhythm compared with TN. However, the limited sample size resulted in wide CIs. Further studies of patients after cardiac arrest resulting from any cause, including IHCA, are needed.

High-flow nasal oxygen alone or alternating with non-invasive ventilation in critically ill immunocompromised patients with acute respiratory failure: a randomised controlled trial.

BACKGROUND: Although non-invasive ventilation (NIV) is recommended for immunocompromised patients with acute respiratory failure in the intensive care unit (ICU), it might have deleterious effects in the most severe patients. High-flow nasal oxygen (HFNO) alone might be an alternative method to reduce mortality. We aimed to determine whether HFNO alone could reduce the rate of mortality at day 28 compared with HFNO alternated with NIV. METHODS: FLORALI-IM is a multicentre, open-label, randomised clinical trial conducted in 29 ICUs (28 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure, defined as respiratory rate of 25 breaths per min or more and a partial pressure of arterial oxygen to inspired fraction of oxygen ratio of 300 mm Hg or lower, were randomly assigned (1:1) to HFNO alone (HFNO alone group) or NIV alternating with HFNO (NIV group). Key exclusion criteria were severe hypercapnia above 50 mm Hg, patients who could strongly benefit from NIV (ie, those with underlying chronic lung disease, with cardiogenic pulmonary oedema, or who were postoperative), severe shock, impaired consciousness defined as Glasgow coma score ≤12, urgent need for intubation, do not intubate order, and contraindication to NIV. Patients were assigned using computer-generated permuted blocks and were stratified according to centre and to the type of immunosuppression using a centralised web-based management system. In the HFNO alone group, patients were continuously treated by HFNO with a gas flow rate of 60 L/min or the highest tolerated. In the NIV group, patients were treated with NIV with a first session of at least 4 h, and then by sessions for a minimal duration of 12 h a day, with a dedicated ventilator, targeting a tidal volume below 8 mL/kg of predicted bodyweight, and with a positive end-expiratory level of at least 8 cm H2O. NIV sessions were interspaced with HFNO delivered as in the HFNO alone group. The primary outcome was mortality at day 28 and was assessed in the intention-to-treat population. Secondary outcomes were mortality in the ICU, in hospital, at day 90 and at day 180, intubation at day 28, length of stay in the ICU and in hospital, number of ventilator-free days at day 28, number of oxygenation technique-free days at day 28, and efficacy and tolerance of oxygenation techniques. The trial is registered with ClinicalTrials.gov, NCT02978300, and is complete. FINDINGS: Between Jan 21, 2017 to March 4, 2019, of 497 eligible patients, 300 were randomly assigned but one patient withdrew consent, leaving 299 patients included in the intention-to-treat analysis (154 assigned to the HFNO alone group and 145 assigned to NIV group). Mortality rate at day 28 was 36% (95% CI 29·2 to 44·2; 56 of 154 patients) in the HFNO alone group and 35% (27·9 to 43·2; 51 of 145 patients) in the NIV group (absolute difference 1·2% [95% CI -9·6 to 11·9]; p=0·83). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of HFNO than with NIV (-4 mm on visual analogic scale [IQR -18 to 4] vs 0 mm [-16 to 17]; p=0·040). INTERPRETATION: In critically ill immunocompromised patients with acute respiratory failure, the mortality rate did not differ between HFNO alone and NIV alternating with HFNO. However, study power was limited, so results should be interpreted with caution. FUNDING: French Ministry of Health.

Factors associated with acute mesenteric ischemia among critically ill ventilated patients with shock: a post hoc analysis of the NUTRIREA2 trial.

PURPOSE: Acute mesenteric ischemia (AMI) is a rare, but life-threatening condition occurring among critically ill patients. Several factors have been associated with AMI, but the causal link is debated, most studies being retrospective. Among these factors, enteral nutrition (EN) could be associated with AMI, in particular among patients with shock. We aimed to study the factors independently associated with AMI in a post hoc analysis of the NUTRIREA-2 trial including 2410 critically ill ventilated patients with shock, randomly assigned to receive EN or parenteral nutrition (PN). METHODS: Post hoc analysis of the NUTRIREA-2 trial was conducted. Ventilated adults with shock were randomly assigned to receive EN or PN. AMI was assessed by computed tomography, endoscopy, or laparotomy. Factors associated with AMI were studied by univariate and multivariate analysis. RESULTS: 2410 patients from 44 French intensive care units (ICUs) were included in the study: 1202 patients in the enteral group and 1208 patients in the parenteral group. The median age was 67 [58-76] years, with 67% men, a SAPS II score of 59 [46-74], and a medical cause for ICU admission in 92.7%. AMI was diagnosed among 24 (1%) patients, mainly by computed tomography (79%) or endoscopy (38%). The mechanism of AMI was non-occlusive mesenteric ischemia (n = 12), occlusive (n = 4), and indeterminate (n = 8). The median duration between inclusion in the trial and AMI diagnosis was 4 [1-11] days. Patients with AMI were older, had a higher SAPS II score at ICU admission, had higher plasma lactate, creatinine, and ASAT concentrations and lower hemoglobin concentration, had more frequently EN, dobutamine, and CVVHDF at inclusion, developed more frequently bacteremia during ICU stay, and had higher 28-day and 90-day mortality rates compared with patients without AMI. By multivariate analysis, AMI was independently associated with EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin concentration ≤ 10.9 g/dL. CONCLUSION: Among critically ill ventilated patients with shock, EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin ≤ 10.9 g/dL were independently associated with AMI. Among critically ill ventilated patients requiring vasopressors, EN should be delayed or introduced cautiously in case of low cardiac output requiring dobutamine and/or in case of multiple organ failure with high SAPS II score.