Early mobilization of patients with subarachnoid haemorrhage: a national survey of french intensive care units.

OBJECTIVE: To describe French intensive care unit practices regarding the mobilization of patients with subarachnoid haemorrhage. DESIGN: A cross-sectional nationwide survey study. SUBJECTS: Intensivists and physiotherapists or nurses from French intensive care units managing patients with subarachnoid haemorrhage. METHODS: An online questionnaire survey was distributed through the Neurocritical Care and Neuro Anesthesiology French Speaking Society. RESULTS: The response rate was 89%. Of these, 90% did not have a mobilization protocol for patients with subarachnoid haemorrhage. Sixteen percent of departments prohibited all forms of motor physiotherapy for a predefined period. Nineteen percent systematically prohibited out-of-bed mobilization, regardless of the severity of subarachnoid haemorrhage and in the absence of any complication, for a predefined period. The main factors that would delay or interrupt physiotherapy prescription were intracranial hypertension (79%), currently treated vasospasm (59%), and suspicion of vasospasm (44%). Ninety-one percent of the centres identified at least one complication that could be associated with standing upright. These mainly included decreased cerebral perfusion (71%), dislodged external ventricular or lumbar derivations (68%), and haemodynamic instability (65%). CONCLUSION: Mobilization of patients with subarachnoid haemorrhage is heterogeneous among French neuro-intensive care units and several barriers preclude improvement of mobilization practices. Interventional studies assessing mobilization practices, as well as education and training of staff, are crucial to ensure the proper management of patients with subarachnoid haemorrhage and to improve outcomes.

Trending Ability of End-Tidal Capnography Monitoring During Mechanical Ventilation to Track Changes in Arterial Partial Pressure of Carbon Dioxide in Critically Ill Patients With Acute Brain Injury: A Monocenter Retrospective Study.

BACKGROUND: Changes in arterial partial pressure of carbon dioxide (Pa co2 ) may alter cerebral perfusion in critically ill patients with acute brain injury. Consequently, international guidelines recommend normocapnia in mechanically ventilated patients with acute brain injury. The measurement of end-tidal capnography (Et co2 ) allows its approximation. Our objective was to report the agreement between trends in Et co2 and Pa co2 during mechanical ventilation in patients with acute brain injury. METHODS: Retrospective monocenter study was conducted for 2 years. Critically ill patients with acute brain injury who required mechanical ventilation with continuous Et co2 monitoring and with 2 or more arterial gas were included. The agreement was evaluated according to the Bland and Altman analysis for repeated measurements with calculation of bias, and upper and lower limits of agreement. The directional concordance rate of changes between Et co2 and Pa co2 was evaluated with a 4-quadrant plot. A polar plot analysis was performed using the Critchley methods. RESULTS: We analyzed the data of 255 patients with a total of 3923 paired ΔEt co2 and ΔPa co2 (9 values per patient in median). Mean bias by Bland and Altman analysis was -8.1 (95 CI, -7.9 to -8.3) mm Hg. The directional concordance rate between Et co2 and Pa co2 was 55.8%. The mean radial bias by polar plot analysis was -4.4° (95% CI, -5.5 to -3.3) with radial limit of agreement (LOA) of ±62.8° with radial LOA 95% CI of ±1.9°. CONCLUSIONS: Our results question the performance of trending ability of Et co2 to track changes in Pa co2 in a population of critically ill patients with acute brain injury. Changes in Et co2 largely failed to follow changes in Pa co2 in both direction (ie, low concordance rate) and magnitude (ie, large radial LOA). These results need to be confirmed in prospective studies to minimize the risk of bias.

Systemic Inflammation Evaluated by Interleukin-6 or C-Reactive Protein in Critically Ill Patients: Results From the FROG-ICU Study.

Background: The prognostic impact of high concentration of interleukin-6 (IL-6) or C-reactive protein (CRP), two routinely available markers of systemic inflammation in the general population of critically ill patients, remains unclear. In a large cohort of critically ill patients including septic and non-septic patients, we assessed the relationship between baseline IL-6 or CRP and mortality, organ dysfunction, and the need for organ support. Methods: This was an ancillary analysis of the prospective French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study including patients with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following intensive care unit (ICU) admission. The primary objective was to determine the association between baseline IL-6 or CRP concentration and survival until day 90. Secondary outcomes included organ dysfunction as evaluated by the Sequential Organ Failure Assessment (SOFA) score, and the need for organ support, including vasopressors/inotropes and/or renal replacement therapy (RRT). Results: Median IL-6 and CRP concentrations (n = 2,076) at baseline were 100.9 pg/ml (IQR 43.5-261.7) and 143.7 mg/L (IQR 78.6-219.8), respectively. Day-90 mortality was 30%. High IL-6 or CRP was associated with worse 90-day survival (hazard ratios 1.92 [1.63-2.26] and 1.21 [1.03-1.41], respectively), after adjustment on the Simplified Acute Physiology Score II (SAPS-II). High IL-6 was also associated with the need for organ-support therapies, such as vasopressors/inotropes (OR 2.67 [2.15-3.31]) and RRT (OR 1.55 [1.26-1.91]), including when considering only patients independent from those supports at the time of IL-6 measurement. Associations between high CRP and organ support were inconsistent. Conclusion: IL-6 appears to be preferred over CRP to evaluate critically ill patients' prognoses.

Timing and causes of death in severe COVID-19 patients.

BACKGROUND: Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). METHODS: We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. RESULTS: From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th-75th IQR, 7-27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th-75th IQR: 7-19 days), while only one death had occurred during the first 3 days since ICU admission. CONCLUSIONS: In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

Comparison of Circulating Immune Cells Profiles and Kinetics Between Coronavirus Disease 2019 and Bacterial Sepsis.

OBJECTIVES: Although clinical presentation of coronavirus disease 2019 has been extensively described, immune response to severe acute respiratory syndrome coronavirus 2 remains yet not fully understood. Similarities with bacterial sepsis were observed; however, few studies specifically addressed differences of immune response between both conditions. Here, we report a longitudinal analysis of the immune response in coronavirus disease 2019 patients, its correlation with outcome, and comparison between severe coronavirus disease 2019 patients and septic patients. DESIGN: Longitudinal, retrospective observational study. SETTING: Tertiary-care hospital during the first 2020 coronavirus disease 2019 outbreak in France. PATIENTS: All successive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the emergency department, medical ward, and ICU with at least one available immunophenotyping performed during hospital stay. MEASUREMENTS AND MAIN RESULTS: Between March and April 2020, 247 patients with coronavirus disease 2019 were included and compared with a historical cohort of 108 severe septic patients. Nonsevere coronavirus disease 2019 patients (n = 153) presented normal or slightly altered immune profiles. Severe coronavirus disease 2019 (n = 94) immune profile differed from sepsis. Coronavirus disease 2019 exhibited profound and prolonged lymphopenia (mostly on CD3, CD4, CD8, and NK cells), neutrophilia, and human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation. Surprisingly, coronavirus disease 2019 patients presented a unique profile of B cells expansion, basophilia, and eosinophilia. Lymphopenia, human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation, and neutrophilia were associated with a worsened outcome, whereas basophilia and eosinophilia were associated with survival. Circulating immune cell kinetics differed between severe coronavirus disease 2019 and sepsis, lack of correction of immune alterations in coronavirus disease 2019 patients during the first 2 weeks of ICU admission was associated with death and nosocomial infections. CONCLUSIONS: Circulating immune cells profile differs between mild and severe coronavirus disease 2019 patients. Severe coronavirus disease 2019 is associated with a unique immune profile as compared with sepsis. Several immune features are associated with outcome. Thus, immune monitoring of coronavirus disease 2019 might be of help for patient management.

Role of Damage-Associated Molecular Patterns in Septic Acute Kidney Injury, From Injury to Recovery.

Damage-associated molecular patterns (DAMPs) are a group of immunostimulatory molecules, which take part in inflammatory response after tissue injury. Kidney-specific DAMPs include Tamm-Horsfall glycoprotein, crystals, and uromodulin, released by tubular damage for example. Non-kidney-specific DAMPs include intracellular particles such as nucleus [histones, high-mobility group box 1 protein (HMGB1)] and cytosol parts. DAMPs trigger innate immunity by activating the NRLP3 inflammasome, G-protein coupled class receptors or the Toll-like receptor. Tubular necrosis leads to acute kidney injury (AKI) in either septic, ischemic or toxic conditions. Tubular necrosis releases DAMPs such as histones and HMGB1 and increases vascular permeability, which perpetuates shock and hypoperfusion via Toll Like Receptors. In acute tubular necrosis, intracellular abundance of NADPH may explain a chain reaction where necrosis spreads from cell to cell. The nature AKI in intensive care units does not have preclinical models that meet a variation of blood perfusion or a variation of glomerular filtration within hours before catecholamine infusion. However, the dampening of several DAMPs in AKI could provide organ protection. Research should be focused on the numerous pathophysiological pathways to identify the relative contribution to renal dysfunction. The therapeutic perspectives could be strategies to suppress side effect of DAMPs and to promote renal function regeneration.

Impact of systematic screening for AmpC-hyperproducing Enterobacterales intestinal carriage in intensive care unit patients.

BACKGROUND: Empirical antimicrobial therapy (EAT) is a challenge for community-acquired, hospital-acquired and ventilator-associated pneumonia, particularly in the context of the increasing occurrence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), including extended-spectrum beta-lactamase Enterobacterales (ESBL-E) and high-level expressed AmpC cephalosporinase-producing Enterobacterales (HLAC-E). To prevent the overuse of broad-spectrum antimicrobial therapies, such as carbapenems, we assessed the performance of screening for intestinal carriage of HLAC-E in addition to ESBL-E to predict 3GCR-E (ESBL-E and/or HLAC-E) presence or absence in respiratory samples in ICU, and to evaluate its potential impact on carbapenem prescription. MATERIALS AND METHODS: This monocentric retrospective observational study was performed in a surgical ICU during a 4-year period (January 2013-December 2016). Patients were included if they had a positive culture on a respiratory sample and a previous intestinal carriage screening performed by rectal swabbing within 21 days. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for the screening for intestinal carriage of ESBL-E, HLAC-E and 3GCR-E (ESBL-E and/or HLAC-E) as predictor of their absence/presence in respiratory samples. Impact of HLAC-E and ESBL-E reporting on EAT was also studied. RESULTS: 765 respiratory samples, retrieved from 468 patients, were analyzed. ESBL-E prevalence was 23.8% in rectal swab and 4.4% in respiratory samples. HLAC-E prevalence was 9.0% in rectal swabs and 3.7% in respiratory samples. Overall, the 3GCR-E prevalence was 31.8% in rectal swabs and 7.7% in respiratory samples. NPVs were 98.8%, 98.0% and 96.6% for ESBL-E, HLAC-E and 3GCR-E, respectively. Over the study period, empirical antimicrobial therapy was initiated for 315 episodes of respiratory infections: 228/315 (72.4%) were associated with negative intestinal carriage screening for both HLAC-E and ESBL-E, of whom 28/228 (12.3%) were treated with carbapenems. Of 23/315 (7.3%) cases with screening for positive intestinal carriage with HLAC-E alone, 10/23 (43.5%) were treated with carbapenems. CONCLUSION: Systematic screening and reporting of HLAC-E in addition to ESBL-E in intestinal carriage screening could help to predict the absence of 3GCR-E in respiratory samples of severe surgical ICU patients. This could improve the appropriateness of EAT in ICU patients with HAP and may prevent the overuse of carbapenems.

Accuracy of a multiparametric score based on pulse wave analysis for prediction of fluid responsiveness: ancillary analysis of an observational study.

PURPOSE: The pressure recording analytical method (PRAM) monitor is a non-invasive pulse contour cardiac output (CO) device that cannot be considered interchangeable with the gold standard for CO estimation. It, however, generates additional hemodynamic indices that need to be evaluated. Our objective was to investigate the performance of a multiparametric predictive score based on a combination of several parameters generated by the PRAM monitor to predict fluid responsiveness. METHODS: Secondary analysis of a prospective observational study from April 2016 to December 2017 in two French teaching hospitals. We included critically ill patients who were monitored by esophageal Doppler monitoring and an invasive arterial line, and received a 250-500 mL crystalloid fluid challenge. The main outcome measure was the predictive score discrimination evaluated by the area under the receiver operating characteristics curve. RESULTS: The three baseline PRAM-derived parameters associated with fluid responsiveness in univariate analysis were pulse pressure variation, cardiac cycle efficiency, and arterial elastance (P < 0.01, P = 0.03, and P < 0.01, respectively). The median [interquartile range] predictive score, calculated after discretization of these parameters according to their optimal threshold value was 3 [2-3] in fluid responders and 1 [1-2] in fluid non-responders, respectively (P < 0.001). The area under the curve of the predictive score was 0.807 (95% confidence interval, 0.662 to 0.909; P < 0.001). CONCLUSION: A multiparametric score combining three parameters generated by the PRAM monitor can predict fluid responsiveness with good positive and negative predictive values in intensive care unit patients.

RéSUMé: OBJECTIF: Le moniteur PRAM (pressure recording analytical method) est un dispositif non invasif de surveillance du débit cardiaque (DC) fondé sur la mesure de contour de l'onde de pouls qui ne peut être considéré comme interchangeable avec la référence de l'estimation du DC. Cependant, ce dispositif génère des indices hémodynamiques supplémentaires qui doivent être évalués. Notre objectif était d'examiner la performance d'un score prédictif multiparamétrique fondé sur une combinaison de plusieurs paramètres générés par le moniteur PRAM afin de prédire la réponse au remplissage volémique. MéTHODE: Analyse secondaire d'une étude observationnelle prospective entre avril 2016 et décembre 2017 dans deux hôpitaux universitaires français. Nous avons inclus des patients en état critique monitorés par un Doppler oesophagien et une ligne artérielle invasive, et ayant reçu un bolus de cristalloïdes de 250­500 mL. Le critère d'évaluation principal était la discrimination du score prédictif telle qu'évaluée par la surface sous la courbe de fonction d'efficacité de l'observateur (ROC). RéSULTATS: Les trois paramètres de base dérivés du PRAM associés à la réponse au remplissage dans l'analyse univariée étaient la variation de pression différentielle, l'efficacité du cycle cardiaque, et l'élastance artérielle (P < 0,01, P = 0,03, et P < 0,01, respectivement). Le score prédictif médian [écart interquartile], calculé après discrétisation de ces paramètres selon leur valeur seuil optimale, était de 3 [2­3] chez les répondeurs au remplissage et de 1 [1­2] chez les non-répondeurs, respectivement (P < 0,001). La surface sous la courbe du score prédictif était de 0,807 (intervalle de confiance 95 %, 0,662 à 0,909; P < 0,001). CONCLUSION: Un score multiparamétrique combinant trois paramètres générés par le moniteur PRAM peut prédire la réponse au remplissage volémique avec de bonnes valeurs prédictives positives et négatives chez les patients à l'unité de soins intensifs.

Sepsis Triggers a Late Expansion of Functionally Impaired Tissue-Vascular Inflammatory Monocytes During Clinical Recovery.

Sepsis is characterized by a systemic inflammation that can cause an immune dysfunction, for which the underlying mechanisms are unclear. We investigated the impact of cecal ligature and puncture (CLP)-mediated polymicrobial sepsis on monocyte (Mo) mobilization and functions. Our results show that CLP led to two consecutive phases of Mo deployment. The first one occurred within the first 3 days after the induction of the peritonitis, while the second phase was of a larger amplitude and extended up to a month after apparent clinical recovery. The latter was associated with the expansion of Mo in the tissue reservoirs (bone marrow and spleen), their release in the blood and their accumulation in the vasculature of peripheral non-lymphoid tissues. It occurred even after antibiotic treatment but relied on inflammatory-dependent pathways and inversely correlated with increased susceptibility and severity to a secondary infection. The intravascular lung Mo displayed limited activation capacity, impaired phagocytic functions and failed to transfer efficient protection against a secondary infection into monocytopenic CCR2-deficient mice. In conclusion, our work unveiled key dysfunctions of intravascular inflammatory Mo during the recovery phase of sepsis and provided new insights to improve patient protection against secondary infections.