Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol.

Cerebral microdialysis (CMD) catheters allow continuous monitoring of patients' cerebral metabolism in severe traumatic brain injury (TBI). The catheters consist of a terminal semi-permeable membrane that is inserted into the brain's interstitium to allow perfusion fluid to equalize with the surrounding cerebral extracellular environment before being recovered through a central non-porous channel. However, it is unclear how far recovered fluid and suspended metabolites have diffused from within the brain, and therefore what volume or region of brain tissue the analyses of metabolism represent. We assessed diffusion of the small magnetic resonance (MR)-detectible molecule gadobutrol from microdialysis catheters in six subjects (complete data five subjects, incomplete data one subject) who had sustained a severe TBI. Diffusion pattern and distance in cerebral white matter were assessed using T1 (time for MR spin-lattice relaxation) maps at 1 mm isotropic resolution in a 3 Tesla MR scanner. Gadobutrol at 10 mmol/L diffused from cerebral microdialysis catheters in a uniform spheroidal (ellipsoid of revolution) pattern around the catheters' semipermeable membranes, and across gray matter-white matter boundaries. Evidence of gadobutrol diffusion was found up to a mean of 13.4 ± 0.5 mm (mean ± standard deviation [SD]) from catheters, but with a steep concentration drop off so that ≤50% of maximum concentration was achieved at ∼4 mm, and ≤10% of maximum was found beyond ∼7 mm from the catheters. There was little variation between subjects. The relaxivity of gadobutrol in human cerebral white matter was estimated to be 1.61 ± 0.38 L.mmol-1sec-1 (mean ± SD); assuming gadobutrol remained extracellular thereby occupying 20% of total tissue volume (interstitium), and concentration equilibrium with perfusion fluid was achieved immediately adjacent to catheters after 24 h of perfusion. No statistically significant change was found in the concentration of the extracellular metabolites glucose, lactate, pyruvate, nor the lactate/pyruvate ratio during gadobutrol perfusion when compared with period of baseline microdialysis perfusion. Cerebral microdialysis allows continuous monitoring of regional cerebral metabolism-the volume of which is now clearer from this study. It also has the potential to deliver small molecule therapies to focal pathologies of the human brain. This study provides a platform for future development of new catheters optimally designed to treat such conditions.

Clinical evaluation of the BioFire Respiratory Pathogen Panel for the guidance of empirical antimicrobial therapy in critically ill patients with hospital-acquired pneumonia: A multicenter, quality improvement project.

BACKGROUND: We aimed to determine whether implementing antimicrobial stewardship based on multiplex bacterial PCR examination of respiratory fluid can enhance outcomes of critically ill patients with hospital-acquired pneumonia (HAP). METHODS: We conducted a quality improvement study in two hospitals in France. Adult patients requiring invasive mechanical ventilation with a diagnosis of HAP were included. In the pre-intervention period (August 2019 to April 2020), antimicrobial therapy followed European guidelines. In the «intervention¼ phase (June 2020 to October 2021), treatment followed a multiplex PCR-guided protocol. The primary endpoint was a composite endpoint made of mortality on day 28, clinical cure between days 7 and 10, and duration of invasive mechanical ventilation on day 28. The primary outcome was analyzed with a DOOR strategy. RESULTS: A total of 443 patients were included in 3 ICUs from 2 hospitals (220 pre-intervention; 223 intervention). No difference in the ranking of the primary composite outcome was found (DOOR: 50.3%; 95%CI, 49.9%-50.8%). The number of invasive mechanical ventilation-free days at day 28 was 10.0 [0.0; 19.0] in the baseline period and 9.0 [0.0; 20.0] days during the intervention period (p = 0.95). The time-to-efficient antimicrobial treatment was 0.43 ± 1.29 days before versus 0.55 ± 1.13 days after the intervention (p = 0.56). CONCLUSION: Implementation of Rapid Multiplex PCR to guide empirical antimicrobial therapy for critically ill patients with HAP was not associated with better outcomes. However, adherence to stewardship was low, and the study may have had limited power to detect a clinically important difference.

Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study.

BACKGROUND: Unfractionated heparin, administered during venoarterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depends on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation; however, its association with acquired antithrombin deficiency is poorly understood. The objective of this study was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. The hypothesis was that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. METHODS: Adults receiving venoarterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3 to 0.5 IU/ml). For each patient, arterial blood was withdrawn into citrate-containing tubes at 11 time points (from hour 0 up to day 7). Anti-Xa (without dextran or antithrombin added) and antithrombin levels were measured. The primary outcome was the antithrombin plasma level. In the absence of consensus, antithrombin deficiency was defined as a time-weighted average of antithrombin less than or equal to 70%. Data regarding clinical management and heparin dosage were collected. RESULTS: Fifty patients, including 42% postcardiotomy, were included between April 2020 and May 2021, with a total of 447 samples. Median extracorporeal membrane oxygenation duration was 7 (interquartile range, 4 to 12) days. Median antithrombin level was 48% (37 to 60%) at baseline. Antithrombin levels significantly increased throughout the follow-up. Time-weighted average of antithrombin levels was 63% (57 to 73%) and was less than or equal to 70% in 32 (64%) of patients. Overall, 45 (90%) patients had at least one antithrombin value less than 70%, and 35 (70%) had at least one antithrombin value less than 50%. Antithrombin levels were not significantly associated with heparin responsiveness evaluated by anti-Xa assay or heparin dosage. CONCLUSIONS: Venoarterial extracorporeal membrane oxygenation support was associated with a moderate acquired antithrombin deficiency, mainly during the first 72 h, that did not correlate with heparin responsiveness.

Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial.

BACKGROUND: Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation. METHODS: PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with ClinicalTrials.gov, NCT02265406. FINDINGS: From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] vs 51 [32%]; hazard ratio 0·60 [95% CI 0·38-0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone. INTERPRETATION: In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation. FUNDING: French Ministry of Social Affairs and Health.

Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.

BACKGROUND: Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months. METHODS: We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO2 monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO2 (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed. FINDINGS: Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO2 monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO2 group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO2 monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO2 group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO2 group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO2 group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest. INTERPRETATION: After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO2 group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission. FUNDING: The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.

A Deep Learning-Based Automated Framework for Subpeak Designation on Intracranial Pressure Signals.

The intracranial pressure (ICP) signal, as monitored on patients in intensive care units, contains pulses of cardiac origin, where P1 and P2 subpeaks can often be observed. When calculable, the ratio of their relative amplitudes is an indicator of the patient's cerebral compliance. This characterization is particularly informative for the overall state of the cerebrospinal system. The aim of this study is to develop and assess the performances of a deep learning-based pipeline for P2/P1 ratio computation that only takes a raw ICP signal as an input. The output P2/P1 ratio signal can be discontinuous since P1 and P2 subpeaks are not always visible. The proposed pipeline performs four tasks, namely (i) heartbeat-induced pulse detection, (ii) pulse selection, (iii) P1 and P2 designation, and (iv) signal smoothing and outlier removal. For tasks (i) and (ii), the performance of a recurrent neural network is compared to that of a convolutional neural network. The final algorithm is evaluated on a 4344-pulse testing dataset sampled from 10 patient recordings. Pulse selection is achieved with an area under the curve of 0.90, whereas the subpeak designation algorithm identifies pulses with a P2/P1 ratio > 1 with 97.3% accuracy. Although it still needs to be evaluated on a larger number of labeled recordings, our automated P2/P1 ratio calculation framework appears to be a promising tool that can be easily embedded into bedside monitoring devices.

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

Outcomes in Patients With COVID-19 With Acute Encephalopathy and Coma: An International Prospective Study.

BACKGROUND AND OBJECTIVES: To report the prevalence of acute encephalopathy and outcomes in patients with severe coronavirus disease 2019 (COVID-19) and to identify determinants of 90-day outcomes. METHODS: Data from adults with severe COVID-19 and acute encephalopathy were prospectively collected for patients requiring intensive care unit management in 31 university or university-affiliated intensive care units in 6 countries (France, United States, Colombia, Spain, Mexico, and Brazil) between March and September of 2020. Acute encephalopathy was defined, as recently recommended, as subsyndromal delirium or delirium or as a comatose state in case of severely decreased level of consciousness. Logistic multivariable regression was performed to identify factors associated with 90-day outcomes. A Glasgow Outcome Scale-Extended (GOS-E) score of 1-4 was considered a poor outcome (indicating death, vegetative state, or severe disability). RESULTS: Of 4,060 patients admitted with COVID-19, 374 (9.2%) experienced acute encephalopathy at or before the intensive care unit (ICU) admission. A total of 199/345 (57.7%) patients had a poor outcome at 90-day follow-up as evaluated by the GOS-E (29 patients were lost to follow-up). On multivariable analysis, age older than 70 years (odds ratio [OR] 4.01, 95% CI 2.25-7.15), presumed fatal comorbidity (OR 3.98, 95% CI 1.68-9.44), Glasgow coma scale score <9 before/at ICU admission (OR 2.20, 95% CI 1.22-3.98), vasopressor/inotrope support during ICU stay (OR 3.91, 95% CI 1.97-7.76), renal replacement therapy during ICU stay (OR 2.31, 95% CI 1.21-4.50), and CNS ischemic or hemorrhagic complications as acute encephalopathy etiology (OR 3.22, 95% CI 1.41-7.82) were independently associated with higher odds of poor 90-day outcome. Status epilepticus, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome were associated with lower odds of poor 90-day outcome (OR 0.15, 95% CI 0.03-0.83). DISCUSSION: In this observational study, we found a low prevalence of acute encephalopathy at ICU admission in patients with COVID-19. More than half of patients with COVID-19 presenting with acute encephalopathy had poor outcomes as evaluated by GOS-E. Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology. TRIAL REGISTRATION INFORMATION: The study is registered with ClinicalTrials.gov, number NCT04320472.

Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

PURPOSE: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. METHODS: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. RESULTS: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. CONCLUSIONS: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.

Anaesthetic and peri-operative management for thrombectomy procedures in stroke patients.

PURPOSE: To provide recommendations for the anaesthetic and peri-operative management for thrombectomy procedure in stroke patients DESIGN: A consensus committee of 15 experts issued from the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation, SFAR), the Association of French-language Neuro-Anaesthetists (Association des Neuro-Anesthésistes Réanimateurs de Langue Francaise, ANARLF), the French Neuro-Vascular Society (Société Francaise de Neuro-Vasculaire, SFNV), the French Neuro-Radiology Society (Société Francaise de Neuro-Radiologie, SFNR) and the French Study Group on Haemostasis and Thrombosis (Groupe Français d'Études sur l'Hémostase et la Thrombose, GFHT) was convened, under the supervision of two expert coordinators from the SFAR and the ANARLF. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guideline elaboration process was conducted independently of any industry funding. The authors were required to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of quality of evidence. METHODS: Four fields were defined prior to the literature search: (1) Peri-procedural management, (2) Prevention and management of secondary brain injuries, (3) Management of antiplatelet and anticoagulant treatments, (4) Post-procedural management and orientation of the patient. Questions were formulated using the PICO format (Population, Intervention, Comparison, and Outcomes) and updated as needed. Analysis of the literature was then conducted and the recommendations were formulated according to the GRADE methodology. RESULTS: The SFAR/ANARLF/SFNV/SFNR/GFHT guideline panel drew up 18 recommendations regarding anaesthetic management of mechanical thrombectomy procedures. Due to a lack of data in the literature allowing to conclude with high certainty on relevant clinical outcomes, the experts decided to formulate these guidelines as "Professional Practice Recommendations" (PPR) rather than "Formalized Expert Recommendations". After two rounds of rating and several amendments, a strong agreement was reached on 100% of the recommendations. No recommendation could be formulated for two questions. CONCLUSIONS: Strong agreement among experts was reached to provide a sizable number of recommendations aimed at optimising anaesthetic management for thrombectomy in patients suffering from stroke.

Influence of User Posture and Virtual Exercise on Impression of Locomotion During VR Observation.

A seated user watching his avatar walking in Virtual Reality (VR) may have an impression of walking. In this paper, we show that such an impression can be extended to other postures and other locomotion exercises. We present two user studies in which participants wore a VR headset and observed a first-person avatar performing virtual exercises. In the first experiment, the avatar walked and the participants (n=36) tested the simulation in 3 different postures (standing, sitting and Fowler's posture). In the second experiment, other participants (n=18) were sitting and observed the avatar walking, jogging or stepping over virtual obstacles. We evaluated the impression of locomotion by measuring the impression of walking (respectively jogging or stepping) and embodiment in both experiments. The results show that participants had the impression of locomotion in either sitting, standing and Fowler's posture. However, Fowler's posture significantly decreased both the level of embodiment and the impression of locomotion. The sitting posture seems to decrease the sense of agency compared to standing posture. Results also show that the majority of the participants experienced an impression of locomotion during the virtual walking, jogging, and stepping exercises. The embodiment was not influenced by the type of virtual exercise. Overall, our results suggest that an impression of locomotion can be elicited in different users' postures and during different virtual locomotion exercises. They provide valuable insight for numerous VR applications in which the user observes a self-avatar moving, such as video games, gait rehabilitation, training, etc.

Effect of Vibrations on Impression of Walking and Embodiment With First- and Third-Person Avatar.

We investigate how underfoot vibrotactile feedback can be used to increase the impression of walking and embodiment of static users represented by a first- or third-person avatar. We designed a multi-sensory setup involving avatar displayed on an HMD, and a set of vibrotactile effects displayed at every footstep. In a first study (N = 44), we compared the impression of walking in 3 vibrotactile conditions : 1) with a "constant" vibrotactile rendering reproducing simple contact information, 2) with a more sophisticated "phase-based" vibrotactile rendering the successive contacts of a walking cycle and 3) without vibrotactile feedback. The results show that overall both constant and phase-based rendering significantly improve the impression of walking in first and third-person perspective. Interestingly, the more realistic phase-based rendering seems to increase significantly the impression of walking in the third-person condition, but not in the first-person condition. In a second study (N=28), we evaluated the embodiment towards first- and third-person avatar while receiving no vibrotactile feedback or by receiving vibrotactile feedback. The results show that vibrotactile feedback improves embodiment in both perspectives of the avatar. Taken together, our results support the use of vibrotactile feedback when users observe first- and third-person avatar. They also suggest that constant and phase-based rendering could be used with first-person avatar and support the use of phase-based rendering with third-person avatar. They provide valuable insight for stimulations in any VR applications in which the impression of walking is prominent such as for virtual visits, walking rehabilitation, video games, etc.

Guidelines for the management of patients with severe acute pancreatitis, 2021.

OBJECTIVE: To provide guidelines for the management of the intensive care patient with severe acute pancreatitis. DESIGN: A consensus committee of 22 experts was convened. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guideline construction process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The most recent SFAR and SNFGE guidelines on the management of the patient with severe pancreatitis were published in 2001. The literature now is sufficient for an update. The committee studied 14 questions within 3 fields. Each question was formulated in a PICO (Patients Intervention Comparison Outcome) format and the relevant evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. RESULTS: The experts' synthesis work and their application of the GRADE® method resulted in 24 recommendations. Among the formalised recommendations, 8 have high levels of evidence (GRADE 1+/-) and 12 have moderate levels of evidence (GRADE 2+/-). For 4 recommendations, the GRADE method could not be applied, resulting in expert opinions. Four questions did not find any response in the literature. After one round of scoring, strong agreement was reached for all the recommendations. CONCLUSIONS: There was strong agreement among experts for 24 recommendations to improve practices for the management of intensive care patients with severe acute pancreatitis.

Clinical Benefit of Extubation in Patients on Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Although patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock are usually supported with mechanical ventilation, it is not clear whether sedation cessation and extubation might improve outcomes. DESIGN: Retrospective cohort study with propensity score overlap weighting analysis. SETTING: Three ICUs in a 1,500-bed tertiary university hospital. PATIENTS: From an overall cohort of 641 patients with venoarterial-extracorporeal membrane oxygenation support, the primary analysis was performed in 344 patients who had been successfully decannulated in order to reduce immortal time bias. MEASUREMENTS AND MAIN RESULTS: Seventy-five patients (22%) were extubated during extracorporeal membrane oxygenation support and were subsequently decannulated alive. Forty-nine percent received noninvasive ventilation, and 25% had emergency reintubation for respiratory, neurologic, or hemodynamic reasons. Higher Simplified Acute Physiology Score II at admission (odds ratio, 0.97; 95% CI [0.95-0.99]; p = 0.008) was associated with a lower probability of extubation, whereas cannulation in cardiac surgery ICU (odds ratio, 3.14; 95% CI [1.21-8.14]; p = 0.018) was associated with an increased probability. Baseline characteristics were well balanced after propensity score overlap weighting. The number of ICU-free days within 30 days of extracorporeal membrane oxygenation decannulation was significantly higher among extubated patients compared with nonextubated patients (22 d [11-26 d] vs 18 d [7-25 d], respectively; p = 0.036). There were no differences in other outcomes including ventilator-associated pneumonia (odds ratio, 0.96; 95% CI [0.51-1.82]; p = 0.90) and all-cause mortality within 30 days of extracorporeal membrane oxygenation decannulation (5% vs 17%; hazard ratio, 0.54; 95% CI [0.19-1.59]; p = 0.27).As a secondary analysis, outcomes were compared in the overall cohort of 641 venoarterial extracorporeal membrane oxygenation-supported patients. Results were consistent with the primary analysis as extubated patients had a higher number of ICU-free days (18 d [0-24 d] vs 0 d [0-18 d], respectively; < 0.001) and a lower risk of death within 30 days of extracorporeal membrane oxygenation cannulation (hazard ratio, 0.45; 95% CI [0.29-0.71]; p = 0.001). CONCLUSIONS: Extubation during venoarterial-extracorporeal membrane oxygenation support is safe, feasible, and associated with greater ICU-free days.

Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan-Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients' prognosis emphasize the need for a better awareness in these particular populations.

Epinephrine administration in venoarterial extracorporeal membrane oxygenation patients is associated with mortality: a retrospective cohort study.

AIMS: Knowledge about the impact of epinephrine on the outcome in venoarterial (VA) extracorporeal membrane oxygenation (ECMO) patients is limited, and existing data are conflicting. METHODS AND RESULTS: We conducted a retrospective cohort study in a 1500 bed tertiary university hospital. Five hundred and eighty-nine VA-ECMO patients were analysed. The median age was 57 years [47-65], 68% of male. The major indications for ECMO were post-cardiotomy cardiogenic shock (CS) (38%) and medical CS (36%). Two hundred and sixty-two (44.5%) patients received epinephrine alone or associated with another catecholamine while on ECMO. Baseline factors significantly associated with epinephrine administration were younger age, higher sequential organ failure assessment score, cardiac arrest at implantation, and intra-aortic balloon pump support at implantation, whereas medical CS and dobutamine administration were significantly associated with a lower risk of epinephrine administration. Epinephrine administration was independently associated with death [hazard ratio = 1.68 (1.44-2.23); P < 0.01]. A sensitivity analysis with propensity score inverse probability weighting in complete cases confirmed a significant association of epinephrine administration with death [hazard ratio = 1.69 (1.43-2.00); P < 0.001]. CONCLUSIONS: Among patients who required VA-ECMO, epinephrine administration was associated with an increased risk for death.