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Background: Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch., Methods: This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support., Results: Eighty patients, with a median [IQR25-75] age of 44 [29-53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3-4.9], p = 0.009)., Conclusions: The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources., (© 2024. The Author(s).)

Background: The optimal timing of weaning from venovenous extracorporeal membrane oxygenation (VV ECMO) and its modalities have been rarely studied., Methods: Retrospective, multicenter cohort study over 7 years in two tertiary ICUs, high-volume ECMO centers in France and Italy. Patients with ARDS on ECMO and successfully weaned from VV ECMO were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning., Results: 292 adult patients with severe ARDS were weaned from controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95% CI], 1.23 [0.84-1.82]). ECMO-related complications were not statistically different between patients receiving these two mechanical ventilation strategies. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy, but not mechanical ventilation modalities during SGOT, were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning., Conclusions: Time to successful weaning from mechanical ventilation within 90 days post-ECMO was not associated with the mechanical ventilation strategy used during SGOT. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation. A national e-survey was conducted among French ICUs in January 2022 to collect data on ICU characteristics, medical staffing, individual physician characteristics, and education and training capacities., Results: Among 290 ICUs contacted, 242 responded (response rate: 83%), representing 4943 ICU beds. The survey revealed an overall of 300 full time equivalent (FTE) ICU physician vacancies in the country. Nearly two-thirds of the participating ICUs reported at least one physician vacancy and 35% relied on traveling physicians to cover shifts. The ICUs most affected by physician vacancies were the ICUs of non-university affiliated public hospitals. The retirements expected in the next five years represented around 10% of the workforce. The median number of physicians per ICU was 7.0, corresponding to a ratio of 0.36 physician (FTE) per ICU bed. In addition, 27% of ICUs were at risk of critical dysfunction or closure due to vacancies and impending retirements., Conclusion: The findings highlight the urgent need to address the shortage of ICU physicians in France. Compared to a similar study conducted in 2012, the inadequacy between ICU physician supply and demand has increased, resulting in a higher number of vacancies. Our study suggests that, among others, increasing the number of ICM residents trained each year could be a crucial step in addressing this issue. Failure to take appropriate measures may lead to further closures of ICUs and increased risks to patients in this healthcare system., (© 2024. The Author(s).)

Objective: To describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence., Methods: Adult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence., Results: Among the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7-13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5-7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8-10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short- and prolonged-antimicrobial treatment., Conclusions: In patients with severe Covid-19-ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration., (© 2024. The Author(s).)

Background: Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS)., Methods: Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results., Results: Forty-seven patients (median age 41 [30-47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients' recovery in only 4% patients., Conclusions: In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Background: Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence., Objectives: To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research., Methods: A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus., Results: We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings., Conclusions: We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios., (© 2023. The Author(s).)

Antibiotic resistance is a major health problem and will be probably one of the leading causes of deaths in the coming years. One of the most effective ways to fight against resistance is to decrease antibiotic consumption. Intensive care units (ICUs) are places where antibiotics are widely prescribed, and where multidrug-resistant pathogens are frequently encountered. However, ICU physicians may have opportunities to decrease antibiotics consumption and to apply antimicrobial stewardship programs. The main measures that may be implemented include refraining from immediate prescription of antibiotics when infection is suspected (except in patients with shock, where immediate administration of antibiotics is essential); limiting empiric broad-spectrum antibiotics (including anti-MRSA antibiotics) in patients without risk factors for multidrug-resistant pathogens; switching to monotherapy instead of combination therapy and narrowing spectrum when culture and susceptibility tests results are available; limiting the use of carbapenems to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and new beta-lactams to difficult-to-treat pathogen (when these news beta-lactams are the only available option); and shortening the duration of antimicrobial treatment, the use of procalcitonin being one tool to attain this goal. Antimicrobial stewardship programs should combine these measures rather than applying a single one. ICUs and ICU physicians should be at the frontline for developing antimicrobial stewardship programs., (© 2023. The Author(s).)

Background: Acute distress respiratory syndrome (ARDS) patients with veno-venous extra corporeal membrane oxygenation (ECMO) support are particularly exposed to ECMO-associated infection (ECMO-AI). Unfortunately, data regarding AI prophylaxis in this setting are lacking. Selective decontamination regimens decrease AI incidence, including ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in critically ill patients. We hypothesized that a multiple-site decontamination (MSD) regimen is associated with a reduction in the incidence of AI among VV-ECMO patients., Methods: We conducted a retrospective observational study in three French ECMO referral centers from January 2010 to December 2021. All adult patients (> 18 years old) who received VV-ECMO support for ARDS were eligible. In addition to standard care (SC), 2 ICUs used MSD, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, once daily chlorhexidine body-wash and a 5-day nasal mupirocin course. AIs were compared between the 2 ICUs using MSD (MSD group) and the last ICU using SC., Results: They were 241 patients available for the study. Sixty-nine were admitted in an ICU that applied MSD while the 172 others received standard care and constituted the SC group. There were 19 ECMO-AIs (12 VAP, 7 BSI) in the MSD group (1162 ECMO-days) compared to 143 AIs (104 VAP, 39 BSI) in the SC group (2376 ECMO-days), (p < 0.05 for all infection site). In a Poisson regression model, MSD was independently associated with a lower incidence of ECMO-AI (IRR = 0.42, 95% CI [0.23-0.60] p < 0.001). There were 30 multidrug resistant microorganisms (MDRO) acquisition in the SC group as compared with two in the MSD group (IRR = 0.13, 95% CI [0.03-0.56] p = 0.001). Mortality in ICU was similar in both groups (43% in the SC group vs 45% in the MSD group p = 0.90). Results were similar after propensity-score matching., Conclusion: In this cohort of patients from different hospitals, MSD appeared to be safe in ECMO patients and may be associated with improved outcomes including lower ECMO-AI and MDRO acquisition incidences. Since residual confounders may persist, these promising results deserve confirmation by randomized controlled trials., (© 2023. The Author(s).)

Background: Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs., Results: We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO 2 (100% (70-100) vs. 90% (60-100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04-1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12-1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1-3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38-1.26], p = 0.23)., Conclusions: In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality., (© 2022. The Author(s).)

Background: Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis., Methods: We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria., Results: Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70-0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50-86], specificity of 85% [55-98], a negative predictive value of 58% [36-93] and a positive predictive value 90% [67-96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12-0.75], p = 0.01)., Conclusion: In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI., (© 2022. The Author(s).)

Background: Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known., Methods: Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation., Results: Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped., Conclusions: HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients., (© 2022. The Author(s).)

Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients., Patients and Methods: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching., Results: Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05-1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population., Conclusion: COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate., (© 2021. The Author(s).)

Rationale: Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion., Methods: A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv., Results: During the study period, 121 patients [62 (50-75) years; 62% male; median SAPSII and SOFA scores 39 (27-52) and 6 (4-8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n  = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n  = 47, 39%), whereas the main non-immune cause was pulmonary infection (n  = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p  = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p  = 0.053). Among patients with a known Svv (n  = 70), immunosuppression [OR 9.41 (1.52-58.3); p  = 0.016], and a low vasculitis activity score [0.84 (0.77-0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure., Conclusions: An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies., (© 2021. The Author(s).)

Introduction: To describe the reasons for intensive care unit (ICU) admission and to evaluate the outcomes and prognostic factors of patients with primary central nervous system lymphoma (PCNSL) admitted to the ICU., Patients and Methods: Retrospective observational cohort study of 101 PCNSL patients admitted to 3 ICUs over a two-decade period., Results: Acute respiratory failure, mainly secondary to aspiration pneumonia and Pneumocystis jirovecii pneumonia, was the leading reason for ICU admission (33%). Aspiration pneumonia was more common in patients with brainstem tumor (67% vs. 0%, p < 0.001), whereas patients with intracranial hypertension were more frequently admitted for coma without seizures (61% vs. 9%, p = 0.004). Hospital and 6-month mortality were 47% and 53%, respectively. In multivariate analysis, admission for coma without seizures (OR 7.28), cancer progression (OR 3.47), mechanical ventilation (OR 6.58) and vasopressors (OR 4.07) were associated with higher 6-month mortality. Karnofsky performance status prior to ICU admission was independently associated with lower 6-month mortality (OR 0.96)., Discussion: Six-month survival of PCNSL patients admitted to the ICU appears to be relatively favorable (around 50%) and the presence of PCNSL alone is not a relevant criterion for ICU refusal. Predictive factors of mortality may help clinicians to make optimal triage decisions.

Background: The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation., Methods: This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37)., Results: The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0-51] and 0 [0-43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups., Conclusions: In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

Background: Systemic rheumatic diseases (SRDs) are a group of inflammatory disorders that can require intensive care unit (ICU) admission because of multiorgan involvement with end-organ failure(s). Critically ill SRD patients requiring extracorporeal membrane oxygenation (ECMO) were studied to gain insight into their characteristics and outcomes., Methods: This French monocenter, retrospective study included all SRD patients requiring venovenous (VV)- or venoarterial (VA)-ECMO admitted to a 26-bed ECMO-dedicated ICU from January 2006 to February 2020. The primary endpoint was in-hospital mortality., Results: Ninety patients (male/female ratio: 0.5; mean age at admission: 41.6 ± 15.2 years) admitted to the ICU received VA/VV-ECMO, respectively, for an SRD-related flare (n = 69, n = 38/31) or infection (n = 21, n = 10/11). SRD was diagnosed in-ICU for 31 (34.4%) patients. In-ICU and in-hospital mortality rates were 48.9 and 51.1%, respectively. Nine patients were bridged to cardiac (n = 5) or lung transplantation (n = 4), or left ventricular assist device (n = 2). The Cox multivariable model retained the following independent predictors of in-hospital mortality: in-ICU SRD diagnosis, day-0 Simplified Acute Physiology Score (SAPS) II score ≥ 70 and arterial lactate ≥ 7.5 mmol/L for VA-ECMO-treated patients; diagnosis other than vasculitis, day-0 SAPS II score ≥ 70, ventilator-associated pneumonia and arterial lactate ≥ 7.5 mmol/L for VV-ECMO-treated patients., Conclusions: ECMO support is a relevant rescue technique for critically ill SRD patients, with 49% survival at hospital discharge. Vasculitis was independently associated with favorable outcomes of VV-ECMO-treated patients. Further studies are needed to specify the role of ECMO for SRD patients.

Background: The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons., Results: Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42-56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8-16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups., Conclusions: Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.

Background: Prone positioning (PP) during veno-venous ECMO is feasible, but its physiological effects have never been thoroughly evaluated. Our objectives were to describe, through electrical impedance tomography (EIT), the impact of PP on global and regional ventilation, and optimal PEEP level., Methods: A monocentric study conducted on ECMO-supported severe ARDS patients, ventilated in pressure-controlled mode, with 14-cmH 2 O driving pressure and EIT-based "optimal PEEP". Before, during and after a 16-h PP session, EIT-based distribution and variation of tidal impedance, VT dorsal /VT global ratio, end-expiratory lung impedance (EELI) and static compliance were collected. Subgroup analyses were performed in patients who increased their static compliance by ≥ 3 mL/cmH 2 O after 16 h of PP., Results: For all patients (n = 21), tidal volume and EELI were redistributed from ventral to dorsal regions during PP. EIT-based optimal PEEP was significantly lower in PP than in supine position. Median (IQR) optimal PEEP decreased from 14 (12-16) to 10 (8-14) cmH 2 O. Thirteen (62%) patients increased their static compliance by ≥ 3 mL/cmH 2 O after PP on ECMO. This subgroup had higher body mass index, more frequent viral pneumonia, shorter ECMO duration, and lower baseline VT dorsal /VT global ratio than patients with compliance ≤ 3 mL/cmH 2 O (P < 0.01)., Conclusion: Although baseline tidal volume distribution on EIT may predict static compliance improvement after PP on ECMO, our results support physiological benefits of PP in all ECMO patients, by modifying lung mechanics and potentially reducing VILI. Further studies, including a randomized-controlled trial, are now warranted to confirm potential PP benefits during ECMO.

Background: Structural neurological complications (ischemic stroke and intracranial bleeding) and their risk factors in patients receiving venoarterial-extracorporeal membrane oxygenation (VA-ECMO) are poorly described. Our objective was to describe frequencies, outcomes and risk factors for neurological complications (ischemic stroke and intracranial bleeding) in patients receiving VA-ECMO., Methods: Retrospective observational study conducted, from 2006 to 2014, in a tertiary referral center on patients who developed a neurological complication(s) on VA-ECMO., Results: Among 878 VA-ECMO-treated patients, 65 (7.4%) developed an ECMO-related brain injury: 42 (5.3%) ischemic strokes and 20 (2.8%) intracranial bleeding, occurring after a median [25th;75th percentile] of 11 [6;18] and 5 [2;9] days of support, respectively. Intracranial bleeding but not ischemic stroke was associated with higher mortality. Multivariable analysis retained only platelet level > 350 giga/L as being associated with ischemic stroke. Female sex, central VA-ECMO and platelets < 100 giga/L at ECMO start were independently associated with intracranial bleeding with respective odds ratios [95% CI] of 2.9 [1.1-7.5], 3.8 [1.1-10.2] and 3.7 [1.4-9.7]. In a nested case-control study, rapid CO 2 -level change from before-to-after ECMO start also seemed to be associated with intracranial bleeding., Conclusions: Neurological events are frequent in VA-ECMO-treated patients. Ischemic stroke is the most frequent, occurs after 1 week on ECMO support, has no specific risk factor and is not associated with higher mortality. Intracranial bleeding occurs earlier and is associated with female sex, central VA-ECMO, low platelet count and rapid CO 2 change at ECMO start, and high mortality., Level of Evidence: This study provides Class IV evidence that central VA-ECMO, low platelet count and rapid CO 2 change at ECMO start are associated with intracranial bleeding and high mortality.

Background: The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists., Results: The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases., Conclusions: HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

Tracheotomy is widely used in intensive care units, albeit with great disparities between medical teams in terms of frequency and modality. Indications and techniques are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of tracheotomy in adult critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de Réanimation de Langue Française) and the French Society of Anesthesia and Intensive Care Medicine (Société Francaise d'Anesthésie Réanimation) with the participation of the French Emergency Medicine Association (Société Française de Médecine d'Urgence), the French Society of Otorhinolaryngology. Sixteen experts and two coordinators agreed to consider questions concerning tracheotomy and its practical implementation. Five topics were defined: indications and contraindications for tracheotomy in intensive care, tracheotomy techniques in intensive care, modalities of tracheotomy in intensive care, management of patients undergoing tracheotomy in intensive care, and decannulation in intensive care. The summary made by the experts and the application of GRADE methodology led to the drawing up of 8 formal guidelines, 10 recommendations, and 3 treatment protocols. Among the 8 formal guidelines, 2 have a high level of proof (Grade 1+/-) and 6 a low level of proof (Grade 2+/-). For the 10 recommendations, GRADE methodology was not applicable and instead 10 expert opinions were produced.

Background: Pheochromocytoma, a rare catecholamine-producing tumor, might provoke stress-induced Takotsubo-like cardiomyopathy and severe cardiogenic shock. Because venoarterial-extracorporeal membrane oxygenation (VA-ECMO) rescue of pheochromocytoma-induced refractory cardiogenic shock has rarely been reported, we reviewed our ICU patients' presentations and outcomes., Methods: All pheochromocytoma-induced refractory cardiogenic shock cases managed with VA-ECMO (January 2007-March 2015) were prospectively included and reviewed. We also performed a systematic review on this topic., Results: Nine patients (7 women, 2 men; 31-51 [median, 43 (IQR 36-49) years old]) were included; none had a previously known pheochromocytoma. Six of them had medical histories suggestive of the diagnosis: palpitations and headaches for several months for four, multiple endocrine neoplasia syndrome type 1 for one and recurrent Takotsubo disease for one; at hospital admission, all were hypertensive despite cardiogenic shock. Three others had an identified surgical triggering factor. All nine patients rapidly developed refractory cardiogenic shock with very severe left ventricular (LV) impairment (LV ejection-fraction range 5-20%; LV outflow-tract velocity-time integral range 3-8 cm). Seven patients' abdominal computed tomography scans showed pheochromocytoma-suggestive adrenal gland tumors (no scan during ICU stay for 2). Despite VA-ECMO implantation, three patients died of refractory multiple organ failure. For the six others, myocardial function improved and ECMO was removed 3-7 days post-implantation; α- and β-blockers were progressively introduced. Five survivors underwent pheochromocytoma excision 3 weeks-4 months post-ICU discharge, with satisfactory outcomes. One patient, whose pheochromocytoma was diagnosed 1 year after the index event, underwent uneventful surgical adrenalectomy. Systematic review retrieved 40 cases of pheochromocytoma-induced cardiogenic shock requiring mechanical support (mostly ECMO), with a mortality rate of 7%. Pheochromocytoma was removed surgically after mechanical support weaning in 31 patients and during mechanical support in 5. Four were not operated., Conclusions: Pheochromocytoma is a rare but reversible cause of cardiogenic shock amenable to VA-ECMO rescue. Adrenal gland imaging should be obtained for all patients with unexplained cardiogenic shock. Lastly, it might be safer to perform adrenalectomy several weeks after the initial catastrophic presentation, once recovery of LV systolic function is complete.

Gram-negative pneumonia in patients who are intubated and mechanically ventilated is associated with increased morbidity and mortality as well as higher healthcare costs compared with those who do not have the disease. Intravenous antibiotics are currently the standard of care for pneumonia; however, increasing rates of multidrug resistance and limited penetration of some classes of antimicrobials into the lungs reduce the effectiveness of this treatment option, and current clinical cure rates are variable, while recurrence rates remain high. Inhaled antibiotics may have the potential to improve outcomes in this patient population, but their use is currently restricted by a lack of specifically formulated solutions for inhalation and a limited number of devices designed for the nebulization of antibiotics. In this article, we review the challenges clinicians face in the treatment of pneumonia and discuss the characteristics that would constitute an ideal inhaled drug/device combination. We also review inhaled antibiotic options currently in development for the treatment of pneumonia in patients who are intubated and mechanically ventilated.

In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics.

Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (<0.25 ng/mL); in patients having nosocomial LRTI, data are insufficient to recommend initiating therapy based on a single PCT level or even repeated measurements. For children with suspected bacterial meningitis, we recommend using a decision rule as an aid to therapeutic decisions, such as the Bacterial Meningitis Score or the Meningitest®; a single PCT level ≥0.5 ng/mL also may be used, but false-negatives may occur. In adults with suspected bacterial meningitis, we suggest integrating serum PCT measurements in a clinical decision rule to help distinguish between viral and bacterial meningitis, using a 0.5 ng/mL threshold. For ICU patients suspected of community-acquired infection, we do not recommend using a threshold serum PCT value to help the decision to initiate antibiotic therapy; data are insufficient to recommend using PCT serum kinetics for the decision to initiate antibiotic therapy in patients suspected of ICU-acquired infection. In children, CRP can probably be used to help discontinue therapy, although the evidence is limited. In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has been obtained. For ICU patients who have nonbacteremic sepsis from a known site of infection, antibiotics can be stopped if the PCT level at day 3 is < 0.5 ng/mL or has decreased by >80% relative to the highest level recorded, irrespective of the severity of the infectious episode; in bacteremic patients, a minimal duration of therapy of 5 days is recommended.