Annals of Intensive Care最新文献

Background: Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP.

Methods: We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality.

Results: Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97).

Conclusion: In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes.

Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239.

Clinicaltrials: gov NCT04558476. Registered 2020-09-11, https://www.

Clinicaltrials: gov/study/NCT04558476 .

Background: Acute exacerbations of COPD (AECOPD) are common and significantly contribute to mortality in patients with COPD. Prognostic scores can assist clinicians in making tailored decisions to manage AECOPD. In the current study, we therefore aimed to evaluate the performance of the Noninvasive Ventilation Outcomes (NIVO) score, originally designed to assess in-ICU mortality, in predicting 1 year mortality and NIV failure in AECOPD.

Methods: This retrospective study analyzed data from patients hospitalized for AECOPD requiring mechanical ventilation between January 1st, 2018, and December 31st, 2022. Mortality was assessed at the end of ICU stay and 1 year after admission, while NIV failure was defined as intubation or death without intubation.

Results: Among 302 ICU admissions of COPD patients, 190 patients with AECOPD requiring mechanical ventilation were included. Of these, 44 (23%) died in the ICU, 62 out of 184 (34%) failed NIV, and 78 (41%) died within 1 year of admission. Patients who died in ICU or experienced NIV failure had more severe COPD and more impaired blood gas parameters at admission. The NIVO score demonstrated an AUC of 0.68 in predicting 1-year mortality and an AUC of 0.85 in predicting NIV failure. A NIVO score over 7 was associated with higher 1-year mortality and NIV failure (HR of 4.4 [1.8-10.9] and 41.6 [5.6-307.9], respectively).

Conclusion: Beyond predicting in-ICU mortality, the NIVO-score is a reliable tool in predicting 1-year mortality and NIV failure in AECOPD.

Background: This narrative review was written by an expert panel to the members of the jury to help in the development of clinical practice guidelines on oxygen therapy.

Results: According to the expert panel, acute hypoxemic respiratory failure was defined as PaO₂ < 60 mm Hg or SpO₂ < 90% on room air, or PaO₂/FiO₂ ≤ 300 mm Hg. Supplemental oxygen should be administered according to the monitoring of SpO₂, with the aim at maintaining SpO₂ above 92% and below 98%. Noninvasive respiratory supports are generally reserved for the most hypoxemic patients with the aim of relieving dyspnea. High-flow nasal cannula oxygen (HFNC) seems superior to conventional oxygen therapy (COT) as a means of avoiding intubation and may therefore be should probably be used as a first-line noninvasive respiratory support in patients requiring more than 6 L/min of oxygen or PaO₂/FiO₂ ≤ 200 mm Hg and a respiratory rate above 25 breaths/minute or clinical signs of respiratory distress, but with no benefits on mortality. Continuous positive airway pressure (CPAP) cannot currently be recommended as a first-line noninvasive respiratory support, since its beneficial effects on intubation remain uncertain. Despite older studies favoring noninvasive ventilation (NIV) over COT, recent clinical trials fail to show beneficial effects with NIV compared to HFNC. Therefore, there is no evidence to support the use of NIV or CPAP as first-line treatment if HFNC is available. Clinical trials do not support the hypothesis that noninvasive respiratory supports may lead to late intubation. The potential benefits of awake prone positioning on the risk of intubation in patients with COVID-19 cannot be extrapolated to patients with another etiology.

Conclusions: Whereas oxygen supplementation should be initiated for patients with acute hypoxemic respiratory failure defined as PaO₂ below 60 mm Hg or SpO₂ < 90% on room air, HFNC should be the first-line noninvasive respiratory support in patients with PaO₂/FiO₂ ≤ 200 mm Hg with increased respiratory rate. Further studies are needed to assess the potential benefits of CPAP, NIV through a helmet and awake prone position in patients with acute hypoxemic respiratory failure not related to COVID-19.

In cardiogenic shock, biomarkers should ideally help make the diagnosis, choose the right therapeutic options and monitor the patient in addition to clinical and echocardiographic indices. Among "old" biomarkers that have been used for decades, lactate detects, quantifies, and follows anaerobic metabolism, despite its lack of specificity. Renal and liver biomarkers are indispensable for detecting the effect of shock on organ function and are highly predictive of poor outcomes. Direct biomarkers of cardiac damage such as cardiac troponins, B-type natriuretic and N-terminal pro-B-type natriuretic peptides have a good prognostic value, but they lack specificity to detect a cardiogenic cause of shock, as many factors influence their plasma concentrations in critically ill patients. Among the biomarkers that have been more recently described, dipeptidyl peptidase-3 is one of the most interesting. In addition to its prognostic value, it could represent a therapeutic target in cardiogenic shock in the future as a specific antibody inhibits its activity. Adrenomedullin is a small peptide hormone secreted by various tissues, including vascular smooth muscle cells and endothelium, particularly under pathological conditions. It has a vasodilator effect and has prognostic value during cardiogenic shock. An antibody inhibits its activity and so adrenomedullin could represent a therapeutic target in cardiogenic shock. An increasing number of inflammatory biomarkers are also of proven prognostic value in cardiogenic shock, reflecting the inflammatory reaction associated with the syndrome. Some of them are combined to form prognostic proteomic scores. Alongside clinical variables, biomarkers can be used to establish biological "signatures" characteristic of the pathophysiological pathways involved in cardiogenic shock. This helps describe patient subphenotypes, which could in the future be used in clinical trials to define patient populations responding specifically to a treatment.

Background: Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2).

Results: Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77-0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85-0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82-0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05).

Conclusions: As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI.

Trial registration: Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1 .

Background: Bleeding events are common complications in critically ill patients with haematological malignancies. The objective of this study was to assess the incidence and identify determinants of ICU-acquired severe bleeding events in critically ill patients with haematological malignancies. We conducted a single-center retrospective study including all adult patients with a history of haematological malignancy requiring unplanned ICU admission over a 12-year period (2007-2018). The primary endpoint was the occurrence of ICU-acquired (i.e. after the first 24 h in the ICU) severe bleeding events, as defined as grades 3 or 4 of the World Health Organization classification.

Results: A total of 1012 patients were analysed, mainly with a diagnosis of lymphoma (n = 434, 42.9%) and leukaemia or myelodysplastic syndrome (n = 266, 26.3%). Most patients were recently diagnosed (n = 340, 33.6%) and under active cancer treatment within the last 3 months (n = 604, 59.7%). The main cause for admission was infection (n = 479, 47.3%), but a significant proportion of patients were admitted for a primary haemorrhage (n = 99, 10%). ICU-acquired severe bleeding events occurred in 109 (10.8%) patients after 3.0 days [1.0-7.0] in the ICU. The main source of bleeding was the gastrointestinal tract (n = 44, 40.3%). Patients experiencing an ICU-acquired severe bleeding event displayed prolonged in-ICU length of stay (9.0 days [1.0-6.0] vs. 3.0 [3.5-15.0] in non-bleeding patients, p < 0.001) and worsened outcomes with increased in-ICU and in-hospital mortality rates (55% vs. 18.3% and 65.7% vs. 33.1%, respectively, p < 0.001). In multivariate analysis, independent predictors of ICU-acquired severe bleeding events were chronic kidney disease (cause-specific hazard 2.00 [1.19-3.31], p = 0.008), a primary bleeding event present at the time of ICU admission (CSH 4.17 [2.71-6.43], p < 0.001), non-platelet SOFA score (CSH per point increase 1.06 [1.01-1.11], p = 0.02) and prolonged prothrombin time (CSH per 5-percent increase 0.90 [0.85-0.96], p = 0.001) on the day prior to the event of interest.

Conclusions: Major bleeding events are common complications in critically ill patients with haematological malignancies and are associated with a worsened prognosis. We identified relevant risk factors of bleeding which may prompt closer monitoring or preventive measures.

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.

Background: Sigh breaths may impact outcomes in acute hypoxemic respiratory failure (AHRF) during assisted mechanical ventilation. We investigated whether sigh breaths may impact mortality in predefined subgroups of patients enrolled in the PROTECTION multicenter clinical trial according to: 1.the physiological response in oxygenation to Sigh (responders versus non-responders) and 2.the set levels of positive end-expiratory pressure (PEEP) (High vs. Low-PEEP). If mortality differed between Sigh and No Sigh, we explored physiological daily differences at 7-days.

Results: Patients were randomized to pressure support ventilation (PSV) with Sigh (Sigh group) versus PSV with no sigh (No Sigh group). (1) Sighs were not associated with differences in 28-day mortality in responders to baseline sigh-test. Contrarily-in non-responders-56 patients were randomized to Sigh (55%) and 28-day mortality was lower with sighs (17%vs.36%, log-rank p = 0.031). (2) In patients with PEEP > 8cmH₂O no difference in mortality was observed with sighs. With Low-PEEP, 54 patients were randomized to Sigh (48%). Mortality at 28-day was reduced in patients randomised to sighs (13%vs.31%, log-rank p = 0.021). These findings were robust to multivariable adjustments. Tidal volume, respiratory rate and ventilatory ratio decreased with Sigh as compared with No Sigh at 7-days. Ventilatory ratio was associated with mortality and successful extubation in both non-responders and Low-PEEP.

Conclusions: Addition of Sigh to PSV could reduce mortality in AHRF non-responder to Sigh and exposed to Low-PEEP. Results in non-responders were not expected. Findings in the low PEEP group may indicate that insufficient PEEP was used or that Low PEEP may be used with Sigh. Sigh may reduce mortality by decreasing physiologic dead space and ventilation intensity and/or optimizing ventilation/perfusion mismatch.

Clinical trial registration: ClinicalTrials.gov; Identifier: NCT03201263.

Background: The transfusion strategy in the acute phase of myocardial infarction (AMI) remains a debated topic with non-standardized guidelines. This study aimed to evaluate the impact of liberal versus restrictive transfusion strategies on mortality during AMI.

Methods: A systematic search was conducted across MEDLINE, EMBASE, and the COCHRANE library databases, focusing on randomized controlled trials (RCTs). The primary endpoint was the latest measured mortality within 90 days following myocardial infarction (MI). Secondary endpoints included recurrence of MI, cardiovascular mortality, stroke occurrence, unplanned revascularization, and a composite endpoint of death or recurrent MI. Mixed and random-effects models were employed to estimate relative risks. Sensitivity analyses were conducted using two approaches: one incorporating only studies assessed as low risk of bias according to the Rob2 tool, and another employing a Bayesian analysis.

Results: Four RCTs including a total of 4324 participants were analyzed. Neither the fixed-effect nor random-effects models demonstrated a significant reduction in mortality, with risk ratios (RR) of 1.16 (95% CI 0.95-1.40) for the fixed-effect model and 1.13 (95% CI 0.67-1.91) for the random-effects model (GRADE: low certainty of evidence). Sensitivity analyses, including the exclusion of two high-risk-of-bias studies and a Bayesian analysis, were consistent with the primary analysis. For the composite outcome death or MI both fixed-effect and random-effects models showed a statistically significant RR of 1.18 (95% CI 1.01-1.37) with negligible heterogeneity (I² = 0%, p = 0.46), indicating results unfavorable to restrictive transfusion (GRADE: very low certainty of evidence). However, this result was primarily driven by a single study. For cardiac mortality, the fixed-effects model indicated a significant RR of 1.42 (95% CI 1.07-1.88), whereas the random-effects model showed non-significant RR of 1.05 (95% CI 0.36-3.80). Analyses of other secondary endpoints did not show statistically significant results.

Conclusions: Our analysis did not demonstrate a significant benefit in early mortality with a liberal transfusion strategy compared to a restrictive strategy for AMI, low certainty of evidence. Liberal transfusion may reduce the risk of the composite outcome death or MI, with very low certainty of evidence. These findings should be interpreted with caution in critically ill patients.

Background: The micro-axial flow pump Impella, a new mechanical circulatory device for cardiogenic shock, is still only available in a limited number of hospitals, due to the facility certification requirements and insufficient evidence of the benefit of introducing Impella in hospitals. This study aimed to evaluate the impact of introducing Impella in hospitals on in-hospital mortality of patients treated with extracorporeal membrane oxygenation (ECMO).

Methods: Using a nationwide Japanese inpatient database, we identified patients who received ECMO during hospitalization between 1 April 2014 and 31 March 2021. A hospital-level propensity score-matched cohort was created matching hospitals that introduced Impella (exposure group) to those that did not introduce Impella (control group). The inclusion period in each hospital was divided into two time periods according to the time of Impella introduction in the exposure group and the corresponding hospital in the control group (before and after exposure). The primary outcome was in-hospital mortality. Uncontrolled and controlled interrupted time-series analyses involved before-after exposure comparison and exposure-control comparison.

Results: Out of 34,379 eligible patients, we created a matched cohort of 8351 patients from 86 hospitals with Impella introduction (exposure group) and 7230 patients from 86 hospitals without Impella introduction (control group). In-hospital mortality before and after exposure was 62.5% and 59.3, respectively, in the exposure group; and 66.8% and 63.7%, respectively, in the control group. Uncontrolled interrupted time-series analysis showed no significant level change or trend change in the before-after exposure comparison in both the exposure and the control groups. Controlled interrupted time-series analysis also showed no significant level change (-0.01%; 95% confidence intervals -5.36% to + 5.33%) or trend change (+ 0.10%, -0.30% to + 0.40%) after exposure in the exposure-control comparison.

Conclusions: This nationwide inpatient database study showed no association between Impella introduction in hospitals and in-hospital mortality of patients who underwent ECMO. Because this study confined itself to analze of the impact of the introduction of Impella solely at the hospital level, further detailed studies are warranted to assess its efficacy at the patient level.