Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

Management of cardiogenic shock: a narrative review.

Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population.

How to use echocardiography to manage patients with shock?

Echocardiography enables the intensivist to assess the patient with circulatory failure. It allows the clinician to identify rapidly the type and the cause of shock in order to develop an effective management strategy. Important characteristics in the setting of shock are that it is non-invasive and can be rapidly applied. Early and repeated echocardiography is a valuable tool for the management of shock in the intensive care unit. Competency in basic critical care echocardiography is now regarded as a mandatory part of critical care training with clear guidelines available. The majority of pathologies found in shocked patients are readily identified using basic level 2D and M-mode echocardiography. The four core types of shock (cardiogenic, hypovolemic, obstructive, and septic) can readily be identified by echocardiography. Echocardiography can differentiate the different pathologies that may be the cause of each type of shock. More importantly, as a result of more complex and elderly patients, the shock may be multifactorial, such as a combination of cardiogenic and septic shock, which emphasises on the added value of transthoracic echocardiography (TTE) in such population of patients. In this review we aimed to provide to clinicians a bedside strategy of the use of TTE parameters to manage patients with shock. In the first part of this overview, we detailed the different TTE parameters and how to use them to identify the type of shock. And in the second part, we focused on the use of these parameters to evaluate the effect of treatments, in different types of shock.

Cardio-respiratory interactions in acute asthma.

Asthma encompasses of respiratory symptoms that occur intermittently and with varying intensity accompanied by reversible expiratory airflow limitation. In acute exacerbations, it can be life-threatening due to its impact on ventilatory mechanics. Moreover, asthma has significant effects on the cardiovascular system, primarily through heart-lung interaction-based mechanisms. Dynamic hyperinflation and increased work of breathing caused by a sharp drop in pleural pressure, can affect cardiac function and cardiac output through different mechanisms. These mechanisms include an abrupt increase in venous return, elevated right ventricular afterload and interdependence between the left and right ventricle. Additionally, Pulsus paradoxus, which reflects the maximum consequences of this heart lung interaction when intrathoracic pressure swings are exaggerated, may serve as a convenient bedside tool to assess the severity of acute asthma acute exacerbation and its response to therapy.

The Eight Unanswered and Answered Questions about the Use of Vasopressors in Septic Shock.

Septic shock is mainly characterized-in addition to hypovolemia-by vasoplegia as a consequence of a release of inflammatory mediators. Systemic vasodilatation due to depressed vascular tone results in arterial hypotension, which induces or worsens organ hypoperfusion. Accordingly, vasopressor therapy is mandatory to correct hypotension and to reverse organ perfusion due to hypotension. Currently, two vasopressors are recommended to be used, norepinephrine and vasopressin. Norepinephrine, an α1-agonist agent, is the first-line vasopressor. Vasopressin is suggested to be added to norepinephrine in cases of inadequate mean arterial pressure instead of escalating the doses of norepinephrine. However, some questions about the bedside use of these vasopressors remain. Some of these questions have been well answered, some of them not clearly addressed, and some others not yet answered. Regarding norepinephrine, we firstly reviewed the arguments in favor of the choice of norepinephrine as a first-line vasopressor. Secondly, we detailed the arguments found in the recent literature in favor of an early introduction of norepinephrine. Thirdly, we reviewed the literature referring to the issue of titrating the doses of norepinephrine using an individualized resuscitation target, and finally, we addressed the issue of escalation of doses in case of refractory shock, a remaining unanswered question. For vasopressin, we reviewed the rationale for adding vasopressin to norepinephrine. Then, we discussed the optimal time for vasopressin administration. Subsequently, we addressed the issue of the optimal vasopressin dose, and finally we discussed the best strategy to wean these two vasopressors when combined.

The place of new antibiotics for Gram-negative bacterial infections in intensive care: report of a consensus conference.

INTRODUCTION: New beta-lactams, associated or not with beta-lactamase inhibitors (NBs/BIs), can respond to the spread of carbapenemase-producing enterobacteriales and nonfermenting carbapenem-resistant bacteria. The risk of emergence of resistance to these NBs/BIs makes guidelines necessary. The SRLF organized a consensus conference in December 2022. METHODS: An ad hoc committee without any conflict of interest (CoI) with the subject identified the molecules (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam and cefiderocol); defined 6 generic questions; drew up a list of subquestions according to the population, intervention, comparison and outcomes (PICO) model; and reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Seven experts in the field proposed their own answers to the questions in a public session and answered questions from the jury (a panel of 10 critical-care physicians without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Due to the frequent lack of powerful studies that have used clinically important criteria of judgment, the recommendations were formulated as expert opinions as often as necessary. RESULTS: The jury provided 17 statements answering 6 questions: (1) Is there a place in the ICU for the probabilistic use of new NBs/IBs active against Gram-negative bacteria? (2) In the context of documented infections with sensitivity to several of these molecules, are there pharmacokinetic, pharmacodynamic, ecological or medico-economic elements for prioritization? (3) What are the possible combinations with these molecules and in what context? (4) Should we integrate these new molecules into a carbapenem-sparing strategy? (5) What pharmacokinetic and pharmacodynamic data are available to optimize their mode of administration in critically ill patients? (6) What are the dosage adaptations in cases of renal insufficiency, hepatocellular insufficiency or obesity? CONCLUSION: These recommendations should optimize the use of NBs/BIs in ICU patients.

Hemodynamic monitoring in cardiogenic shock.

Cardiogenic shock (CS) is a life-threatening condition characterized by acute end-organ hypoperfusion due to inadequate cardiac output that can result in multiorgan failure, which may lead to death. The diminished cardiac output in CS leads to systemic hypoperfusion and maladaptive cycles of ischemia, inflammation, vasoconstriction, and volume overload. Obviously, the optimal management of CS needs to be readjusted in view of the predominant dysfunction, which may be guided by hemodynamic monitoring. Hemodynamic monitoring enables (1) characterization of the type of cardiac dysfunction and the degree of its severity, (2) very early detection of associated vasoplegia, (3) detection and monitoring of organ dysfunction and tissue oxygenation, and (4) guidance of the introduction and optimization of inotropes and vasopressors as well as the timing of mechanical support. It is now well documented that early recognition, classification, and precise phenotyping via early hemodynamic monitoring (e.g., echocardiography, invasive arterial pressure, and the evaluation of organ dysfunction and parameters derived from central venous catheterization) improve patient outcomes. In more severe disease, advanced hemodynamic monitoring with pulmonary artery catheterization and the use of transpulmonary thermodilution devices is useful to facilitate the right timing of the indication, weaning from mechanical cardiac support, and guidance on inotropic treatments, thus helping to reduce mortality. In this review, we detail the different parameters relevant to each monitoring approach and the way they can be used to support optimal management of these patients.

Pathophysiology of fluid administration in critically ill patients.

Fluid administration is a cornerstone of treatment of critically ill patients. The aim of this review is to reappraise the pathophysiology of fluid therapy, considering the mechanisms related to the interplay of flow and pressure variables, the systemic response to the shock syndrome, the effects of different types of fluids administered and the concept of preload dependency responsiveness. In this context, the relationship between preload, stroke volume (SV) and fluid administration is that the volume infused has to be large enough to increase the driving pressure for venous return, and that the resulting increase in end-diastolic volume produces an increase in SV only if both ventricles are operating on the steep part of the curve. As a consequence, fluids should be given as drugs and, accordingly, the dose and the rate of administration impact on the final outcome. Titrating fluid therapy in terms of overall volume infused but also considering the type of fluid used is a key component of fluid resuscitation. A single, reliable, and feasible physiological or biochemical parameter to define the balance between the changes in SV and oxygen delivery (i.e., coupling "macro" and "micro" circulation) is still not available, making the diagnosis of acute circulatory dysfunction primarily clinical.

Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study.

BACKGROUND: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates. METHODS: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters. RESULTS: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers. CONCLUSIONS: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies. TRIAL REGISTRATION: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.

Dynamic changes of pulse pressure but not of pulse pressure variation during passive leg raising predict preload responsiveness in critically ill patients with spontaneous breathing activity.

PURPOSE: To evaluate whether the changes in arterial pulse pressure (PP) and/or pulse pressure variation (PPV) during passive leg raising (PLR) can be used to evaluate preload responsiveness in patients with spontaneous breathing activity. MATERIALS AND METHODS: Patients ventilated with pressure support mode or totally spontaneously breathing were prospectively included. The values of PP and PPV were recorded before and at the end of PLR. The changes in cardiac index (CI) or the velocity-time integral (VTI) of the left ventricular outflow tract during PLR were tracked by the pulse contour analysis or transthoracic echocardiography. Patients exhibiting an increase in CI ≥ 10% or VTI ≥ 12% during PLR were defined as preload responders. RESULTS: Among 33 patients included, 28 (80%) received norepinephrine and 14 were preload responders. The increase in PP > 2 mmHg in absolute value (4% in percentage) during PLR (PLRPP) predicted preload responsiveness with an area under the receiver operating characteristic (AUROC) of 0.76 ± 0.09 (p = 0.003 vs. AUROC of 0.5). The changes in PPV during PLR, however, failed to predict preload responsiveness (p = 0.82 vs. AUROC of 0.5). CONCLUSION: In patients with full spontaneous breathing activity, PLR-induced changes in PP had a fair ability to assess preload responsiveness even when norepinephrine was administered. REGISTRATION NUMBER: ClinicalTrials.gov (NCT04369027).

Effective hemodynamic monitoring.

Hemodynamic monitoring is the centerpiece of patient monitoring in acute care settings. Its effectiveness in terms of improved patient outcomes is difficult to quantify. This review focused on effectiveness of monitoring-linked resuscitation strategies from: (1) process-specific monitoring that allows for non-specific prevention of new onset cardiovascular insufficiency (CVI) in perioperative care. Such goal-directed therapy is associated with decreased perioperative complications and length of stay in high-risk surgery patients. (2) Patient-specific personalized resuscitation approaches for CVI. These approaches including dynamic measures to define volume responsiveness and vasomotor tone, limiting less fluid administration and vasopressor duration, reduced length of care. (3) Hemodynamic monitoring to predict future CVI using machine learning approaches. These approaches presently focus on predicting hypotension. Future clinical trials assessing hemodynamic monitoring need to focus on process-specific monitoring based on modifying therapeutic interventions known to improve patient-centered outcomes.

Ten actions to achieve gender equity among intensivists: the French Society of Intensive Care (FICS) model.

In our recent survey, we aimed to collect information on perceived inequity as well as professional and personal fulfillment among women intensivists in France. For the 371 respondents out of the 732 persons who received the survey, the findings were unequivocal: for one-third of the respondents, being a woman was considered as an obstacle to careers or academic advancement, and for two thirds, pregnancy was viewed as a barrier to their career advancement. Gender discrimination had been experienced by 55% of the respondents. In 2019, to promote and achieve gender equity in the French Intensive Care Society (FICS), ten actions were initiated and are detailed in the present manuscript together with supporting data: (1) creation of a working group: the FEMMIR group; (2) promotion of mentorship; (3) implementation of concrete sponsorship; (4) transparency and public reporting of gender ratios in editorial boards; (5) workshops dedicated to unconscious gender bias; (6) workshops dedicated to improved women assertiveness; (7) role models; (8) creation of educational/information programs for young intensivists; (9) development of research on gender inequity and, as a perspective; and (10) development of a wide-ranging program. This review is aimed at providing a toolbox of organizational best practices designed to achieve gender equity. It is particularly important to share promising practical action engaged in our FEMMIR group with other concerned professionals around the world.

Combining fluids and vasopressors: A magic potion?

Early detection and prompt reversal of sepsis-induced tissue hypoperfusion are key elements while treating patients with septic shock. Fluid administration is widely accepted as the first-line therapy followed by vasopressor use in persistently hypotensive patients or in those with insufficient arterial pressure to ensure adequate tissue perfusion. Recent evidence suggests a beneficial effect of combining fluids with vasopressors in the early phase of sepsis. Compared with fluids alone, combining fluids and vasopressors increases mean systemic pressure and venous return and corrects hypotension better. This approach also limits fluid overload, which is an independent factor of poor outcomes in sepsis. It produces less hemodilution than fluids alone. As a consequence of these effects, combined treatment may improve outcomes in septic shock patients.

Current practice and evolving concepts in septic shock resuscitation.

Clinical and pathophysiological understanding of septic shock has progressed exponentially in the previous decades, translating into a steady decrease in septic shock-related morbidity and mortality. Even though large randomized, controlled trials have addressed fundamental aspects of septic shock resuscitation, many questions still exist. In this review, we will describe the current standards of septic shock resuscitation, but the emphasis will be placed on evolving concepts in different domains such as clinical resuscitation targets, adequate use of fluids and vasoactive drugs, refractory shock, and the use of extracorporeal therapies. Multiple research opportunities remain open, and collaborative endeavors should be performed to fill in these gaps.