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Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations. Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding. Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.

Background A peripheral perfusion-targeted resuscitation during early septic shock has shown encouraging results. Capillary refill time, which has a prognostic value, was used. Adding accuracy and predictability on capillary refill time (CRT) measurement, if feasible, would benefit to peripheral perfusion-targeted resuscitation. We assessed whether a reduction of capillary refill time during passive leg raising (ΔCRT-PLR) predicted volume-induced peripheral perfusion improvement defined as a significant decrease of capillary refill time following volume expansion. Methods Thirty-four patients with acute circulatory failure were selected. Haemodynamic variables, metabolic variables (PCO 2 gap), and four capillary refill time measurements were recorded before and during a passive leg raising test and after a 500-mL volume expansion over 20 min. Receiver operating characteristic curves were built, and areas under the curves were calculated (ROC AUC ). Confidence intervals (CI) were performed using a bootstrap analysis. We recorded mortality at day 90. Results The least significant change in the capillary refill time was 25% [95% CI, 18–30]. We defined CRT responders as patients showing a reduction of at least 25% of capillary refill time after volume expansion. A decrease of 27% in ΔCRT-PLR predicted peripheral perfusion improvement with a sensitivity of 87% [95% CI, 73–100] and a specificity of 100% [95% CI, 74–100]. The ROC AUC of ΔCRT-PLR was 0.94 [95% CI, 0.87–1.0]. The ROC AUC of baseline capillary refill time was 0.73 [95% CI, 0.54–0.90] and of baseline PCO 2 gap was 0.79 [0.61–0.93]. Capillary refill time was significantly longer in non-survivors than in survivors at day 90. Conclusion ΔCRT-PLR predicted peripheral perfusion response following volume expansion. This simple low-cost and non-invasive diagnostic method could be used in peripheral perfusion-targeted resuscitation protocols. Trial registration CPP Lyon Sud-Est II ANSM: 2014-A01034-43 Clinicaltrial.gov, NCT02248025 , registered 13th of September 2014

To estimate the incidence of active bleeding after cardiac surgery (AB) based on a definition directly related on blood flow from chest drainage; to describe the AB characteristics and its management; to identify factors of postoperative complications. AB was defined as a blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation for hemostasis during the first 12 postoperative hours. The definition was applied in a prospective longitudinal observational study involving 29 French centers; all adult patients undergoing cardiac surgery with cardiopulmonary bypass were included over a 3-month period. Perioperative data (including blood product administration) were collected. To study possible variation in clinical practice among centers, patients were classified into two groups according to the AB incidence of the center compared to the overall incidence: \"Low incidence\" if incidence is lower and \"High incidence\" if incidence is equal or greater than overall incidence. Logistic regression analysis was used to identify risk factors of postoperative complications. Among 4,904 patients, 129 experienced AB (2.6%), among them 52 reoperation. Postoperative bleeding loss was 1,000 [820;1,375] ml and 1,680 [1,280;2,300] ml at 6 and 24 hours respectively. Incidence of AB varied between centers (0 to 16%) but was independent of in-centre cardiac surgical experience. Comparisons between groups according to AB incidence showed differences in postoperative management. Body surface area, preoperative creatinine, emergency surgery, postoperative acidosis and red blood cell transfusion were risk factors of postoperative complication. A blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or early reoperation for hemostasis seems a relevant definition of AB. This definition, independent of transfusion, adjusted to body weight, may assess real time bleeding occurring early after surgery.

New-onset postoperative atrial fibrillation (POAF) is common after cardiac and major noncardiac surgery and significantly associated with short- and long-term adverse events. Multiple management strategies have been described but the lack of evidence from large randomized controlled trials and the lack of consensus regarding best practices has led to major variations in practice patterns. Considering on the one hand its serious adverse effects and complex drug interactions, and on the other hand discrepancies among recent international guidelines, the indications of amiodarone to both prevent and treat POAF should be reserved to patients at high risk of POAF only, or patients with hemodynamic instability and/or severely reduced left ventricular ejection fraction. Perioperative optimization of oral and intravenous cardio-selective beta-blockers to prevent POAF, and control heart rate when POAF occurs with a rapid ventricular response is the recommended first-line strategy, simultaneously with the treatment of associated factors. Given their efficient and safe profile, ultra-short-acting intravenous beta-blockers like esmolol or landiolol could be preferentially used in acute care patients. Besides waiting for the results of ongoing RCTs in cardiac and noncardiac surgery, the use of oral anticoagulation in patients with POAF should take into account the individualized thromboembolic/hemorrhagic risk ratio.

[...]the “de-escalation” phase consists in fluid removal if a negative fluid balance is not spontaneously achieved, to counteract the side effects inherent to the initial resuscitation and fluid creep. In this situation, we believe that the adequacy between vascular refilling and fluid removal rates is the cornerstone of hemodynamic stability. [...]limiting fluid removal to patients with preload unresponsiveness may seriously limit the eligible population. Association of net ultrafiltration rate with mortality among critically ill adults with acute kidney injury receiving continuous venovenous hemodiafiltration: a secondary analysis of the Randomized evaluation of normal vs augmented level (RENAL) of Renal replacement therapy trial.

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

Cardiac surgery with cardiopulmonary bypass results in global myocardial ischemia–reperfusion injury, leading to significant postoperative morbidity and mortality. Although cardioplegia is the cornerstone of intraoperative cardioprotection, a number of additional strategies have been identified. The concept of preconditioning and postconditioning, despite its limited direct clinical application, provided an essential contribution to the understanding of myocardial injury and organ protection. Therefore, physicians can use different tools to limit perioperative myocardial injury. These include the choice of anesthetic agents, remote ischemic preconditioning, tight glycemic control, optimization of respiratory parameters during the aortic unclamping phase to limit reperfusion injury, appropriate choice of monitoring to optimize hemodynamic parameters and limit perioperative use of catecholamines, and early reintroduction of cardioprotective agents in the postoperative period. Appropriate management before, during, and after cardiopulmonary bypass will help to decrease myocardial damage. This review aimed to highlight the current advancements in cardioprotection and their potential applications during cardiac surgery.

Background It is uncertain whether fluid administration can improve patients with systemic venous congestion and haemodynamic instability. This study aimed to describe the changes in systemic venous congestion and peripheral perfusion parameters induced by a fluid challenge in these patients, and to analyse the influence of the fluid responsiveness status on these changes. Methods The study is a single-centre prospective cohort study of 36 critically ill ICU patients with haemodynamic instability and a maximum vena cava diameter ≥ 20 mm. Changes in cardiac index during a fluid challenge (4 mL/kg of lactated Ringer’s solution during 5 min) assessed by pulse contour analysis, central venous pressure, ultrasound systemic congestion parameters (portal venous flow pulsatility index, supra hepatic and intrarenal venous Doppler), and peripheral perfusion parameters (capillary refill time and peripheral perfusion index) were assessed in the overall population. All these data were compared between patients presenting a cardiac index increase > 10% during the fluid challenge (fluid responders) and the others (fluid non-responders). Results Twenty-eight (78%) patients were admitted for postoperative care following cardiac surgery; their mean ± SD left ventricular ejection fraction was 42 ± 9% and right ventricular dysfunction was found in at least 61% of the patients. The mean ± SD SOFA score was 9 ± 3. Thirteen (36%) patients were fluid responders. The fluid challenge administration induced a significant increase in portal pulsatility index, VExUS score, and central venous pressure without significant difference of these changes between fluid responders and non-responders. No significant change in perfusion parameters was observed. Conclusion Fluid administration in patients with haemodynamic instability and systemic venous congestion worsens venous congestion regardless of the fluid responsiveness status, without improving perfusion parameters.

Background A recent study suggested that point-of-care ultrasound (POCUS) venous congestion assessment poorly describes the changes in venous return during a fluid challenge. The aim of the present study was to explore the relationship between POCUS venous congestion assessment parameters and the determinants of venous return in steady state and during a fluid challenge. Methods This study is a post-hoc analysis of a single-centre prospective cohort study of patients presenting acute circulatory failure and venous congestion. The protocol consisted in a fluid administration of 4mL/kg over five minutes, just preceded and followed by the acquisition of haemodynamic data and POCUS venous congestion assessment parameters (VExUS score and portal pulsatility index, PPi). Venous return (dVR) was defined as the difference between mean systemic filling pressure analogue estimated by the mathematical approach of Parkin and Leaning (Pmsa) and central venous pressure (CVP). Relationships between Pmsa, CVP, dVR, and VExUS score and PPi were analysed using linear regression and Jonckheere-Terpstra test for trend. Results Thirty-two patients were included in the analysis. Fluid challenge induced a significant increase in CVP, Pmsa, dVR, and VExUS score. In steady state, there was a significant association of VExUS score and PPi with CVP ( P- value = 0.006 and 0.002, respectively) and Pmsa ( P- value = 0.004 and 0.003, respectively) but not with dVR ( P- value = 0.943 and 0.408, respectively). The variations induced by fluid challenge in CVP, Pmsa and dVR were not associated with variations in PPi ( P- value = 0.844, 0.912 and 0.716, respectively). Patients without VExUS score increase during the fluid challenge presented a higher increase in Pmsa than patients with an increase in VExUS score. Conclusion In steady state, POCUS venous congestion assessment parameters are associated with CVP and Pmsa but not with dVR. After fluid administration, changes in POCUS venous congestion assessment parameters were not associated with changes in CVP, Pmsa, and dVR.

Background Fibrinogen concentrate may reduce allogeneic blood product transfusion in cardiac surgery patients with bleeding associated with acquired hypofibrinogenemia. The European Society of Anaesthesiology and Intensive Care (ESAIC) has issued guidelines, but compliance to these guidelines has not been studied yet. Methods This multicentre observational cohort study was aimed at evaluating the compliance of fibrinogen prescription with ESAIC. Adult patients undergoing cardiac surgery with cardiopulmonary bypass in 13 French cardiac surgery centres were recruited from March 2017 to April 2018. Compliance with ESAIC guidelines was considered whenever patients received fibrinogen in case of hypofibrinogenemia and clinically relevant bleeding, or when patients did not receive fibrinogen concentrate if there was no hypofibrinogenemia and/or no clinically relevant bleeding. The primary endpoint was the percentage of patients who complied those guidelines. Secondary endpoints were to assess the consequences of non-compliance on in-hospital deaths and hospital length-of-stay. Results Among 2,649 adult patients undergoing cardiac surgery with cardiopulmonary bypass, 374 (14.1%) received fibrinogen concentrate. Rates of prescription among centres varied from < 1.0% to 31.2% ( p  < 0.001). Compliance with guidelines was observed in 2,291 (86.5%) patients, driven by a high number of patients without prescription ( N  = 2,158; 94.5%). In non-compliance patients ( N  = 358; 13.5%), fibrinogen over-prescription ( N  = 241) exceeded under-prescription ( N  = 117). In multivariate analyses, non-compliance with the guidelines was not significantly associated with in-hospital deaths or hospital stay. Conclusions Fibrinogen concentrate prescription varied significantly among centres but compliance with the ESAIC guidelines was high (86.5%). Non-compliance (13.5%)—mostly due to over-prescription—was not associated with adverse outcomes. Trial registration Clinicaltrials.gov identifier: (NCT03075774).