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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.

Despite a large body of evidence, the implementation of guidelines on hemodynamic optimization and goal-directed therapy remains limited in daily routine practice. To facilitate/accelerate this implementation, a panel of experts in the field proposes an approach based on six relevant questions/answers that are frequently mentioned by clinicians, using a critical appraisal of the literature and a modified Delphi process. The mean arterial pressure is a major determinant of organ perfusion, so that the authors unanimously recommend not to tolerate absolute values below 65 mmHg during surgery to reduce the risk of postoperative organ dysfunction. Despite well-identified limitations, the authors unanimously propose the use of dynamic indices to rationalize fluid therapy in a large number of patients undergoing non-cardiac surgery, pending the implementation of a “validity criteria checklist” before applying volume expansion. The authors recommend with a good agreement mini- or non-invasive stroke volume/cardiac output monitoring in moderate to high-risk surgical patients to optimize fluid therapy on an individual basis and avoid volume overload. The authors propose to use fluids and vasoconstrictors in combination to achieve optimal blood flow and maintain perfusion pressure above the thresholds considered at risk. Although purchase of disposable sensors and stand-alone monitors will result in additional costs, the authors unanimously acknowledge that there are data strongly suggesting this may be counterbalanced by a sustained reduction in postoperative morbidity and hospital lengths of stay. Beside existing guidelines, knowledge and explicit clinical reasoning tools followed by decision algorithms are mandatory to implement individualized hemodynamic optimization strategies and reduce postoperative morbidity and duration of hospital stay in high-risk surgical patients.

Concerns have been raised about the predictive performance (PP) of the EuroSCORE I (ES I) to estimate operative mortality (OM) of patients aged ≥80. The EuroSCORE II (ES II) has been described to have better PP of OM but external validations are scarce. Furthermore, the PP of ES II has not been investigated among the octogenarians. The goal of the study was to compare the PP of ES II and ES I among the overall population and patients ≥ 80. The ES I and ES II were computed for 7161 consecutive patients who underwent major cardiac surgery in a 7-year period. Discrimination was assessed by using the c- index and calibration with the Hosmer-Lemeshow (HL) and calibration plot by comparing predicted and observed mortality. From the global cohort of 7161 patients, 832 (12%) were ≥80. The mean values of ES I and ES II were 7.4±9.4 and 5.2±9.1 respectively for the whole cohort, 6.3±8.6 and 4.7±8.5 for the patients <80, 15.1±11.8 and 8.5±11.0 for the patients ≥80. The mortality was 9.38% (≥80) versus 5.18% (<80). The discriminatory power was good for the two algorithms among the whole population and the <80 but less satisfying among the ≥80 (AUC 0.64 [0.58-0.71] for ES I and 0.67 [0.60-0.73] for the ES II without significant differences (p = 0.35) between the two scores. For the octogenarians, the ES II had a fair calibration until 10%-predicted values and over-predicted beyond. The ES II has a better PP than the ES I among patients <80. Its discrimination and calibration are less satisfying in patients ≥80, showing an overestimation in the elderly at very high-surgical risk. Nevertheless, it shows an acceptable calibration until 10%- predicted mortality.

Electroencephalography (EEG) signals contain transient oscillation patterns commonly used to classify brain states in responses to action, sleep, coma or anesthesia. Using a time-frequency analysis of the EEG, we search for possible causal correlations between the successive phases of general anesthesia. We hypothesize that it could be possible to anticipate recovery patterns from the induction or maintenance phases. For that goal, we track the maximum power of the α-band and follow its time course. We quantify the frequency shift of the α-band during the recovery phase and the associated duration. Using Pearson coefficient and Bayes factor, we report non-significant linear correlation between the α-band frequency and duration shifts during recovery and the presence of the δ or the α rhythms during the maintenance phase. We also found no correlations between the α-band emergence trajectory and the total duration of the flat EEG epochs (iso-electric suppressions) induced by a propofol bolus injected during induction. Finally, we quantify the instability of the α-band using the mathematical total variation that measures possible deviations from a flat line. To conclude, the present correlative analysis shows that EEG dynamics extracted from the initial and maintenance phases of general anesthesia cannot anticipate both the emergence trajectory and the extubation time.

Perioperative anaphylaxis is a rare and acute systemic manifestation of drug-induced hypersensitivity reactions that occurs following anesthesia induction; the two main classes of drugs responsible for these reactions being neuromuscular blocking agents (NMBA) and antibiotics. The sensitization mechanisms to the drugs are not precisely known, and few risk factors have been described. A growing body of evidence underlines a link between occurrence of allergy and microbiota composition. However, no data exist on microbiota in perioperative anaphylaxis. The aim of this study was to compare circulating microbiota richness and composition between perioperative anaphylaxis patients and matched controls. Circulating 16s rDNA was quantified and sequenced in serum samples from 20 individuals with fully characterized IgE-mediated NMBA-related anaphylaxis and 20 controls matched on sex, age, NMBA received, type of surgery and infectious status. Microbiota composition was analyzed with a published bioinformatic pipeline and links with patients clinical and biological data investigated. Analysis of microbiota diversity showed that anaphylaxis patients seem to have a richer circulating microbiota than controls, but no major differences of composition could be detected with global diversity indexes. Pairwise comparison showed a difference in relative abundance between patients and controls for , and . Some taxa were associated with concentrations of mast cell tryptase and specific IgE. We did not find a global difference in terms of microbiota composition between anaphylaxis patient and controls. However, several taxa were associated with anaphylaxis patients and with their biological data. These findings must be further confirmed in different settings to broaden our understanding of drug anaphylaxis pathophysiology and identify predisposition markers.

Background The objectives of the present study was to evaluate the effect of fluid challenge (FC) on ventriculo-arterial (V-A) coupling, its determinants: arterial elastance and ventricular elastance, and ability to predict fluid responsiveness. Methods Thirty patients admitted to cardio-thoracic ICU in whom the physician decided to perform FC were included. Arterial pressure, cardiac output, arterial elastance, and ventricular elastance, were measured before and after FC with 500 ml of lactated Ringer’s solution. Fluid responders were defined as patients with more than a 15% increase in stroke volume. V-A coupling was evaluated by the arterial elastance to ventricular elastance ratio. Results Twenty-three (77%) of the 30 patients included in the study were fluid responders. Before FC, responders had higher arterial elastance and arterial elastance to ventricular elastance ratio. FC significantly increased mean arterial pressure, stroke volume and cardiac output, and significantly decreased systemic vascular resistance, arterial elastance and consequently the arterial elastance to ventricular elastance ratio. Changes in arterial elastance were correlated with changes in stroke volume, systemic vascular resistance, and arterial compliance. Baseline arterial elastance to ventricular elastance ratio over 1.4 predicted fluid responsiveness (area under the curve [95% confidence interval]: 0.84 [0.66–1]; p  < 0.0001). Conclusions Fluid responsiveness patients had V-A coupling characterized by increase arterial elastance to ventricular elastance ratio, in relation to an increase arterial elastance. Fc improved the V-A coupling ratio by decreasing arterial elastance without altering ventricular elastance. Arterial elastance changes were related to those of systemic vascular resistance (continue component) and of arterial compliance (pulsatile component).

Hydrogen sulfide (H2S) is a mediator with demonstrated protective effects for the cardiovascular system. On the other hand, prostaglandin (PG)E2 is involved in vascular wall remodeling by regulating matrix metalloproteinase (MMP) activities. We tested the hypothesis that endogenous H2S may modulate PGE2, MMP-1 activity and endogenous tissue inhibitors of MMPs (TIMP-1/-2). This regulatory pathway could be involved in thinning of abdominal aortic aneurysm (AAA) and thickening of saphenous vein (SV) varicosities. The expression of the enzyme responsible for H2S synthesis, cystathionine-γ-lyase (CSE) and its activity, were significantly higher in varicose vein as compared to SV. On the contrary, the endogenous H2S level and CSE expression were lower in AAA as compared to healthy aorta (HA). Endogenous H2S was responsible for inhibition of PGE2 synthesis mostly in varicose veins and HA. A similar effect was observed with exogenous H2S and consequently decreasing active MMP-1/TIMP ratios in SV and varicose veins. In contrast, in AAA, higher levels of PGE2 and active MMP-1/TIMP ratios were found versus HA. These findings suggest that differences in H2S content in AAA and varicose veins modulate endogenous PGE2 production and consequently the MMP/TIMP ratio. This mechanism may be crucial in vascular wall remodeling observed in different vascular pathologies (aneurysm, varicosities, atherosclerosis and pulmonary hypertension).

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).

Varicose veins are elongated and dilated saphenous veins. Despite the high prevalence of this disease, its pathogenesis remains unclear. In this study, we investigated the control of matrix metalloproteinases (MMPs) expression by prostaglandin (PG)E₂ during the vascular wall remodeling of human varicose veins. Varicose (small (SDv) and large diameter (LDv)) and healthy saphenous veins (SV) were obtained after surgery. Microsomal and cytosolic PGE-synthases (mPGES and cPGES) protein and mRNA responsible for PGE₂ metabolism were analyzed in all veins. cPGES protein was absent while its mRNA was weakly expressed. mPGES-2 expression was similar in the different saphenous veins. mPGES-1 mRNA and protein were detected in healthy veins and a significant decrease was found in LDv. Additionally, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), responsible for PGE₂ degradation, was over-expressed in varicose veins. These variations in mPGES-1 and 15-PGDH density account for the decreased PGE₂ level observed in varicose veins. Furthermore, a significant decrease in PGE₂ receptor (EP4) levels was also found in SDv and LDv. Active MMP-1 and total MMP-2 concentrations were significantly decreased in varicose veins while the tissue inhibitors of metalloproteinases (TIMP -1 and -2), were significantly increased, probably explaining the increased collagen content found in LDv. Finally, the MMP/TIMP ratio is restored by exogenous PGE₂ in varicose veins and reduced in presence of an EP4 receptor antagonist in healthy veins. In conclusion, PGE₂ could be responsible for the vascular wall thickening in human varicose veins. This mechanism could be protective, strengthening the vascular wall in order to counteract venous stasis.