Mortality after coronary artery bypass grafting (CABG) surgery declined from 2.4% to less than 1.5% between 1994 and 2009, but remained much higher (17% to 24%) in the subgroup of patients who developed a postoperative low cardiac output syndrome.¹ The prevalence of low cardiac output syndrome after CABG surgery varies from 3% to 14%, but the presence of a preoperative left ventricular dysfunction, ie, a left ventricular ejection fraction less than or equal to 40%, is associated with an odds ratio of 2.0 (95% CI 1.7-2.4).¹ Quiz Ref ID The low cardiac output syndrome is also associated with more frequent complications, including pulmonary impairment, myocardial infarction, stroke, and renal failure.²

Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.)

Background. The aim of this study was to evaluate potential predictors of fluid responsiveness obtained during major hepatic surgery. The predictors studied were invasive monitoring of intravascular pressures (radial and pulmonary artery catheter), including direct measurement of respiratory variation in arterial pulse pressure (PPVart), transoesophageal echocardiography (TOE), and non-invasive estimates of PPVart from the infrared photoplethysmography waveform from the Finapres^® (PPVfina) and the pulse oximetry waveform (PPVsat). Methods. We conducted a prospective study of 54 fluid challenges (250 ml colloid) given for haemodynamic instability in eight patients undergoing hepatic resection. Fluid responsiveness was defined as an increase in stroke volume index (SVI) ≥10%. The following variables were recorded before each fluid challenge: right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), PPVart, PPVfina, PPVsat, and the TOE-derived variables left ventricular end-diastolic area index (LVEDAI), early/late (E/A) diastolic filling wave ratio, deceleration time of the E wave (MDT) of mitral flow and the systolic fraction of the pulmonary venous flow (SF). Results. Only PPVfina, PPVart (both P<0.001), PPVsat (P=0.02), LVEDAI and MDT (both P=0.04) were different in responder vs non-responder fluid challenges. The areas under the receiver operating characteristic (ROC) curves were 0.81 (PPVfina), 0.79 (PPVart), 0.70 (LVEDAI), 0.68 (PPVsat and MDT), 0.63 (RAP), 0.62 (E/A), 0.55 (PAOP) and 0.42 (SF). The areas under the ROC curves for RAP, E/A, PAOP and SF were significantly less than that for PPVfina (P<0.05 in each case). Only PPVart (r=0.59, P=0.0001) and PPVfina (r=0.56, P=0.0001) correlated with the fluid challenge-induced changes in SVI. Conclusions. PPVart and PPVfina predict fluid responsiveness during major hepatic surgery. This suggests that intraoperative monitoring of fluid responsiveness may be implemented simply and non-invasively.

Introduction: Central venous oxygen saturation (ScvO₂) is a useful therapeutic target in septic shock and high-risk surgery. We tested the hypothesis that central venous-to-arterial carbon dioxide difference (P(cv-a)CO₂), a global index of tissue perfusion, could be used as a complementary tool to ScvO₂ for goal-directed fluid therapy (GDT) to identify persistent low flow after optimization of preload has been achieved by fluid loading during high-risk surgery. Methods: This is a secondary analysis of results obtained in a study involving 70 adult patients (ASA I to III), undergoing major abdominal surgery, and treated with an individualized goal-directed fluid replacement therapy. All patients were managed to maintain a respiratory variation in peak aortic flow velocity below 13%. Cardiac index (CI), oxygen delivery index (DO₂i), ScvO₂, P(cv-a)CO₂ and postoperative complications were recorded blindly for all patients. Results: A total of 34% of patients developed postoperative complications. At baseline, there was no difference in demographic or haemodynamic variables between patients who developed complications and those who did not. In patients with complications, during surgery, both mean ScvO₂ (78 ± 4 versus 81 ± 4%, P = 0.017) and minimal ScvO₂ (minScvO₂) (67 ± 6 versus 72 ± 6%, P = 0.0017) were lower than in patients without complications, despite perfusion of similar volumes of fluids and comparable CI and DO₂i values. The optimal ScvO₂ cut-off value was 70.6% and minScvO₂ < 70% was independently associated with the development of postoperative complications (OR = 4.2 (95% CI: 1.1 to 14.4), P = 0.025). P(cv-a)CO₂ was larger in patients with complications (7.8 ± 2 versus 5.6 ± 2 mmHg, P < 10^-6). In patients with complications and ScvO₂ ≥71%, P(cv-a)CO₂ was also significantly larger (7.7 ± 2 versus 5.5 ± 2 mmHg, P < 10^-6) than in patients without complications. The area under the receiver operating characteristic (ROC) curve was 0.785 (95% CI: 0.74 to 0.83) for discrimination of patients with ScvO₂ ≥71% who did and did not develop complications, with 5 mmHg as the most predictive threshold value. Conclusions: ScvO₂ reflects important changes in O₂ delivery in relation to O₂ needs during the perioperative period. A P(cv-a)CO₂ < 5 mmHg might serve as a complementary target to ScvO₂ during GDT to identify persistent inadequacy of the circulatory response in face of metabolic requirements when an ScvO₂ ≥71% is achieved. Trial registration: Clinicaltrials.gov Identifier: NCT00852449.

A low dose (0.5 mg/kg) of lipopolysaccharide (LPS), administered 72 hours before 60-minute middle cerebral artery occlusion, induced a delayed neuroprotection proven by the significant decrease (–35%) of brain infarct volume in comparison with control, whereas infarct volumes remained unchanged in rats treated 12, 24, or 168 hours before ischemia. This delayed neuroprotective effect of LPS was induced only with low doses (0.25 to 1 mg/kg), whereas this effect disappeared with a higher dose (2 mg/kg). The delayed neuroprotection of LPS was induced in the cortical part of the infarcted zone, not in the subcortical part. The beneficial effect of LPS on consequences of middle cerebral artery occlusion was suppressed by dexamethasone (3 mg/kg) and indomethacin (3 mg/kg) administered 1 hour before LPS, whereas both drugs had no direct effect on infarct volume by themselves, suggesting that activation of inflammatory pathway is involved in the development of LPS-induced brain ischemic tolerance. Preadministration of cycloheximide, an inhibitor of protein synthesis, also blocked LPS-induced brain ischemic tolerance suggesting that a protein synthesis is also necessary as a mediating mechanism. Superoxide dismutase (SOD) could be one of the synthesized proteins because lipopolysaccharide increased SOD brain activity 72 hours, but not 12 hours, after its administration, which paralleled the development of brain ischemic tolerance. In contrast, catalase brain activity remained unchanged after LPS administration. The LPS-induced delayed increase in SOD brain content was suppressed by a previous administration of indomethacin. These data suggest that the delayed neuroprotective effect of low doses of LPS is mediated by an increased synthesis of brain SOD that could be triggered by activation of inflammatory pathway.