ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation.

BACKGROUND: In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. AIMS: The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. METHODS: The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. RESULTS: In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. CONCLUSION: The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

Cost Analysis of Aprotinin Reintroduction in French Cardiac Surgery Centres: A Real-World Data-Based Analysis.

INTRODUCTION: The European Medicines Agency restored aprotinin (APR) use for preventing blood loss in patients undergoing isolated coronary artery bypass graft (iCABG) in 2016 but requested the collection of patient and surgery data in a registry (NAPaR). The aim of this analysis was to evaluate the impact of APR reintroduction in France on the main hospital costs (operating room, transfusion and intensive unit stay) compared to the current use of tranexamic acid (TXA), which was the only antifibrinolytic available before APR reinstatement. METHODS: A multicenter before-after post-hoc analysis to compare APR and TXA was carried out in four French university hospitals. APR use followed the ARCOTHOVA (French Association of Cardiothoracic and Vascular Anesthetists) protocol, which had framed three main indications in 2018. Data from 236 APR patients were retrieved from the NAPaR (N = 874); 223 TXA patients were retrospectively retrieved from each center database and matched to APR patients upon indication classes. Budget impact was evaluated using both direct costs associated with antifibrinolytics and transfusion products (within the first 48 h) and other costs such as surgery duration and ICU stay. RESULTS: The 459 collected patients were distributed as: 17% on-label; 83% off-label. Mean cost per patient until ICU discharge tended to be lower in the APR group versus the TXA group, which resulted in an estimated gross saving of €3136 per patient. These savings concerned operating room and transfusion costs but were mainly driven by reduced ICU stays. When extrapolated to the whole French NAPaR population, the total savings of the therapeutic switch was estimated at around €3 million. CONCLUSION: The budget impact projected that using APR according to ARCOTHOVA protocol resulted in decreased requirement for transfusion and complications related to surgery. Both were associated with substantial cost savings from the hospital's perspective compared with exclusive use of TXA.

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

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.

Assessment of changes in blood glucose concentration with intravascular microdialysis.

Blood glucose and its variability of is a major prognostic factor associated with morbidity. We hypothesized that intravenous microdialysis incorporated in a central venous catheter (CVC) would be interchangeable with changes in blood glucose measured by the reference method using a blood gas analyzer. Microdialysis and central venous blood glucose measurements were simultaneously recorded in high-risk cardiac surgical patients. The correlation between absolute values was determined by linear regression and the Bland-Altman test for repeated measurements was used to compare bias, precision, and limits of agreement. Changes in blood glucose measurement were evaluated by four-quadrant plot and trend interchangeability methods (TIM). In the 23 patients analyzed, the CVC was used as part of standard care with no complications. The correlation coefficient for absolute values (N = 99) was R = 0.91 (P < 0.001). The bias, precision and limits of agreement were - 9.1, 17.4 and - 43.2 to 24.9 mg/dL, respectively. The concordance rate for changes in blood glucose measurements (N = 77) was 85% with the four-quadrant plot. The TIM showed that 14 (18%) changes of blood glucose measurements were uninterpretable. Among the remaining 63 (82%) interpretable changes, 23 (37%) were interchangeable, 13 (20%) were in the gray zone, and 27 (43%) were not interchangeable. Microdialysis using a CVC appears to provide imprecise absolute blood glucose values with risk of insulin misuse. Moreover, only one third of changes in blood glucose measurements were interchangeable with the reference method using the TIM.

Assessment of macro- and micro-oxygenation parameters during fractional fluid infusion: A pilot study.

PURPOSE: The main goal of this study was to assess whether maximal fluid infusion improves both oxygen delivery (DO2) and micro-circulatory parameters during hemodilution. The secondary objective was to assess the ability of baseline micro-circulatory parameters to predict oxygen consumption (VO2) response following fluid infusion. MATERIALS AND METHODS: In a postoperative cardiac ICU, patients received repeated fluid infusion until stroke volume (SV) was maximized. Before and after each fluid expansion, macro- (DO2, VO2) and micro-circulatory oxygenation parameters were recorded [central venous oxygen saturation (ScVO2), blood lactate, difference in veno-arterial carbon dioxide tension (P(v-a)CO2), somatic and cerebral oxygen saturation (rSO2)]. Patients were classified as VO2-Responders or VO2-Non-Responders according to an increase in VO2 above or below 15%, respectively. RESULTS: After maximal fluid infusion, all patients showed improved macro- and micro-circulatory oxygenation parameters, but VO2-Responders had lower values (especially for ScVO2 and cerebral rSO2). Only baseline ScVO2 and cerebral rSO2 were useful to predict the VO2 response to maximal fluid infusion (ROCAUC 0.80 (95% CI: 0.54-0.95, P=0.012) and 0.83 (95% CI: 0.57-0.96, P=0.001). CONCLUSIONS: Maximal fluid infusion improves macro- and micro-circulatory oxygenation parameters. For VO2-Responders, only ScVO2 and cerebral rSO2 could serve as markers of tissue hypoxia.

Assessment of changes in cardiac index with calibrated pulse contour analysis in cardiac surgery: A prospective observational study.

OBJECTIVES: To assess the trending ability of calibrated pulse contour cardiac index (CIPC) monitoring during haemodynamic changes (passive leg raising [PLR] and fluid loading) compared with transpulmonary thermodilution CI (CITD). METHOD: Seventy-eight mechanically-ventilated patients admitted to intensive care with calibrated pulse contour following cardiac surgery were prospectively included and investigated during PLR, and after fluid loading. Fluid responsiveness was defined as a≥15% CITD increase after a 500ml bolus. Areas under the empiric receiver operating characteristic curves (ROCAUC) for changes in CIPC (ΔCIPC) during PLR to predict fluid responsiveness and after fluid challenge to predict an increase at least 15% in CITD after fluid loading were calculated. RESULTS: Fifty-five patients (71%) were classified as responders, 23 (29%) as non-responders. ROCAUC for ΔCIPC during PLR in predicting fluid responsiveness, its sensitivity, specificity, and percentage of patients within the inconclusive class of response were 0.67 (95% CI=0.55-0.77), 0.76 (95% CI=0.63-0.87), 0.57 (95% CI=0.34-0.77) and 68%, respectively. Bias, precision and limits of agreements and percentage error between CIPC and CITD after fluid challenge were 0.14 (95% CI: 0.08-0.20), 0.26, -0.37 to 0.64 l min(-1)m(-2), and 20%, respectively. The concordance rate was 97% and the polar concordance at 30° was 91%. ROCAUC for ΔCIPC in predicting an increase of at least 15% in CITD after fluid loading was 0.85 (95% CI: 0.76-0.92). CONCLUSION: Although ΔCIPC after fluid loading could track the direction of changes of CITD and was interchangeable with bolus transpulmonary thermodilution, PLR could not predict fluid responsiveness in cardiac surgery patients.

Noninvasive assessment of peripheral microcirculation by near-infrared spectroscopy: a comparative study in healthy smoking and nonsmoking volunteers.

Smokers are exposed to early endothelial dysfunction. This microcirculatory damage can be demonstrated by near-infrared spectroscopy (NIRS). The aim of this study was to compare microvascular reactivity by NIRS during a dynamic vascular occlusion test in healthy smokers and nonsmokers volunteers. Twenty healthy volunteers (10 men, 10 women), aged from 22 to 38 years old, were included after approval of the local Ethics Committee and divided into two groups: smokers (n = 10) and nonsmokers (n = 10). Tissue oxygen saturation (StO2) was measured at the level of each individual's calves during an ischemia and reperfusion test. In addition, during the ischemia phase, the slope of decline in StO2 was determined. Therefore, for each group, we were able to deduce the speed of desaturation (ΔStO2/ischemia time). The same was applied for resaturation rates during the reperfusion phase (ΔStO2/reperfusion time). StO2 values were comparable at all experimental steps between smokers and nonsmokers. During the vascular occlusion test, rates of desaturation were the same between smokers and nonsmokers [respectively 3.7%·min(-1) (range 2.5-12.6) and 3.7%·min(-1) (range 1.8-15.1); p = 0.50]. It was the same for the rate of resaturation [smokers 30.4%·min(-1) (range 14.2-51.6) and nonsmokers 30.5%·min(-1) (range 18.6-44.5); p = 0.82]. NIRS study of microvascular reactivity during a dynamic vascular occlusion test did not reveal any difference between smokers and nonsmokers. Therefore, NIRS could not be sensitive enough to highlight endothelial dysfunction in healthy subjects exposed to tobacco smoke.

Noninvasive assessment of cardiac index in healthy volunteers: a comparison between thoracic impedance cardiography and Doppler echocardiography.

BACKGROUND: Thoracic bioimpedance cardiography (ICG) has been proposed as a noninvasive, continuous, operator-independent, and cost-effective method for cardiac output monitoring. In the present study, we compared cardiac index (CI) measurements with ICG (Niccomo device) and transthoracic Doppler echocardiography in resting healthy volunteers undergoing hemodynamic load challenge. METHODS: Twenty-five healthy volunteers (7 men and 18 women, mean age 36 +/- 6 yr, body surface area 1.75 +/- 0.17 m(2)) were investigated during three experimental conditions: baseline, positive end-expiratory pressure + 10 cm H(2)O and lower body positive pressure by means of medical antishock trousers inflated to 30 cm H(2)O in the abdominal compartment. RESULTS: ICG signal quality was >89% over all sets of measurements. A weak but significant relationship was observed between CI(TTE) and CI(ICG) (r = 0.36; P = 0.002). Agreement between both techniques was 0.94 L x min(-1) x m(-2) (95% CI: 0.77-1.11), limits of agreement were -0.47 to 2.35 L x min(-1) x m(-2), and percentage error was 53%. No statistically significant relationships were found between percent changes in CI(TTE) and CI(ICG) after applications of positive end-expiratory pressure + 10 cm H(2)O (r = 0.21; P = 0.31) and medical antishock trousers (r = 0.22; P = 0.30). CONCLUSIONS: Poor correlation and lack of agreement between absolute values of CI measured by ICG and transthoracic Doppler echocardiography were found in resting healthy volunteers. The Niccomo device was also unreliable for monitoring changes in CI during hemodynamic load challenge.