Perfusion quality odds (PEQUOD) trial: validation of the multifactorial dynamic perfusion index as a predictor of cardiac surgery-associated acute kidney injury.

OBJECTIVES: The multifactorial dynamic perfusion index was recently introduced as a predictor of cardiac surgery-associated acute kidney injury. The multifactorial dynamic perfusion index was developed based on retrospective data retrieved from the patient files. The present study aims to prospectively validate this index in an external series of patients, through an on-line measure of its various components. METHODS: Inclusion criteria were adult patients undergoing cardiac surgery with cardiopulmonary bypass. Data collection included preoperative factors and cardiopulmonary bypass-related factors. These were collected on-line using a dedicated monitor. Factors composing the multifactorial dynamic perfusion index are the nadir haematocrit, the nadir oxygen delivery, the time of exposure to a low oxygen delivery, the nadir mean arterial pressure, cardiopulmonary bypass duration, the use of red blood cell transfusions and the peak arterial lactates. RESULTS: Two hundred adult patients were investigated. The multifactorial dynamic perfusion index had a good (c-statistics 0.81) discrimination for cardiac surgery-associated acute kidney injury (any stage) and an excellent (c-statistics 0.93) discrimination for severe patterns (stage 2-3). Calibration was modest for cardiac surgery-associated acute kidney injury (any stage) and good for stage 2-3. The use of vasoconstrictors was an additional factor associated with cardiac surgery-associated acute kidney injury. CONCLUSIONS: The multifactorial dynamic perfusion index is validated for discrimination of cardiac surgery-associated acute kidney injury risk. It incorporates modifiable risk factors, and may help in reducing the occurrence of cardiac surgery-associated acute kidney injury.

Plasma-Free Strategy for Cardiac Surgery with Cardiopulmonary Bypass in Infants < 10 kg: A Retrospective, Propensity-Matched Study.

BACKGROUND: Infants < 10 kg undergoing cardiac surgery with cardiopulmonary bypass (CPB) may receive either fresh frozen plasma (FFP) or other solutions in the CPB priming volume. The existing comparative studies are controversial. No study addressed the possibility of total avoidance of FFP throughout the whole perioperative course in this patient population. This retrospective, non-inferiority, propensity-matched study investigates an FFP-free strategy compared to an FFP-based strategy. METHODS: Among patients <10 kg with available viscoelastic measurements, 18 patients who received a total FFP-free strategy were compared to 27 patients (1:1.5 propensity matching) receiving an FFP-based strategy. The primary endpoint was chest drain blood loss in the first 24 postoperative hours. The level of non-inferiority was settled at a difference of 5 mL/kg. RESULTS: The 24-h chest drain blood loss difference between groups was -7.7 mL (95% confidence interval -20.8 to 5.3) in favor of the FFP-based group, and the non-inferiority hypothesis was rejected. The main difference in coagulation profile was a lower level of fibrinogen concentration and FIBTEM maximum clot firmness in the FFP-free group immediately after protamine, at the admission in the ICU and for 48 postoperative hours. No differences in transfusion of red blood cells or platelet concentrate were observed; patients in the FFP-free group did not receive FFP but required a larger dose of fibrinogen concentrate and prothrombin complex concentrate. CONCLUSIONS: An FFP-free strategy in infants < 10 kg operated with CPB is technically feasible but results in an early post-CPB coagulopathy that was not completely compensated with our bleeding management protocol.

The Conundrum of Systemic Arterial Pressure Management on Cardiopulmonary Bypass.

The recently released EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass (CPB) in adult cardiac surgery [...].

The multifactorial dynamic perfusion index: A predictive tool of cardiac surgery associated acute kidney injury.

INTRODUCTION: cardiac surgery associated acute kidney injury (CSA-AKI) has a number of preoperative and intraoperative risk factors. Cardiopulmonary bypass (CPB) factors have not yet been elucidated in a single multivariate model. The aim of this study is to develop a dynamic predictive model for CSA-AKI. METHODS: retrospective study on 910 consecutive adult cardiac surgery patients. Baseline data were used to settle a preoperative CSA-AKI risk model (static risk model, SRM); CPB related data were assessed for association with CSA-AKI. CPB duration, nadir oxygen delivery, time of exposure to a low oxygen delivery, nadir mean arterial pressure, peak lactates and red blood cell transfusion were included in a multivariate dynamic perfusion risk (DPR). SRM and DPR were merged into a final logistic regression model (multifactorial dynamic perfusion index, MDPI). The three risk models were assessed for discrimination and calibration. RESULTS: the SRM model had an AUC of 0.696 (95% CI 0.663-0.727), the DPR model of 0.723 (95% CI 0.691-0.753), and the MDPI model an AUC of 0.769 (95% CI 0.739-0.798). The difference in AUC between SRM and DPR was not significant (p = 0.495) whereas the AUC of MDPI was significantly larger than that of SRM (p = 0.004) and DPR (p = 0.015). CONCLUSIONS: inclusion of dynamic indices of the quality of CPB improves the discrimination and calibration of the preoperative risk scores. The MDPI has better predictive ability than the existing static risk models and is a promising tool to integrate different factors into an advanced concept of goal-directed perfusion.

Bleeding and Thrombotic Issues during Extracorporeal Membrane Oxygenation.

Extracorporeal Membrane Oxygenation (ECMO) is an advanced life support modality for patients with respiratory or cardiac failure refractory to standard therapy [...].

Influence of left ventricular unloading on pediatric post-cardiotomy veno-arterial extracorporeal life support outcomes.

Background: The effectiveness of veno-arterial extracorporeal life support (V-A ECLS) in treating neonatal and pediatric patients with complex congenital heart disease (CHD) and requiring cardio-circulatory assistance is well-known. Nevertheless, the influence of left ventricle (LV) distension and its countermeasure, namely LV unloading, on survival and clinical outcomes in neonates and children treated with V-A ECLS needs still to be addressed. Therefore, the aim of this study was to determine the effects of LV unloading on in-hospital survival and complications in neonates and children treated with V-A ECLS. Methods: The clinical outcomes of 90 pediatric patients with CHD under 16 years of age supported with V-A ECLS for post-cardiotomy cardiogenic shock (CS) were retrospectively reviewed in relationship with the presence or absence of an active LV unloading strategy. Results: The patient cohort included 90 patients (age 19.6 ± 31.54 months, 64.4% males), 42 of whom were vented with different techniques (38 with atrial septostomy (AS) or left atria cannula, two with cannula from LV apex, 1 with intra-aortic balloon pump (IABP), and one with pigtail across the aortic valve). The LV unloading strategy significantly increased the in-hospital survival (odds ratio [OR] = 2.74, 95% CI 1.06-7.08; p = 0.037). On the contrary, extracorporeal cardiopulmonary resuscitation decreased the related survival (OR = 0.32, 95% CI 1.09-0.96; p = 0.041). The most common complications were infections (28.8%), neurological injury (26%), and bleeding (25.6%). However, these did not differently occur in venting and no-venting groups. Conclusion: In pediatric patients with CHD supported with V-A ECLS for post-cardiotomy CS, the LV unloading strategy was associated with increased survival.

Predictors of Neurological Complications of Pediatric Post-Cardiotomy Extracorporeal Life Support.

Background: Post-cardiotomy extracorporeal membrane oxygenation (ECMO) was associated with significant neurological complications affecting the overall outcome. The aim of the work is to determine the incidence and the predictors of neurological events during pediatric extracorporeal life support after cardiac surgery. Patients & Methods: This is a retrospective study that encompassed all neonates, infants, and children (<18 years of age) who need extracorporeal life support following cardiac surgery between January 2015 and December 2018 at San Donato Hospital, Italy. Data as regards surgical procedure of congenital heart disease, in-hospital mortality, length of ECMO, hospital stay durations, short-term neurological ECMO complications and outcome were analyzed. Results: The sixty-three patients who received post-cardiotomy ECMO, Neurological complications were evident in 31.7% in the form of ischemic stroke in 17.5% and hemorrhagic stroke in 11.1%. By multivariable analysis, the older age of cyanotic cases, the need for a venting cannula, and the rapid CO2 drop in the first 24 h were the most independent risk factors for neurological complications. Prolonged ECMO support and hospital stay duration were associated with neurological sequelae. Conclusion: Neurological complications either ischemic or hemorrhagic strokes were common during pediatric post-cardiotomy ECMO and were significantly related to prolonged ECMO support and hospital stay. Predictors of these neurological sequelae are the older cyanotic cases, the need for a venting cannula, the oxygenator thrombosis, and the rapid CO2 drop in the first 24 h of ECMO.

Atrial Septostomy for Left Ventricular Unloading During Extracorporeal Membrane Oxygenation for Cardiogenic Shock: Animal Model.

OBJECTIVES: The aim of this study was to quantify and understand the unloading effect of percutaneous balloon atrial septostomy (BAS) in acute cardiogenic shock (CS) treated with venoarterial (VA) extracorporeal membranous oxygenation (ECMO). BACKGROUND: In CS treated with VA ECMO, increased left ventricular (LV) afterload is observed that commonly interferes with myocardial recovery or even promotes further LV deterioration. Several techniques for LV unloading exist, but the optimal strategy and the actual extent of such procedures have not been fully disclosed. METHODS: In a porcine model (n = 11; weight 56 kg [53-58 kg]), CS was induced by coronary artery balloon occlusion (57 minutes [53-64 minutes]). Then, a step-up VA ECMO protocol (40-80 mL/kg/min) was run before and after percutaneous BAS was performed. LV pressure-volume loops and multiple hemoglobin saturation data were evaluated. The Wilcoxon rank sum test was used to assess individual variable differences. RESULTS: Immediately after BAS while on VA ECMO support, LV work decreased significantly: pressure-volume area, end-diastolic pressure, and stroke volume to ∼78% and end-systolic pressure to ∼86%, while superior vena cava and tissue oximetry did not change. During elevating VA ECMO support (40-80 mL/kg/min) with BAS vs without BAS, we observed 1) significantly less mechanical work increase (122% vs 172%); 2) no end-diastolic volume increase (100% vs 111%); and 3) a considerable increase in end-systolic pressure (134% vs 144%). CONCLUSIONS: In acute CS supported by VA ECMO, atrial septostomy is an effective LV unloading tool. LV pressure is a key component of LV work load, so whenever LV work reduction is a priority, arterial pressure should carefully be titrated low while maintaining organ perfusion.

Anti-Factor Xa-Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions.

Choices for monitoring of unfractionated heparin (UFH) anticoagulation in extracorporeal membrane oxygenation (ECMO) patients include activated clotting time, activated partial thromboplastin time, reaction times of viscoelastic tests, and anti-factor Xa activity (between 0.3 and 0.7 IU/mL). Recent studies propose the anti-factor Xa to be the gold standard for monitoring UFH anticoagulation in ECMO. However, many extraneous factors combined question the utility of anti-factor Xa as the sole method of monitoring of UFH effects in ECMO. Anti-factor Xa is a chromogenic assay, which may be biased by the frequently elevated values of bilirubin and free hemoglobin in ECMO patients. The test may alternatively underestimate UFH effects in cases of low antithrombin values. More importantly, the anti-factor Xa assay is a plasma-based test which does not take into account the role of platelets and fibrinogen in forming a stable clot. Thrombocytopenia and platelet dysfunction are common features in ECMO patients, and underestimating their role may lead to over-anticoagulation, should only anti-factor Xa guiding be used to adjust the UFH dose. Conversely, fibrinogen is an acute phase protein, and some patients may experience high levels of fibrinogen during the ECMO course. In this case, an UFH monitoring based on anti-factor Xa is insensitive to this condition, although it may potentially be associated with thrombotic complications. Finally, the generally suggested range of 0.3 to 0.7 IU/mL is a somewhat arbitrary estimate, based on the desired range for treating and preventing thrombotic events in non-ECMO patients. In conclusion, anti-factor Xa may offer useful information on the real effects of UFH only when combined with a whole blood test capable of assessing the relative contribution of platelets and fibrinogen to clot formation.

Fibrinogen levels and postoperative chest drain blood loss in low-weight (<10 kg) children undergoing cardiac surgery.

INTRODUCTION: Low-weight (<10 kg) children undergoing cardiac surgery with cardiopulmonary bypass are prone to dilution and consumption of soluble coagulation factors and fibrinogen. Low levels of fibrinogen may represent a possible cause of severe postoperative chest drain blood loss. The present study investigates the association between post-cardiopulmonary bypass fibrinogen levels and postoperative chest drain blood loss and severe bleeding, aiming to identify possible cut-off values to trigger specific interventions. METHODS: Prospective cohort study on 77 patients weighing <10 kg undergoing cardiac surgery with cardiopulmonary bypass. Haemostasis and coagulation data were collected before surgery (standard tests and thromboelastometry), after protamine (thromboelastometry) and at the arrival in the intensive care unit (standard tests). The primary outcome variable was severe bleeding (chest drain blood loss >30 ml kg-1/24h). RESULTS: Factors being independently associated with severe bleeding were the international normalized ratio and the fibrinogen levels at the arrival in the intensive care unit. Once corrected for other confounders, fibrinogen levels had an odds ratio of 0.2 (95% confidence interval = 0.011-0.54) per 1 gL-1 for severe bleeding. The discrimination power was fair (area under the curve = 0.770). The best cut-off value was identified at a fibrinogen level of 150 mg dL-1, with a sensitivity of 52%, a specificity of 85% and a positive predictive value of 60% for severe bleeding. CONCLUSION: Both a prolonged international normalized ratio and low fibrinogen levels were predictive for severe bleeding, underscoring the role of coagulation factors dilution and consumption in this specific patient population.

Bloodstream infections during post-cardiotomy extracorporeal membrane oxygenation: Incidence, risk factors, and outcomes.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation after heart surgery is a relatively common procedure. It is easily applicable but associated with a number of complications, including bloodstream infections. The aim of this study is to determine the current rate and the risk factors related to bloodstream infections acquired during post-cardiotomy veno-arterial extracorporeal membrane oxygenation. METHODS: Single-center retrospective study. From the overall population receiving any kind of extracorporeal membrane oxygenation from March 2013 through December 2017, the post-cardiotomy patient population was extracted, with a final sample of 92 veno-arterial extracorporeal membrane oxygenations. The risk of developing bloodstream infections as a function of extracorporeal membrane oxygenation exposure was analyzed with appropriate statistical analyses, including a Kaplan-Meier analysis. RESULTS: Overall, 14 (15.2%) patients developed a bloodstream infection during extracorporeal membrane oxygenation or within the first 48 h after extracorporeal membrane oxygenation removal. The total extracorporeal membrane oxygenation duration in the population was 567 days, and the incidence of bloodstream infections was 24.7 bloodstream infections/1000 extracorporeal membrane oxygenation days. There was a progressive increase in the cumulative hazard ratio during the first 7 days, reaching a value of 20% on day 7; from day 7 and day 15, the hazard ratio remained stable, with a second increase after day 15. The independent risk factors associated with bloodstream infections were adult age, pre-implantation serum total bilirubin level, and the amount of chest drain blood loss. DISCUSSION: Infections acquired during veno-arterial extracorporeal membrane oxygenation are common. Identify the risk factors that may improve strategies for treatment and prevention.

The combined effects of the microcirculatory status and cardiopulmonary bypass on platelet count and function during cardiac surgery.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass is associated with important changes in the microcirculation, usually attributed to endothelial dysfunction. Another common finding of cardiac surgery is postoperative thrombocytopenia and platelet loss of function. OBJECTIVE: To investigate the association between microvascular flow pattern and postoperative changes in platelet count and function in cardiac surgery patients. METHODS: Twelve adult cardiac surgery patients received microvascular circulation (sidestream darkfield sublingual mucosa analysis) and platelet count and function (multiple electrode aggregometry ADPtest and TRAPtest) assessment before and after cardiopulmonary bypass. RESULTS: After cardiopulmonary bypass, sublingual microcirculation showed a significantly (P = 0.001) decreased microvascular flow index and increased heterogeneity index (P = 0.006). Platelet function significantly decrease after cardiopulmonary bypass both at ADPtest (P = 0.011) and TRAPtest (P = 0.002). Preoperative patterns of poor microvascular perfusion (low perfused vessels density and total vessels density) were significantly associated with lower values of post-cardiopulmonary bypass platelet function (ADPtest, P = 0.009, TRAPtest, P = 0.031) and count (P = 0.048). CONCLUSIONS: A preoperative disturbance of the microcirculation is associated with a greater postoperative platelet dysfunction. Endothelial damage, chemical and mechanical stimuli are the possible link between the two patterns.

Severe Pneumonia Caused by Influenza A (H1N1) Virus Successfully Managed with Extracorporeal Life Support in a Comorbid Former Preterm Infant.

Influenza A (H1N1) virus infection is a global health burden, leading to significant pediatric morbidity and mortality. Prematurity, young age and comorbidities are important risk factors for unfavorable outcomes. Preventive strategies, such as healthcare workers and household contacts vaccination as well as the implementation of infection control practices during the epidemic season, are crucial to protect the most vulnerable populations. Early diagnosis, timely administration of antiviral drugs and supportive therapy are crucial to lead to a complete recovery. When conventional treatment fails, extracorporeal life support (ECLS) may be employed. In neonates and young infants, this high-tech support is burdened by specific technical complexity. Despite the potential risks related to this aggressive approach, ECLS is a life-saving procedure in 65% of pediatric viral pneumonia and in 73% of sepsis cases. Here, we report the successful outcome of a 51-day formerly preterm infant, suffering from a surgical necrotizing enterocolitis (NEC), complicated with hospital-acquired pneumonia due to influenza A (H1N1) virus. She developed a severe respiratory failure, unresponsive to conventional therapy, and successfully treated with ECLS. To our knowledge, this is the first report on the use of ECLS in a formerly preterm infant, suffering from NEC complicated by influenza A (H1N1) virus infection.

Carbon dioxide production during cardiopulmonary bypass: pathophysiology, measure and clinical relevance.

Carbon dioxide production during cardiopulmonary bypass derives from both the aerobic metabolism and the buffering of lactic acid produced by tissues under anaerobic conditions. Therefore, carbon dioxide removal monitoring is an important measure of the adequacy of perfusion and oxygen delivery. However, routine monitoring of carbon dioxide removal is not widely applied. The present article reviews the main physiological and pathophysiological sources of carbon dioxide, the available techniques to assess carbon dioxide production and removal and the clinically relevant applications of carbon dioxide-related variables as markers of the adequacy of perfusion during cardiopulmonary bypass.

Coagulation monitoring in postcardiotomy ECMO: conventional tests, point-of-care, or both?

BACKGROUND: The aim of this study was to assess the association of the coagulation point-of-care (POC) tests activated clotting time (ACT) and thromboelastography-derived parameters reaction time (R-time) and maximum amplitude (MA) with the standard coagulation tests during postcardiotomy extracorporeal membrane oxygenation (ECMO), finding adequate values predictive for the target range of the standard coagulation tests. METHODS: Thirty-one patients undergoing postcardiotomy ECMO with heparin anticoagulation were analyzed. Paired data of the POC tests and standard coagulation tests were analyzed for association and positive predictive value (PPV). RESULTS: The following target range values for standard coagulation test were settled: activated partial thromboplastin time (aPTT) 50-70 seconds; international normalized ratio (INR) 1.5-2.5; platelet count >50,000 cells/µL; fibrinogen >150 mg/dL. The best predictor for the desired aPTT range was an ACT of 162-185 seconds. A combination of an ACT<162 seconds with an R-time <10 minutes had an 83% PPV for a short aPTT. A combination of an ACT>185 seconds with an R-time >27 minutes had a 71% PPV for a long aPTT. No predictive ability of the POC tests was found in terms of the optimal INR range. An MA value <41 mm had a 75% PPV for a low platelet count or fibrinogen level. CONCLUSIONS: Diagnostic-therapeutic algorithms based on coagulation POC-tests may be useful to manage anticoagulation during postcardiotomy ECMO. The best PPV for prompting therapeutic decision is provided by a combination of ACT and visco-elastic tests.

Modern ECMO: why an ECMO programme in a tertiary care hospital.

Extracorporeal Membrane Oxygenation (ECMO) represents a useful tool to support the lungs and the heart when all conventional therapies failed and the patients are at risk of death. While the Extracorporeal Life Support Organization (ELSO) collects data from different institutions that joined the Registry and reports overall outcome, individual centres often collide with results below expectations, either in adults and in paediatric population. Some authors suggest that poor outcomes could be overcome with a programme dedicated to ECMO, with specialized professionals adequately trained on ECMO and with a consistent number of procedures. In 2012, The IRCCS PSD ECMO Programme was instituted with the specific aim of achieving better results than hitherto obtained. After only 1 year of activity, the results justified the programme, with a better survival rate for each group investigated, particularly in adults, but surprisingly in paediatrics too, where the results were better than what reported by ELSO. Although the number of patients treated with ECMO is still growing up, the effects of the ECMO programme continue to exert a positive action on outcome even now. The present article reports data on survival, blood loss, and blood consumption during ECMO in the last few years at our institution.

Hemodilution on cardiopulmonary bypass as a determinant of early postoperative hyperlactatemia.

OBJECTIVE: The nadir hematocrit (HCT) on cardiopulmonary bypass (CPB) is a recognized independent risk factor for major morbidity and mortality in cardiac surgery. The main interpretation is that low levels of HCT on CPB result in a poor oxygen delivery and dysoxia of end organs. Hyperlactatemia (HL) is a marker of dysoxic metabolism, and is associated with bad outcomes in cardiac surgery. This study explores the relationship between nadir HCT on CPB and early postoperative HL. DESIGN: Retrospective study on 3,851 consecutive patients. MEASUREMENTS AND MAIN RESULTS: Nadir HCT on CPB and other potential confounders were explored for association with blood lactate levels at the arrival in the Intensive Care Unit (ICU), and with the presence of moderate (2.1 - 6.0 mMol/L) or severe (> 6.0 mMol/L) HL. Nadir HCT on CPB demonstrated a significant negative association with blood lactate levels at the arrival in the ICU. After adjustment for the other confounders, the nadir HCT on CPB remained independently associated with moderate (odds ratio 0.96, 95% confidence interval 0.94-0.99) and severe HL (odds ratio 0.91, 95% confidence interval 0.86-0.97). Moderate and severe HL were significantly associated with increased morbidity and mortality. CONCLUSIONS: Hemodilution on CPB is an independent determinant of HL. This association, more evident for severe HL, strengthens the hypothesis that a poor oxygen delivery on CPB with consequent organ ischemia is the mechanism leading to hemodilution-associated bad outcomes.

Heparin-like effect in postcardiotomy extracorporeal membrane oxygenation patients.

INTRODUCTION: Unfractionated heparin (UFH) is the anticoagulant of choice for extracorporeal membrane oxygenation (ECMO), but bivalirudin can be used as an alternative. The purpose of the present study is to investigate the existence of a heparin-like effect (HLE) during heparin-free ECMO. METHODS: This is a retrospective study on patients treated with ECMO and receiving bivalirudin as the sole anticoagulant. Thromboelastography (TEG) tests with and without heparinase were recorded during the ECMO duration. A total of 41 patients (22 pediatrics and 19 adults) treated with ECMO after cardiac surgery procedures and receiving only bivalirudin-based anticoagulation were studied. Based on the presence of a different reaction time (R-time) between the TEG test with heparinase or without heparinase we defined the presence of a HLE. Survival to hospital discharge, liver failure, sepsis, bleeding and transfusion rate were analyzed for association with HLE with univariate tests. RESULTS: HLE was detected in 56.1% of the patients. R-times were significantly shorter in tests done with heparinase versus without heparinase during the first seven days on ECMO. Patients with HLE had a significantly (P = 0.046) higher rate of sepsis (30%) than patients without HLE (5.6%) at a Pearson's chi-square test. CONCLUSIONS: A heparin-like effect is common during ECMO, and most likely due to a release of heparinoids from the glycocalyx and the mast cells, as a consequence of sepsis or of the systemic inflammatory reaction triggered by the contact of blood with foreign surfaces.