Filip De Somer

O2 delivery and CO2 production during cardiopulmonary bypass as determinants of acute kidney injury: time for a goal-directed perfusion management?

IntroductionAcute kidney injury (AKI) is common after cardiac operations. There are different risk factors or determinants of AKI, and some are related to cardiopulmonary bypass (CPB). In this study, we explored the association between metabolic parameters (oxygen delivery (DO2) and carbon dioxide production (VCO2)) during CPB with postoperative AKI.MethodsWe conducted a retrospective analysis of prospectively collected data at two different institutions. The study population included 359 adult patients. The DO2 and VCO2 levels of each patient were monitored during CPB. Outcome variables were related to kidney function (peak postoperative serum creatinine increase and AKI stage 1 or 2). The experimental hypothesis was that nadir DO2 values and nadir DO2/VCO2 ratios during CPB would be independent predictors of AKI. Multivariable logistic regression models were built to detect the independent predictors of AKI and any kind of kidney function damage.ResultsA nadir DO2 level < 262 mL/minute/m2 and a nadir DO2/VCO2 ratio < 5.3 were independently associated with AKI within a model including EuroSCORE and CPB duration. Patients with nadir DO2 levels and nadir DO2/VCO2 ratios below the identified cutoff values during CPB had a significantly higher rate of AKI stage 2 (odds ratios 3.1 and 2.9, respectively). The negative predictive power of both variables exceeded 90%. The most accurate predictor of AKI stage 2 postoperative status was the nadir DO2 level.ConclusionsThe nadir DO2 level during CPB is independently associated with postoperative AKI. The measurement of VCO2-related variables does not add accuracy to the AKI prediction. Since DO2 during CPB is a modifiable factor (through pump flow adjustments), this study generates the hypothesis that goal-directed perfusion management aimed at maintaining the DO2 level above the identified critical value might limit the incidence of postoperative AKI.

Safety and Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with High-Dose Oxaliplatin in Patients with Peritoneal Carcinomatosis

BackgroundCytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC) has an established role in selected patients with peritoneal carcinomatosis (PC). We analyzed the safety and efficacy of HIPEC using high-dose oxaliplatin, a cytotoxic agent commonly used in metastatic colorectal cancer and showing promising activity in ovarian cancer and mesothelioma.MethodsFollowing complete cytoreduction, HIPEC was performed using 460 mg/m2 oxaliplatin in 5% dextrose for 30 min at a temperature of 41–42°C. Open perfusion (coliseum technique) was performed in all patients. Metabolic, electrolyte, and hemodynamic changes were recorded during chemoperfusion as well as postoperative morbidity, mortality, late toxicity, and survival.ResultsFrom July 2005 to January 2007, 52 patients were treated. Chemoperfusion with 5% dextrose resulted in temporary significant hyperglycemia, hyponatremia, and metabolic acidosis. Major morbidity developed in 24% of patients, while 30-day mortality did not occur. One patient developed unexplained repeated episodes of hemoperitoneum. Chemoperfusion with oxaliplatin resulted in mild hepatic toxicity evidenced by persistent elevation of glutamyl transferase and alkaline phosphatase 1 month after surgery. After a mean follow-up time of 14.5 months, nine patients died from disease progression. In colorectal cancer patients, actuarial overall survival was 80% at 1 year.ConclusionCytoreduction with HIPEC using high-dose oxaliplatin leads to manageable metabolic and electrolyte disturbances and frequent mild hepatic toxicity without discernible impact on postoperative morbidity. Longer follow-up in a larger patient cohort will be required to assess the real risk of unexplained hemoperitoneum observed in one patient, and to establish the long-term effect on local relapse and survival.

Acute and critically ill peripartum cardiomyopathy and 'bridge to' therapeutic options: a single center experience with intra-aortic balloon pump, extra corporeal membrane oxygenation and continuous-flow left ventricular assist devices

IntroductionPeripartum cardiomyopathy (PPCM) patients refractory to medical therapy and intra-aortic balloon pump (IABP) counterpulsation or in whom weaning from these therapies is impossible, are candidates for a left ventricular assist device (LVAD) as a bridge to recovery or transplant. Continuous-flow LVADs are smaller, have a better long-term durability and are associated with better outcomes. Extra corporeal membrane oxygenation (ECMO) can be used as a temporary support in patients with refractory cardiogenic shock. The aim of this study was to evaluate the efficacy and safety of mechanical support in acute and critically ill PPCM patients.MethodsThis was a retrospective search of the patient database of the Ghent University hospital (2000 to 2010).ResultsSix PPCM-patients were treated with mechanical support. Three patients presented in the postpartum period and three patients at the end of pregnancy. All were treated with IABP, the duration of IABP support ranged from 1 to 13 days. An ECMO was inserted in one patient who presented with cardiogenic shock, multiple organ dysfunction syndrome and a stillborn baby. Two patients showed partial recovery and could be weaned off the IABP. Four patients were implanted with a continuous-flow LVAD (HeartMate II®, Thoratec Inc.), including the ECMO-patient. Three LVAD patients were successfully transplanted 78, 126 and 360 days after LVAD implant; one patient is still on the transplant waiting list. We observed one peripheral thrombotic complication due to IABP and five early bleeding complications in three LVAD patients. One patient died suddenly two years after transplantation.ConclusionsIn PPCM with refractory heart failure IABP was safe and efficient as a bridge to recovery or as a bridge to LVAD. ECMO provided temporary support as a bridge to LVAD, while the newer continuous-flow LVADs offered a safe bridge to transplant.

Consensus statement: minimal criteria for reporting the systemic inflammatory response to cardiopulmonary bypass.

The lack of established cause and effect between putative mediators of inflammation and adverse clinical outcomes has been responsible for many failed anti-inflammatory interventions in cardiopulmonary bypass (CPB). Candidate interventions that impress in preclinical trials by suppressing a given inflammation marker might fail at the clinical trial stage because the marker of interest is not linked causally to an adverse outcome. Alternatively, there exist examples in which pharmaceutical agents or other interventions improve clinical outcomes but for which we are uncertain of any antiinflammatory mechanism. The Outcomes consensus panel made 3 recommendations in 2009 for the conduct of clinical trials focused on the systemic inflammatory response. This panel was tasked with updating, as well as simplifying, a previous consensus statement. The present recommendations for investigators are the following: (1) Measure at least 1 inflammation marker, defined in broad terms; (2) measure at least 1clinical end point, drawn from a list of practical yet clinically meaningful end points suggested by the consensus panel; and(3) report a core set of CPB and perfusion criteria that maybe linked to outcomes. Our collective belief is that adhering to these simple consensus recommendations will help define the influence of CPB practice on the systemic inflammatory response, advance our understanding of causal inflammatory mechanisms, and standardize the reporting of research findings in the peer-reviewed literature.

Mass transfer characteristics of artificial lungs.

An artificial lung is used during cardiopulmonary bypass to oxygenate blood and control blood temperature. The oxygen transfer rate-flow rate characteristics of three hollow fiber membrane artificial lungs (Sarns Turbo 440, Cobe Optima, Dideco Compactflo) were determined in vitro to characterize design features. Results are presented as a unique dimensionless relationship between Sherwood number, NSh (ratio of convective to diffusive mass transfer), Schmidt number, NSc (ratio of momentum to diffusive transport), and Reynolds number, NRe (ratio of inertial to viscous forces). This relationship is a function of device porosity, ϵ, and characteristic device length, &xgr;, defined as the ratio of the mean blood path and manifold length:MATHwhere &phgr; = 0.26 and m = 1.00 for NPe < 3,200 and &phgr; = 0.47 and m = 0.64 for NPe > 3,200 where NPe is the dimensionless Péclet number defined as NRe · NSc. We found good correspondence between the model predictions and in vitro blood oxygen transfer rates. We conclude that this dimensionless approach allows us (1) to compare artificial lungs independently, (2) to relate water tests to blood, and (3) to predict the oxygen transfer rate of a new artificial lung design.

The effect of retrograde autologous priming volume on haemodilution and transfusion requirements during cardiac surgery

OBJECTIVES Many cardiac procedures using cardiopulmonary bypass (CPB) still require intraoperative transfusion. Retrograde autologous priming (RAP) has been introduced to decrease haemodilution and the blood transfusion rate. This study is designed to determine the influence or RAP on intraoperative haematocrit, transfusion and its clinical consequences. METHODS The RAP effect was retrospectively studied in 753 patients during contemporary cardiac surgery, targeting a haematocrit of 25%. Multivariate linear regression analysis was performed to identify the independent factors influencing intraoperative haematocrit, transfusion rate and transfusion quantity. RESULTS RAP was used in 498 patients and compared with 255 controls. RAP decreased the haemodilution level (nadir haematocrit 26.8 standard deviation [SD] 4.0% in RAP vs 25.8 SD 3.6% in controls; P = 0.001) and transfusion frequency (26.1 vs 33.3%, P = 0.04), despite smaller patients (body surface area [BSA] 1.86 SD 0.20 m(2) vs 1.91 SD 0.21 m(2) in RAP vs controls; P = 0.002) with lower preoperative haematocrit (38.9 SD 4.4% vs 40.5 SD 4.6%; P < 0.001). Optimal RAP volume was overall 475 ml (ROC area 0.55; 95% confidence interval [CI] 0.50-0.60; P = 0.04) and 375 ml in patients with BSA <1.7 m(2) (ROC area 0.63; 95% CI 0.54-0.73; P = 0.008) to decrease the transfusion incidence. Multivariate analysis revealed RAP volume as a significant determinant of nadir haematocrit (β = 0.003, 95% CI 0.002-0.004, P < 0.001) and transfusion rate (odds ratio (OR) = 0.997, 95% CI 0.996-0.999, P < 0.001), independent of BSA, gender and preoperative haematocrit. CONCLUSIONS Retrograde autologous priming is an effective adjunct to decrease the blood transfusion rate, coping with the CPB-related haemodilution and its adverse clinical effects. A RAP volume individualized to each patient offers most benefit as part of a multidisciplinary blood conservation approach.

Decellularization of Heart Valve Matrices: Search for the Ideal Balance

Abstract: Objective: Currently used decellularization procedures have negative effects on extracellular matrix (ECM) integrity. The objective of this study is to evaluate four decellularization methods and their effect on the collagen ultrastructure, mechanical behavior and antigenicity of porcine aortic valves. Methods: Aortic valves were placed in a trypsin, osmotic, trypsin-osmotic or detergent-osmotic solution. Leaflets were processed for histology and mechanical testing. Matrices were implanted subdermally in rats to evaluate immune reaction and calcification. Results: Trypsin-osmotic methodology effected near-complete decellularization. Trypsin treatment resulted in cell removal only in the spongiosa layer. Osmotic and detergent-osmotic treatments did not remove any cells from the cusps. Mechanical strength was significantly inferior in the trypsin (p50,03) and trypsin-osmotic treated group (p50,04). Trypsin and trypsin-osmotic decellularized matrices evoked a strong CD31 inflammatory cell infiltration. Conclusion: Enzymatic-osmotic decellularization appears to be the only effective method to remove cellular components. However, the near cell free scaffolds still evokes a strong CD31 T-cell inflammatory reaction.

Acute and chronic effects of dysfunction of right ventricular outflow tract components on right ventricular performance in a porcine model: implications for primary repair of tetralogy of fallot

OBJECTIVES This study investigates the contribution of infundibular versus pulmonary valve (PV) dysfunction on right ventricular (RV) function in a porcine model. BACKGROUND Clinical outcome after repair of tetralogy of Fallot is determined by the adaptation of the right ventricle to the physiological sequelae of the right ventricular outflow tract (RVOT) reconstruction. Recent surgical techniques are pursuing a PV-versus infundibulum-sparing approach. METHODS In a porcine model, 3 types of RVOT dysfunction were created and compared with sham-operated controls: infundibular dysfunction (INF), PV insufficiency (PI), and combined infundibular-PV dysfunction (TAP). Both acute and chronic effects on RV function were studied by using conductance technology and magnetic resonance imaging. RESULTS In animals with PI, pulmonary regurgitant fraction progressed more in the presence of concomitant INF (54% in TAP versus 14% in PI; p = 0.03). Subsequently, RV end-systolic and end-diastolic volume increased more in both groups, resulting in decreased ejection fraction after 3 months. Preload-independent systolic indices showed acute impairment of RV contractility in all treatment groups but most in animals with infundibular scarring (INF and TAP). Further chronic deterioration was observed in animals of the TAP group. RV compliance improved proportionally most in the PI and TAP groups in relation to the extent of RV dilation. CONCLUSIONS Surgical RVOT dysfunction, whether it includes the infundibulum and/or the PV, has an immediate effect on RV performance. Although impaired RV contractility is due to intrinsic myocardial damage by infundibular distortion, it is chronically furthered by PI-related RV dilation. These findings support the adoption of a RVOT-sparing strategy to treat tetralogy of Fallot.

Hydrodynamic characteristics of artificial lungs.

An artificial lung is used during cardiopulmonary bypass to oxygenate blood and to control blood temperature. The pressure drop–flow rate characteristics of the membrane compartment in three hollow fiber membrane oxygenators were determined in vitro to characterize design features. Results are presented in a unique dimensionless relationship between Euler number, NEu (ratio of pressure drop to kinetic energy), and Reynolds number, NRe (ratio of inertial to viscous forces), and are a function of the device porosity, &egr;, and a characteristic device length, &xgr;, defined as the ratio of the mean blood path and manifold length:MATH This dimensionless approach allows us (1) to compare oxygenators independently, and (2) to relate water tests to blood.

Flexural mechanical properties of porcine aortic heart valve leaflets

Freshly excised porcine aortic heart valve cusps were subjected to a uni-axial flexural indentation test, from which the rupture characteristics and a functional stiffness parameter were determined. It was found that the flexural mechanical properties of aortic valve cusps (i) are unaffected by their coronary position and (ii) are sensitive to the effect of mechanical preconditioning. The resulting values of the cusps flexural mechanical properties are intended as a set of reference properties which scaffolds, meant for the tissue engineering of heart valves, must approximate in order to be considered as a functional replacement.