Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial.

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation). Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease. Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021. Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685). Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels. Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups. Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery. Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392.

The Efficacy of Resin Hemoperfusion Cartridge on Inflammatory Responses during Adult Cardiopulmonary Bypass.

AIM: This study aimed to evaluate the efficacy of the resin hemoperfusion device (HA380 hemoperfusion cartridge) on inflammatory responses during adult cardiopulmonary bypass (CPB). METHODS: Sixty patients undergoing surgical valve replacement were randomized into the HP group (n = 30) with an HA380 hemoperfusion cartridge in the CPB circuit or the control group (n = 30) with the conventional CPB circuit. The results of routine blood tests, blood biochemical indexes, and inflammatory factors were analyzed at V0 (pre-CPB), V1 (CPB 30 min), V2 (ICU 0 h), V3 (ICU 6 h), and V4 (ICU 24 h). RESULTS: The HP group had significantly lower levels of IL-6, IL-8, and IL-10. Significant estimation of group differences in the generalized estimating equation (GEE) models was also observed in IL-6 and IL-10. The HP group had significantly lower levels of creatinine (Cr), aminotransferase (AST), and total bilirubin (TBil) compared to the control group. The estimation of differences of Cr, AST, and TBil all reached statistical significance in GEE results. The HP group had significantly less vasopressor requirement and shorter mechanical ventilation time and ICU stay time as compared to the control group. CONCLUSION: The HA380 hemoperfusion cartridge could effectively reduce the systemic inflammatory responses and improve postoperative recovery of patients during adult CPB.

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation.

Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.

Development of a real-time blood damage monitoring device for cardiopulmonary bypass system using near-infrared spectroscopy.

The optical properties of hemoglobin could indicate the degree of hemolysis. We aimed to utilize this to develop a real-time blood damage monitoring device for cardiopulmonary bypass (CPB) systems. The real-time blood damage monitoring device comprised a near-infrared spectroscopy optical module with a fiber spectrometer and monitoring platform and computer software developed using LabVIEW 2017. The fiber spectrometer operated at wavelengths of 545, 660, and 940 nm and contained a detector fiber bundle (source-detector distance = 1.0-2.5 cm). CPB operation was simulated using an artificial heart-lung machine with a flow rate of 3, 4, or 5 L/min. Four hundred milliliter of anticoagulated porcine blood was continuously rotated for 4 h. The transmittance, reflectivity, and absorbance of the blood were measured using the optical device at a frequency of 25 Hz and then digitally averaged into 1-s interval. Samples of damaged blood were collected at regular intervals for in vitro hemolysis tests to calculate the normalized index of hemolysis (NIH). All experiments were repeated three times. We prepared 28 blood bags containing 400 ml of anticoagulant. Paired t test was used to examine the test-retest reliability of the differences between the three methods and control samples. Statistical tests revealed significant differences in the mean values between the test and control groups over time (P < 0.01). Relationship was established between the real-time monitoring results and the NIH values. An effective blood damage detection method that combined in vitro hemolysis tests and near-infrared spectroscopy was achieved. The results demonstrate the clinical potential of a real-time, low-cost, and reliable blood damage monitoring device to improve the safety of CPB operation.

Nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass in infants: A pilot randomized controlled trial.

Our objective was to assess the effect of nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) in infants on platelet count, platelet function, clinical outcomes, and safety. A randomized, double-blinded, placebo-controlled clinical trial in infants less than a year of age undergoing cardiac surgery requiring CPB was undertaken. Nitric oxide at a dose of 20 ppm was added to the sweep gas in the treatment group. Blood was collected at baseline and prior to separation from CPB to measure platelet count and function as determined by responsiveness to specific agonists. Clinical outcomes were observed through hospital discharge. Methemoglobin levels were measured preoperatively, at the conclusion of CPB, and upon admission to the ICU. Forty patients consented and were randomized in the trial. Eighteen patients were randomized to the treatment group and 22 were included in the placebo group. The groups were similar in terms of age, weight, gender, and surgical complexity. No significant differences were found in measures of platelet count, platelet response to agonist, or clinical outcomes. Patients in the treatment group had higher methemoglobin levels after receiving nitric oxide, but no levels approached toxicity (maximum 2.4%). Nitric oxide added to the sweep gas of the oxygenator during CPB in infants did not have an appreciable effect on the preservation of platelet count, platelet responsiveness to agonist, or clinical outcomes. Methemoglobin levels were increased after receiving nitric oxide but were far below a toxic level of 15%.

Development and accuracy evaluation of a degree of occlusion visualization system for roller pumps used in cardiopulmonary bypass.

In roller pumps used for cardiopulmonary bypass (CPB), the degree of blockage within the tube resulting from compression of the tube by the rollers, or the degree of occlusion, is closely related to hemolysis, with both tight occlusive and non-occlusive degrees promoting hemolysis. There are as yet no international standards regarding methods of adjusting occlusiveness, and the amount of mechanical stress exerted upon blood remains unknown. To prevent hemolysis during CPB using roller pumps, there is a need to clarify and quantitatively assess the mechanical stress of the occlusiveness of the roller pump. In this study, we have developed a degree of occlusion quantification system which constructs the flow channel shape within an occluded tube from red optical density images, and we have verified the validity of this system. Utilizing a linear actuator, an acrylic roller and raceway, a solution colored with simulated blood powder, and a 3/8-inch vinyl chloride tube, this system uses a camera to capture red optical density images within an occluded tube and constructs the tube flow channel shape using a formula manipulation system. To verify the accuracy of this system, we compared the thickness of a cross-section of the flow channel constructed with the degree of occlusion quantification system with the thickness of a cross-section of silicone cured under the same occlusion conditions. Our experiments indicated that for areas with a small tube gap, this system can construct highly accurate three-dimensional shapes and obtain quantitative indicators assessing the degree of occlusion.

The impact of roller pump-assisted cardiotomy suction unit on hemolysis.

Hemolysis in cardiac surgery is often related to the contact of blood with air or artificial surfaces. Variations of negative pressure in the suction cannulas may represent an additional factor. Limited data exist on the contribution of a roller pump-assisted (RPA) cardiotomy suction unit to hemolysis. Elevation of free hemoglobin (fHb) following air suction (AS) or suction tip occlusion (STO) events of a pump-assisted cardiotomy suction unit was investigated in a mock circuit filled with blood from slaughtered domestic pigs. AS-associated hemolysis was measured over 240 minutes with 2 minutes of AS occurring every 10 minutes. STO-associated hemolysis was analyzed over 80-minute periods: configuration 1 (c1) comprised a cycle of 20 minutes (min) occlusion and 60 minutes RPA flow (20/60 minutes); c2 comprised 20 cycles of 1/3 minutes; c3 comprised 40 cycles of 0.5/1.5 minutes; and c4 comprised 80 cycles of 0.25/0.75 minutes. The AS setup did not lead to significant hemolysis after 2 (P = .97), 3 (P = .40) or 4 (P = .11) hours. The STO setup showed the greatest hemolysis (ΔfHb of 30 mg/dL) in c1 after 20 minutes. ΔfHb was different in c1 from all other configurations at 20 minutes (P < .0001) and 80 minutes (P < .05). Ex vivo generation of large negative pressures by STO events is the main cause of cardiotomy suction-associated hemolysis. The clinical relevance of this mechanism needs further investigations.

Direct true lumen cannulation in type A acute aortic dissection: A review of an 11 years' experience.

OBJECTIVES: Direct true lumen cannulation (DTLC) of the aorta is an alternative cardiopulmonary bypass cannulation technique in the context of type A acute aortic dissection (A-AAD). DTLC has been reported to be effective in restoring adequate perfusion to jeopardized organs. This study reports and compares operative outcomes with DTLC or alternative cannulation techniques in a large cohort of patients with A-AAD. METHODS: All patients who underwent surgery for A-AAD between January 2006 and January 2017 in Mainz university hospital were reviewed. The choice of cannulation technique was left to the operating surgeon, however DTLC was our preference in patients who were in state of shock or showed signs of tamponade or hypoperfusion, in cases of potential cerebral malperfusion, as well as in patients who were under resuscitation. RESULTS: A total of 528 patients (63% males, mean age 64±13.8 years) underwent emergency surgery for A-AAD. The DTLC technique was used in 52.4% of patients. The DTLC group of patients had worse clinical status at the time of presentation with more shock, tamponade, true lumen collapse, cerebral and other malperfusion states. New neurologic events were diagnosed in around 8% of patients in each group following surgery, but there was a trend for quicker neurological recovery in the DTLC-group. Early mortality rates, short-term and long-term survival rates did not differ between the two groups. CONCLUSIONS: DTLC is a safe cannulation technique that enables effective antegrade true lumen perfusion in complicated A-AAD scenarios, and is an advantageous addition to the aortic surgeons' armamentarium.

Long-term results of endoclamping in patients undergoing minimally invasive mitral valve surgery where external aortic clamping cannot be used - a propensity matched analysis.

BACKGROUND: Minimally invasive mitral valve surgery is standard of care in many centres and it is commonly associated with the need for cardiopulmonary bypass. Conventional external aortic clamping (exoclamping) is not always feasible, so endoaortic clamping (endoclamping) has evolved as a viable alternative. The aim of this study is to compare endoclamping (Intraclude™, Edwards Lifesciences) with exoclamping (Chitwood) during minimally invasive mitral valve procedures. METHODS: This single-centre study included 822 consecutive patients undergoing minimally invasive mitral valve procedures. The endoclamp was used in 64 patients and the exoclamp in 758. Propensity-score (PS) matching was performed resulting in 63 patients per group. Outcome measures included procedural variables, length of intensive care unit (ICU) and hospital stay, major adverse cardiac and cerebrovascular events (MACCE) and repeat surgery. RESULTS: The mean age was similar in the two group (62.2 [endoclamp] vs. 63.5 [exoclamp] years; p = 0.554), as were the cardiopulmonary bypass (145 vs. 156 min; p = 0.707) and the procedure time (203 vs. 211 min; p = 0.648). The X-clamp time was significantly shorter in the endoclamp group (88 vs. 99 min; p = 0.042). Length of ICU stay (25.0 vs. 23.0 h) and length of hospital stay (10.0 vs. 9.0 days) were slightly longer in the endoclamp group, but without statistical significance. There were nominal but no statistically significant differences between the groups in the rates of stroke, vascular complications, myocardial infarction or repeat mitral valve surgery. The conversion rate to open sternotomy approach was 2.4% without difference between groups. The estimated 7-year survival rate was similar for both groups (89.9% [endoclamp]; 84.0% [exoclamp]) with a hazard ratio of 1.291 (95% CI 0.453-3.680). CONCLUSIONS: Endoaortic clamping is an appropriate and reasonably safe alternative to the conventional Chitwood exoclamp for patients in which the exoclamp cannot be used because the ascending aorta cannot be safely mobilised.

Cardiopulmonary bypass and internal thoracic artery: Can roller or centrifugal pumps change vascular reactivity of the graft? The IPITA study: A randomized controlled clinical trial.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response (SIRS) and affects the organ vascular bed. Experimentally, the lack of pulsatility alters myogenic tone of resistance arteries and increases the parietal inflammatory response. The purpose of this study was to compare the vascular reactivity of the internal thoracic arteries (ITAs) due to the inflammatory response between patients undergoing coronary artery bypass grafting (CABG) under CPB with a roller pump or with a centrifugal pump. METHODS: Eighty elective male patients undergoing CABG were selected using one or two internal thoracic arteries under CPB with a roller pump (RP group) or centrifugal pump (CFP group). ITA samples were collected before starting CPB (Time 1) and before the last coronary anastomosis during aortic cross clamping (Time 2). The primary endpoint was the endothelium-dependent relaxation of ITAs investigated using wire-myography. The secondary endpoint was the parietal inflammatory response of arteries defined by the measurements of superoxide levels, leukocytes and lymphocytes rate and gene expression of inflammatory proteins using. Terminal complement complex activation (SC5b-9) and neutrophil activation (elastase) analysis were performed on arterial blood at the same times. RESULTS: Exposure time of ITAs to the pump flow was respectively 43.3 minutes in the RP group and 45.7 minutes in the CFP group. Acetylcholine-dependent relaxation was conserved in the two groups whatever the time. Gene expression of C3 and C4a in the artery wall decreased from Time 1 to Time 2. No oxidative stress was observed in the graft. There was no difference between the groups concerning the leukocytes and lymphocytes rate. SC5b-9 and elastase increased between Time 1 and Time 2. CONCLUSION: Endothelium-dependent relaxation of the internal thoracic arteries was preserved during CPB whatever the type of pump used. The inflammatory response observed in the blood was not found in the graft wall within this time frame. TRIAL REGISTRATION: Name of trial study protocol: IPITA Registration number (ClinicalTrials.gov): NCT04168853.

Water condensation from gas outlet of oxygenator.

Condensation and water loss from gas output of the cardiopulmonary bypass (CPB) oxygenator has been the study object of several research. However, little is known about the propagation of the condensation formed at the level of oxygenator and how potentially it can contaminate the surrounding environment. We aimed to document the moment of formation of the 'gas steam' derived from the CPB oxygenator during cardiac surgery with thermography imaging. Thermographic camera is a device that creates an image using infrared radiation, similar to a common camera that forms an image using visible light. The brightest (warmest) parts of the image are customarily colored white, the intermediate temperatures reds and yellows, and the dimmest (coolest) parts black. Thermal image captures the condensation phenomenon around the oxygenator perimeter with the same color/temperature code (yellow) of gas outlet. The use of aspiration at the level of the gas outlet could also favor the elimination of the condensation, improve gas exchanges, and potentially reduce the spread of hazardous substances in the operating room.

Efficiency of Minimized Circuits of a Heart Roller Pump on Systemic Inflammatory Response Syndrome and Multiorgan Effects in a Rat Model.

BACKGROUND: The aim of this study is to compare the effects of tubing length on systemic inflammatory response syndrome and myocardial protection in a rat model of cardiopulmonary bypass (CPB) from a histological standpoint. METHODS: Twelve adult male Wistar Albino rats weighing >180 g were randomly selected and divided into 2 groups. In 1 group, the pump lines were kept 1 m shorter than standard. The right jugular vein and tail artery were cannulated using a 16-gauge catheter. Animals received 500 IU/kg intravenous heparin. Cardiac index and rectal temperature were set at 2.4 mL and 36°C, respectively. Total line volume was maintained at 8 mL. A roller pump was adjusted to supply a blood flow of 6 to 28 mL/min (mean 10 mL/min), similar to the typical cardiac output of rats. CPB duration was 15 minutes throughout the experiment. After sacrifice, tissue samples were collected from heart, liver, and kidney for histomorphologic examination. RESULTS: All histochemical and histomorphologic analyses, performed by 2 blinded researchers, revealed band loss in cardiomyocytes, mononuclear (MNL) cell infiltration, and impaired fibrillar organization in the standard-line group. Additionally in that group, sinusoidal dilatation in the liver, low-level congestion, focal necrosis, and periportal MNL infiltration were noted. In the shorter-line group, on the other hand, MNL cell infiltration, band loss in myofibrils, and cardiomyocyte degeneration were rarely observed. Higher liver congestion and lower MNL cell infiltration were observed in the shorter-line group. No significant differences were found in kidney samples. CONCLUSION: In a shorter-line roller pump test model, less multiorgan damage and fewer systemic inflammatory responses were observed. It may be applicable to keep CPB lines as close to the table as possible, especially in pediatric cardiac surgery cases.

The effect of SANGUINATE® (PEGylated carboxyhemoglobin bovine) on cardiopulmonary bypass functionality using a bovine whole blood model of normovolemic hemodilution.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass carries a high risk of bleeding and need for blood transfusion. Blood administration is associated with increased rates of morbidity and mortality. Perioperatively, strategies are often employed to reduce blood transfusions in high-risk patients or in situations where blood transfusion is contraindicated. Normovolemic hemodilution is a blood conservation technique used during cardiac surgery that involves replacement of blood with fluids. SANGUINATE® (PEGylated carboxyhemoglobin bovine) is a novel hemoglobin-based oxygen carrier that can deliver oxygen effectively to tissues in the presence of severe hypoxia. The use of a hemoglobin-based oxygen carrier during hemodilution may augment tissue oxygen delivery and reduce blood transfusion. METHODS: Six standardized cardiopulmonary bypass runs simulating normovolemic hemodilution using varying proportions of bovine whole blood and SANGUINATE were performed. Pump speed, flow rate, line pressures, hemoglobin concentration, oxygenation, and degree of anticoagulation were assessed at regular intervals. Membrane oxygenators and arterial line filters were inspected for evidence of clotting following each run. RESULTS: Increases in the pressure drop across the membrane oxygenator were detected during runs 5 and 6. Median activated clotting time values were able to be maintained at goal during the runs, and SANGUINATE did not appear to be thrombogenic. Hemoglobin concentration decreased following the addition of SANGUINATE. Oxygenation was maintained during all runs that included SANGUINATE. CONCLUSION: SANGUINATE does not impact the performance of the cardiopulmonary bypass circuit in a bovine whole blood model. The results support further evaluation of SANGUINATE in the setting of normovolemic hemodilution and cardiopulmonary bypass.

Comparison of three infant venous reservoirs with vacuum-assisted venous drainage during varying levels of cardiotomy suction.

BACKGROUND: Vacuum-assisted venous drainage has gained widespread use within the pediatric perfusion community for use during cardiopulmonary bypass. It is questioned whether its efficiency may be compromised with application of excessive cardiotomy suction to the infant hard-shell venous reservoir. An in vitro simulation circuit was used to research this phenomenon. A comparison of three different infant hard-shell venous reservoirs also took place to determine if one reservoir type was more advantageous when handling cardiotomy suction. The reservoirs tested were the Maquet VHK 11000, Medtronic Affinity Pixie, and Terumo Capiox FX05. METHODS: The in vitro simulation circuit consisted of a 1 L reservoir bag that was cannulated at one access point with an Edwards Lifesciences 10Fr aortic cannula and the other access area with an Edwards Lifesciences 10Fr right angle venous cannula and 12Fr right angle venous cannula that were joined together. Key points of measurement and response variables were the pressures on the connection of the venous cannulas, inlet of the venous reservoir, and flow through the venous line. Vacuum was applied and manipulated with a Maquet VAVD Controller to settings of -20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg, and -60 mmHg. Cardiotomy suction was added at settings of 1 LPM, 2 LPM, 3 LPM, and 4 LPM. Values from each response variable were monitored and recorded. These data were utilized to compare the reservoirs with a random coefficient model for each response variable. CONCLUSIONS: There is an adverse effect of excessive cardiotomy suction on the efficacy of vacuum-assisted venous drainage in infant hard-shell venous reservoirs. There is no significant difference between the VHK 11000, Pixie, and FX05 regarding their ability to handle this occurrence. An important discovery was that the FX05 showed a greater transfer of vacuum to the venous cannulas and reservoir inlet.

In vitro evaluation of Capiox FX05 and RX05 oxygenators in neonatal cardiopulmonary bypass circuits with varying venous reservoir and vacuum-assisted venous drainage levels.

The purpose of this study was to evaluate the hemodynamic properties and microemboli capture associated with different vacuum-assisted venous drainage (VAVD) vacuum levels and venous reservoir levels in a neonatal cardiopulmonary bypass circuit. Trials were conducted in 2 parallel circuits to compare the performance of Capiox Baby RX05 oxygenator with separate AF02 arterial filter to Capiox FX05 oxygenator with integrated arterial filter. Arterial cannula flow rate to the patient was held at 500 mL/min and temperature maintained at 32°C, while VAVD vacuum levels (0 mm Hg, -15 mm Hg, -30 mm Hg, -45 mm Hg, -60 mm Hg) and venous reservoir levels (50 mL, 200 mL) were evaluated in both oxygenators. Hemodynamic parameters measuring flow, pressure, and total hemodynamic energy were made in real time using a custom-made data acquisition system and Labview software. Nearly 10 cc bolus of air was injected into the venous line and gaseous microemboli detected using an Emboli Detection and Classification Quantifier. Diverted blood flow via the arterial filter's purge line and mean pressures increased with increasing VAVD levels (P < 0.01). Mean pressures were lower with lower venous reservoir levels and were greater in RX05 groups compared to FX05 (P < 0.01). Microemboli detected at the preoxygenator site increased with higher VAVD vacuum levels and lower venous reservoir levels (P < 0.01). The amount of microemboli captured by the FX05 oxygenator with integrated arterial filter was greater than by the RX05 oxygenator alone, although both oxygenators were able to clear microemboli before reaching the pseudo-patient.

Computational investigation of hemodynamics in hardshell venous reservoirs: A comparative study.

Extracorporeal circulation using heart-lung-machines is associated with a profound activation of corpuscular and plasmatic components of circulating blood, which can also lead to deleterious events such as systemic inflammatory response and hemolysis. Individual components used to install the extracorporeal circulation have an impact on the level of activation, most predominantly membrane oxygenators and hardshell venous reservoirs as used in extracorporeal systems. The blood flows in two different hardshell reservoirs are computationally investigated. A special emphasis is placed on the prediction of an onset of transition and turbulence generation. Reynolds-averaged numerical simulations (RANS) based on a transitional turbulence model, as well as large eddy simulations (LES) are applied to achieve an accurate prediction. In the LES analysis, the non-Newtonian behavior of the blood is considered via the Carreau model. Blood damage potential is quantified applying the Modified Index of Hemolysis (MIH) based on the predicted flow fields. The results indicate that the flows in both reservoirs remain predominantly laminar. For one of the reservoirs, considerable turbulence generation is observed near the exit site, caused by the specific design for the connection with the drainage tube. This difference causes the MIH of this reservoir to be nearly twice as large as compared to the alternative design. However, a substantial improvement of these performance criteria can be expected by a local geometry modification.