Perfusion

Veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with refractory cardiopulmonary failure. This study evaluates the short-term (to discharge) and longer-term (1 year) survival among older (⩾65 years) versus younger (<65 years) adults, adjusted for comorbidities, in a diverse cohort of V-A ECMO patients.

This was a retrospective cohort analysis of 131 adult patients (28% ⩾65 years old) who received V-A ECMO at an academic medical center from 2004-2013. Demographics, comorbidities and surgical characteristics were abstracted from the medical records and verified. Mortality status at discharge and at one year post-ECMO were determined by the hospital clinical information system, updated monthly with Social Security Death Index data. Cox proportional hazard analyses were conducted to evaluate associations between age strata and mortality at discharge and at one year post ECMO initiation, adjusted for covariates.

The survival rate following V-A ECMO was 48% (n=68/131) to discharge and 44% (n=58/131) to one year. Age ⩾65 versus <65 was significantly associated with increased mortality during hospitalization (HR:2.03; 95%CI=1.23-3.33) and at one year (HR:1.81; 95% CI=1.12-2.93); these associations were attenuated and did not retain statistical significance after adjustment for comorbidities (HR:1.61; 95%CI=0.90-2.88 and HR:1.42; 95% CI=0.81-2.50, respectively). Statistically significant predictors of mortality at discharge and one year included history of coronary artery bypass graft, peripheral vascular disease and renal failure/dialysis (p<0.05).

Older age was not independently associated with short-term or longer-term survival among V-A ECMO patients, but may reflect greater comorbidity, suggesting that age alone may not disqualify patients from V-A ECMO therapy.

Experimental circuits for biomaterial surface testing are frequently limited by the tested blood volume, composition of the circuit, flow conditions and the use of animal blood. This report describes an ex vivo set-up for simulated cardiopulmonary bypass with human blood perfusion. We investigated the clinical generalizability of the observed effects on hematological and metabolic parameters and the hemocompatibility of the system.

The simulated cardiopulmonary bypass circuit consisted of a heparin-coated tubing system connected to an oxygenator and a venous reservoir. Normothermic flow of blood obtained from healthy donors was maintained at 2.4 L/min/m² by a roller pump. Heparin was dosed to obtain a target activated clotting time (ACT) ⩾500 s. Blood was drawn at baseline and 0, 10, 60 and 120 minutes following the initiation of blood flow to determine hematological and metabolic parameters and the hemocompatibility of the extracorporeal system. Data were analyzed using repeated measures ANOVA.

Two hours of blood perfusion resulted in a small, but clinically unimportant reduction in hematocrit, whereas hemoglobin levels and red blood cell, platelet and leukocyte counts remained stable. There was a significant increase in ACT throughout the experiment. While pO₂ levels and the pH remained unaltered during the experiment, pCO₂ values decreased from 51 ± 6 mmHg at T0 to 41 ± 3 mmHg at T120 (p<0.001). Simulated cardiopulmonary bypass induced a two-fold increase in C3a (p=0.001) while tissue factor was decreased from 44 ± 14 pg/mL at T0 to 38 ± 13 pg/mL at T120 (p=0.009). Levels of CD40L, prothrombin fragment 1+2, β-thromboglobulin and factor VIIa remained stable over time.

The ex vivo set-up for simulated cardiopulmonary bypass mimicked the clinical cardiosurgical setting. Exposure of fresh donor blood to the extracorporeal circuit showed a good hemocompatibility, indicated by maintained hematological parameters and a mild immune response.

Does additional postoperative collection and processing of mediastinal shed blood with a cell salvage device reduce the number of allogeneic blood transfusions compared to intraoperative cell salvage alone?

A single-centre cohort study in which adult patients with coronary artery bypass grafting or aortic valve replacement were allocated to either a C.A.T.S^® group with intraoperative blood processing only or a CardioPat^® group with both intra- and postoperative blood processing. The primary endpoint was the number of allogeneic blood transfusions during hospital admission.

The study included 99 patients; 50 in the C.A.T.S^® and 49 in the CardioPat^® group.

There was no difference in the number of red blood cells (RBC) (C.A.T.S^® group 43 units versus CardioPat^® 50 units, p=0.74), fresh frozen plasma (C.A.T.S^® 8 units versus CardioPat^® 8 units, p=1.00) or platelets (C.A.T.S^® 5 units versus CardioPat^® 4 units, p=1.00) transfused during the hospital stay.

Cardiac creatinine kinase (CK-MB) and troponin levels did not differ between the groups although a significant time effect (p<0.001) was present. Creatinine kinase (CK) levels were not different between the groups three hours after arrival in the intensive care unit (ICU) (CardioPat^® group versus C.A.T.S^® group, p=0.17). But, compared to the C.A.T.S^® group on the first (350 [232-469] IU/L) and second postoperative days (325 [201-480] IU/L), the increase in CK levels was more in the CardioPat^® group on the first (431 [286-642] IU/L, p=0.02) and second postoperative days (406 [239-760] IU/L, p=0.05), resulting in a difference between the groups (p=0.04)

Postoperative cell salvage does not reduce transfusion requirements compared to intraoperative cell salvage alone, but results in elevated total CK levels that suggest haemolysis.

We measured and compared changes in the percentage of cells expressing CD80, CD86, CD40, HLA-DR and the expression of these molecules on B cells and monocytes of patients who underwent either on-pump, mini on-pump or off-pump cardiac surgery.

Blood samples from patients who underwent either on-pump, mini on-pump or off-pump cardiac surgery were collected before surgery, instantly after surgery and on the 1^st, 3^rd and 7^th days after surgery. Surface expression of CD80, CD86, CD40 and HLA-DR molecules was determined by flow cytometry.

Our results show that all three surgical techniques altered the expression of these molecules, as well as the percentage relative number of specific cell populations. We identified statistically significant differences when comparing different surgical techniques. On-pump surgery revealed a more pronounced impact on the phenotype of immune system cells than the other techniques. Therefore, it is likely that the function of immune cells is changed the most by on-pump surgery. We found a lower decrease in the number of CD80⁺ monocytes and a lower drop in the CD40 expression on monocytes in off-pump patients in comparison with on-pump patients.

All the types of cardiac surgical techniques, off-pump, on-pump and modified mini-invasive on-pump, are associated with changes in CD80, CD86, CD40 and HLA-DR expression. We found several significant differences in the expression of the selected molecules when we compared all three groups of patients.

To compare the emboli filtration efficiency of five integrated or non-integrated oxygenator-filter combinations in cardiopulmonary bypass circuits.

Fifty-one adult patients underwent surgery using a circuit with an integrated filtration oxygenator or non-integrated oxygenator with a separate 20 µm arterial line filter (Sorin Dideco Avant D903 + Pall AL20 (n=12), Sorin Inspire 6 M + Pall AL20 (n=10), Sorin Inspire 6M F (n=9), Terumo FX25 (n=10), Medtronic Fusion (n=10)). The Emboli Detection and Classification quantifier was used to count emboli upstream and downstream of the primary filter throughout cardiopulmonary bypass. The primary outcome measure was to compare the devices in respect of the median proportion of emboli removed.

One device (Sorin Inspire 6 M + Pall AL20) exhibited a significantly greater median percentage reduction (96.77%, IQR=95.48 – 98.45) in total emboli counts compared to all other devices tested (p=0.0062 – 0.0002). In comparisons between the other units, they all removed a greater percentage of emboli than one device (Medtronic Fusion), but there were no other significant differences.

The new generation Sorin Inspire 6 M, with a stand-alone 20 µm arterial filter, appeared most efficient at removing incoming emboli from the circuit. No firm conclusions can be drawn about the relative efficacy of emboli removal by units categorised by class (integrated vs non-integrated); however, the stand-alone 20 µm arterial filter presently sets a contemporary standard against which other configurations of equipment can be judged.

Previously, we reported that the oxyhemoglobin dissociation curve is shifted leftward in patients who receive autologous umbilical cord blood (UCB) during neonatal open heart surgery. In this study, we assessed whether allowing the pCO₂ to rise during hypothermic cardiopulmonary perfusion would shift the curve back to the right and improve tissue oxygenation.

The study population included prenatally diagnosed patients with transposition of the great arteries. The study cohort was divided into two groups and consisted of early patients originally managed with lower pCO₂ levels (Group I, n=42, 2009-12) and later patients subsequently managed with higher pCO₂ levels (Group II, n=38, 2012-14).

Patients received similar volumes of collected autologous UCB (Group I, 80 ml; Group II, 75ml, p=0.207) with a similar mean level of HbF during CPB (Group I, 90±8%; Group II, 87±9%, p=0.310). Higher levels of pCO₂ during CPB (Group I, 31 mmHg; Group II, 37 mmHg, p=0.011) resulted in a rightward shift of the oxyhemoglobin dissociation curve (increased p₅₀O₂) (Group I, 19.5±3.4 mmHg; Group II, 22.5±2.2 mmHg, p=0.011). The use of a higher pCO₂ strategy was associated with decreased serum lactate during CPB (Group I, 4.7±2 mmol/l; Group II, 2.8±1.4 mmol/l, p=0.001), decreased duration of mechanical ventilation (Group I, 46h; Group II, 22h, p<0.001) and decreased of length of intensive care unit (ICU) stay (Group I, 7.6±2.6, Group II, 5.6±2.2, p=0.003)

A higher pCO₂ during CPB in neonates who underwent open heart surgery using UCB resulted in a rightward shift of the oxyhemoglobin dissociation curve and was associated with improved serum lactate levels.

Dabigatran etexilate is a direct thrombin inhibitor approved for use in patients with non-valvular atrial fibrillation. There is no currently available pharmacological therapy to reverse this renally cleared anticoagulant. Dabigatran has a low level of plasma protein binding and has been considered dialyzable. We used a pig model with renal artery ligation to exclude intrinsic drug excretion to examine the efficacy of ultrafiltration (UF) during cardiopulmonary bypass (CPB) for dabigatran removal.

Dabigatran was intravenously infused (20 mg) in Yorkshire pigs (male, n=7, 70±1 kg) following renal artery ligation. CPB with UF was initiated after heparinization and continued until a total volume of 6 liters of UF effluent was removed. Serial labs, including dabigatran concentration, activated coagulation times (ACT), hematocrit and creatinine were drawn at intervals before the start of CPB and then incrementally during UF (0, 2, 4 and 6 L removed). Hemodialysis (HD) was performed on one animal following UF.

Dabigatran concentration (ng/mL) rose from undetectable levels at baseline to 296±70 (p<0.05) at the conclusion of infusion, but dropped significantly upon administration of heparin (178±40, p<0.05). A further decrement in dabigatran concentration was observed from the administration of heparin to the start of CPB (to 135±28, p<0.05). Once on CPB, dabigatran remained stable, with the end UF (eUF) dabigatran concentration being 133±34. Dabigatran concentration in the UF effluent was measured in one animal and was 98.8, with 6 L of effluent having been removed. The total recovery of dabigatran was calculated to be less than 5%. Dabigatran concentrations also did not decrease appreciably with HD on CPB following UF.

UF in conjunction with CPB was ineffective at removing dabigatran. Heparin demonstrated a dabigatran-lowering effect, suggesting a possible drug interaction or assay impairment. Based on these findings, emergent cardiac surgery with UF on cardiopulmonary bypass to remove dabigatran is not advisable. Alternative forms of drug removal or reversal must be identified.