Retrograde autologous priming in surgery of thoracic aortic aneurysm

Retrograde autologous priming in surgery of thoracic aortic aneurysm Abstract View largeDownload slide View largeDownload slide OBJECTIVES Surgery of thoracic aortic aneurysm (TAA) is associated with blood loss and coagulopathy and a high need for red blood cell (RBC) volume. Retrograde autologous priming (RAP) decreases haemodilution during cardiopulmonary bypass (CPB). The aim of this study was to show the effect of RAP during surgery of TAA repair on haemodilution, the need for RBC transfusion and the postoperative course compared to conventional CPB (cCPB). METHODS A retrospective study was performed on 120 patients with TAA. Half of these patients underwent cCPB and the other half received RAP. Statistical analysis was performed using IBM SPSS statistics 23. The χ2 test, the Fisher’s exact tests, the independent t-test and the Mann–Whitney U-test were used. Statistical significance was assumed at P-value <0.05. RESULTS Lower blood product requirements were observed for the RAP group regarding the transfusion of intraoperative RBC (0.87 ± 1.33 vs 1.97 ± 2.43, P = 0.013), postoperative RBC (0.57 ± 1.4 vs 1.32 ± 1.82, P = 0.002) and postoperative fresh frozen plasma (0.52 ± 1.63 vs 1.48 ± 3.32, P = 0.036). The postoperative drainage loss showed significantly lower measurements for the RAP group after 6 h (295.9 ± 342.6 vs 490.6 ± 414.4 ml, P ≤ 0.001), 12 h (450.1 ± 415.5 vs 652.1 ± 463.9 ml, P < 0.001) and 24 h (693.1 ± 483.9 vs 866.4 ± 508.4 ml, P = 0.004). CONCLUSIONS RAP is a safe and easy method to reduce RBC transfusion in TAA surgery without any adverse effects on the clinical outcome. We were also able to show beneficial effects on fresh frozen plasma requirements and postoperative chest drainage volume. Furthermore, improved microcirculation can be suspected. In consequence, we have implemented RAP as a clinical standard during thoracic aortic surgery. Aortic aneurysm, Retrograde autologous priming, Transfusion, Extracorporeal circulation, Cardiac surgery INTRODUCTION Cardiac surgery is the largest consumer of blood products in medicine. Although believed lifesaving, transfusion carries substantial adverse risks [1]. Surgery of thoracic aortic aneurysm (TAA) is associated with blood loss and coagulopathy and is shown to be one of the procedures with the highest red blood cell (RBC) volume needed [1]. Because cardiopulmonary bypass (CPB) is required for the procedure, additional haemodilution caused by standard crystalloid priming also affects haemoglobin (Hb) levels as well as haemostasis. Both blood loss and haemodilution can result in anaemia, often requiring the administration of RBC transfusion. Furthermore, the effects on haemostasis may cause the need for fresh frozen plasma (FFP) and platelet concentrates. The negative impact of homologous blood transfusion on the short-term outcome, such as postoperative pneumonia, sepsis, longer hospital stay, nosocomial infections and renal failure, has been demonstrated in several studies [1–4]. Other observations regarding the long-term effects of RBC transfusion show evidence for increased postoperative morbidity and mortality [5, 6]. Considering the adverse effects on the postoperative course and complications, the immense cost factor and general shortage of blood products, many studies in the past have aimed to prove the effects of blood conservation strategies during cardiac surgery to reduce the RBC requirements. Among these strategies, retrograde autologous priming (RAP) has been considered a safe and easy method to decrease haemodilution during CPB [7]. When performing RAP, haemodilution is reduced through passive exsanguination of the arterial and venous line prior to CPB [8]. This method was first described by Rosengart et al. in 1998, and from there it was constantly optimized and investigated by various authors documenting the effect of reduced RBC transfusion when using RAP [9–14]. Most trials investigated the positive effects of RAP during coronary bypass grafting, few during congenital cardiac surgery or isolated valve replacement. Therefore, this study aims to show the effect of RAP during open surgery of TAA repair on haemodilution, the need for RBC transfusion and the postoperative course compared to conventional CPB (cCPB). MATERIALS AND METHODS Patient population The study was approved by the local Ethics Committee. A retrospective study was performed on 120 patients with ascending aortic aneurysm at the University Hospital in Bonn. All patients underwent elective cardiac surgery with at least replacement of the ascending aorta in the period from May 2010 until June 2016. All patients required CPB. In 2015, the concept of RAP was applied for the first time routinely in aortic surgery at our clinic. The 60 patients in the RAP group are those operated after the cutover to the RAP technique. This patient collective was compared to a consecutive historical patient collective with the same indication before implementation of RAP, therefore operated with cCPB. These patient selections were then checked for comparability concerning demographic data and comorbidities (Table 1) as well as the surgical procedure (Table 2). Exclusion criteria were emergency surgery, aortic dissections and aortic rupture. Information on preoperative baseline characteristics, risk factors and comorbidities, intraoperative detail and postoperative care was collected for the study. Table 1: Demographic data and comorbidities cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b Values are expressed as means ± standard deviation or patient numbers (%). a χ2 test. b χ2 weighted. c Independent t-test. d t-test weighted. e Mann–Whitney U-test. f Fisher’s exact test. BMI: body mass index; cCPB: conventional cardiopulmonary bypass; CHD: coronary heart disease; COPD: chronic obstructive pulmonary disease; PAD: peripheral artery disease; RAP: retrograde autologous priming. Table 1: Demographic data and comorbidities cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b Values are expressed as means ± standard deviation or patient numbers (%). a χ2 test. b χ2 weighted. c Independent t-test. d t-test weighted. e Mann–Whitney U-test. f Fisher’s exact test. BMI: body mass index; cCPB: conventional cardiopulmonary bypass; CHD: coronary heart disease; COPD: chronic obstructive pulmonary disease; PAD: peripheral artery disease; RAP: retrograde autologous priming. Table 2: Intraoperative data cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b t-test weighted. c χ2 test. d χ2 weighted. *Combination of aortic valve replacement and supracoronary ascending aortic replacement. CABG: coronary artery bypass grafting; cCPB: conventional cardiopulmonary bypass; CPB: cardiopulmonary bypass; NS: not significant; RAP: retrograde autologous priming. Table 2: Intraoperative data cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b t-test weighted. c χ2 test. d χ2 weighted. *Combination of aortic valve replacement and supracoronary ascending aortic replacement. CABG: coronary artery bypass grafting; cCPB: conventional cardiopulmonary bypass; CPB: cardiopulmonary bypass; NS: not significant; RAP: retrograde autologous priming. Management of extracorporeal circulation All surgeries were performed using a Terumo® Advanced Perfusion System 1 (Terumo Cardiovascular Systems, Ann Arbor, MI, USA). The extracorporeal circuit included a venous hard-shell cardiotomy reservoir (Maquet, Wayne, NJ, USA), a roller pump system and a membrane oxygenator (Quadrox® oxygenator Maquet, Wayne, NJ, USA) equipped with a heat exchanger and an arterial filter. The non-heparin coated system was primed with a crystalloid solution (Jonosteril®, Fresenius, Bad Homburg, Germany) and 10 000 U of heparin. Conventional cardiopulmonary bypass Blood from the right atrium was drained through the venous line, passively filling the venous cardiotomy reservoir and the following membrane oxygenator by using the hydrostatic pressure gradient. Here, it was saturated with oxygen and desaturated from carbon dioxide. Passing through the arterial pump, the blood then returned to the patient through the arterial cannula. Additional roller pumps were used for the left ventricular vent and the cardiotomy suction, both joining the venous cardiotomy reservoir. Retrograde autologous priming In the RAP group, the CPB circuit was initially primed with the same volume and consistency of fluid as the cCPB group. The only structural difference from the cCPB system was a recirculation bag as shown in Fig. 1. Before and while performing the RAP procedure, a minimum systolic blood pressure of ∼90 mmHg was maintained, if necessary with short-term administrations of vasopressors (Noradrenalin). This administration was implemented in mutual consultation with the perfusionist and anaesthetist. Before CPB initiation, the fluid from the arterial line was drained into the recirculation bag by displacing priming solution with the patient’s blood from the aorta by using arterial pressure. After the arterial line was clamped, the occlusion clamp on the venous line was released to slowly replace the crystalloid fluid with the patient’s blood using the hydrostatic pressure gradient. If any risks for the patient emerged or high amounts of vasopressors were necessary to perform RAP, further fluid displacements were consensually refrained from. In our study, patients with RAP procedures reaching fluid displacements of more than 200 ml were included. Figure 1: View largeDownload slide Scheme of the retrograde autologous priming technique. Figure 1: View largeDownload slide Scheme of the retrograde autologous priming technique. After the RAP procedure was performed, the recirculation bag remained connected to the venous reservoir, so that crystalloid volume could be administered during CPB upon haemodynamic requirements. The RAP procedure required ∼2–3 min. Surgical strategy Anaesthesia Sufentanil citrate and etomidate were used for anaesthetic induction and sufentanil citrate and either isoflurane or sevoflurane for maintenance. Anticoagulation for CPB was achieved with initially 400 U/kg heparin, and the activated clotting time was kept over 480 s during CPB. After CPB, the heparin was 100% antagonized with protamine. One gram of tranexamic acid was administered at the end of the operation according to the standard protocol at our clinic. Surgical management All operations were performed by experienced surgeons. Access was achieved via complete median sternotomy, followed by full heparinization, selection of the arterial cannulation site (either the proximal aortic arch or the distal ascending aorta) and cannulation of the right atrium with a 2-stage venous cannula. After transition to extracorporeal circulation, a mean minimal rectal temperature of 32.89°C (cCPB) and 32.55°C (RAP) was achieved. Following standard protocol at our institution, myocardial protection was accomplished with 2000 ml antegrade cold cardioplegic solution (Custodiol® HTK Bretschneider, Dr. Franz Kohler Chemie GmbH, Bensheim, Germany), which was administered over 6 min. The surgical procedures did not differ significantly between the 2 groups. A haemofilter was connected after the arterial pump as bypass. The filtration rate was dependent on the current flow rate, which was approximately 400–500 ml/min. Haemofiltration was contained during surgery in both groups. Postoperative care All patients were transferred to the cardio-surgical intensive care unit (ICU) after surgery. Sedation was performed with propofol and sufentanil citrate. Early extubation and transfer to the intermediate care unit were attempted in all cases. Transfusion criteria conformed to the ‘Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives’ (4th revised edition) by the German Medical Association [15]. As per the guidelines, the indication for RBC transfusion was Hb <8 g/dl, as all cardiac surgery patients have limited compensation capabilities. Criteria for transfusion were the same in both patient groups. According to the Guidelines, in acquired platelet aggregation disorders leading to microvascular bleeding (e.g. after cardiopulmonary bypass), transfusion triggers cannot be based on platelet counts, but rather on the clinical disposition to bleeding and is recommended until haemostasis is achieved [15]. Therefore, the decision for a platelet or plasma transfusion was in all cases a clinical one made by the responsible surgeon. Statistical analysis Statistical analysis was performed using IBM SPSS statistics 23. Categorical data are presented as numbers and percentages. Differences were explored with the χ2 test or the Fisher’s exact tests when the number of expected frequencies in a cell was <5. Continuous data were reported as mean ± standard deviation or median and interquartile range. When normal distribution was assumed, the independent t-test was applied and the Mann–Whitney U-test when normal distribution was not assumed. Statistical significance was considered at P-value <0.05. To reduce potential selection bias due to possible structural differences within the retrospective collective, we additionally performed inverse probability weighting using propensity score. For the score model, we used the following variables: age, sex, body mass index (BMI), EUROSCORE II and hypertension. RESULTS The profile of the patient population is shown in Table 1, which summarizes the demographic data and comorbidities. The 2 groups were comparable in height, weight, age, gender and BMI. There was also an equivalent incidence for comorbidities and similar heart surgery-specific risk factors. Intraoperative data are presented in Table 2. The study groups were compared in terms of the surgical procedure for aortic replacement and the number of concurrent coronary bypass operations. Average aortic cross-clamp time, reperfusion time and total CPB time, as well as the achieved mean minimal rectal temperature, were also similar in both groups. Regarding the amount of priming volume, a significant difference was observed (P < 0.001). In the RAP group, the priming fluid was reduced to a mean volume of 661.7 ± 204.9 ml compared to 1610.7 ± 310.2 ml in the cCPB group. The CPB balance at the end of the surgery was −133.2 ± 1401 ml for the cCPB group and 76.60 ± 1014 ml for the RAP group, which means that even though on average more volume was filtered out the blood consumption was higher in the cCPB group. To assess the influence of priming volume on haemodilution, Hb values were used as an indicator. The Hb level development is shown in Fig. 2A. Intraoperative measurements were taken before CPB initiation and every 30 min during CPB. The subsequent Hb measurements were taken directly after the patient’s transfer to ICU, as well as 6, 12, 24 and 48 h postoperative. Mean preoperative Hb values were 12.99 ± 1.43 mg/dl in the RAP group and 12.66 ± 1.5 mg/dl in the cCPB group (P = 0.218). Thirty minutes after CPB initiation, a notable greater decline of Hb levels was monitored in the cCPB group (8.95 ± 1.7 mg/dl vs 10.55 ± 1.61 mg/dl, P < 0.001). This decline resulted in higher requirements for intraoperative RBC transfusion for the cCPB group, as 53.3% of these patients received RBC transfusion in contrast to 36.7% of the patients in the RAP group. RBC numbers and other blood products are summarized in Table 3. Mean intraoperative RBC numbers of 1.97 ± 2.43 in the cCPB and 0.87 ± 1.33 in the RAP group (P = 0.013), as well as postoperative numbers of 1.32 ± 1.82 in the cCPB group vs 0.57 ± 1.4 in the RAP group (P = 0.002), were transfused. In summary, 70% of cCPB patients received RBC transfusion vs 48% in the RAP group. As for the other blood products, the need for platelet concentrates was comparable between the 2 groups. FFP requirements were shown to be significantly lower (P = 0.036) in the RAP group regarding the need for transfusion on ICU. The intraoperatively transfused FFP numbers, however, were similar in both groups (P = 0.437). Table 3: Transfusion of blood components cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a a Mann–Whitney U-test. b χ2 test. c CPB: conventional cardiopulmonary bypass; FFP: fresh frozen plasma; ICU: intensive care unit; IQR: interquartile range; PC: platelet concentrates; RAP: retrograde autologous priming; RBC: red blood cell; SD: standard deviation. Table 3: Transfusion of blood components cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a a Mann–Whitney U-test. b χ2 test. c CPB: conventional cardiopulmonary bypass; FFP: fresh frozen plasma; ICU: intensive care unit; IQR: interquartile range; PC: platelet concentrates; RAP: retrograde autologous priming; RBC: red blood cell; SD: standard deviation. Figure 2: View largeDownload slide Laboratory values at various points in time comparing the cCPB group and the RAP group. (A) Haemoglobin levels (g/dl); (B) lactate levels (mmol/l); (C) creatinine kinase levels (U/l); (D) troponin levels (ng/ml). CPB: cardiopulmonary bypass; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; Pre-Op: preoperative; Post-Op: postoperative; RAP: retrograde autologous priming. Figure 2: View largeDownload slide Laboratory values at various points in time comparing the cCPB group and the RAP group. (A) Haemoglobin levels (g/dl); (B) lactate levels (mmol/l); (C) creatinine kinase levels (U/l); (D) troponin levels (ng/ml). CPB: cardiopulmonary bypass; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; Pre-Op: preoperative; Post-Op: postoperative; RAP: retrograde autologous priming. The pH and lactate values were concurrently measured with the Hb levels by blood gas analysis before CPB initiation, during CPB and until 24 h postoperative. In addition, the maximum lactate on ICU, as well as the lowest pH on ICU, was determined. The lactate development is demonstrated in Fig. 2B, illustrating a higher increase in postoperative lactate levels in the cCPB group compared to the RAP group, with a mean maximum lactate of 3.33 ± 2.25 mmol/l in the cCPB group vs 2.71 ± 1.25 mmol/l in the RAP group (P = 0.053). Consistent with the difference in lactate increase, the mean minimum pH level on ICU showed lower values in the cCPB group (P = 0.018). Troponin and creatine kinase levels were measured preoperatively and postoperatively, as well as on first, second and third postoperative days. The course of creatine kinase values is demonstrated in Fig. 2C. Coming from initially lower baseline values on the cCPB side, the course shows a change to slightly higher postoperative measurements for the cCPB group compared to the RAP group. The development of troponin values is illustrated in Fig. 2D. The troponin levels show a mild tendency to increased values in the cCPB group. Parameters for kidney function, urea and creatinine levels were monitored preoperatively and postoperatively and on first, second and third postoperative days. Both urea and creatinine values were comparable between the groups. Concurrent measurements were made for bilirubin, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase, which showed no notable difference either. The course of leucocyte levels was also independent of the perfusion method. Preoperative platelet levels showed a non-significant difference between the 2 groups. In the postoperative development, however, a tendency to decreased platelet levels after transfer to ICU (126.7 × 10³/µl cCPB vs 140.3 × 10³/µl RAP, P = 0.018), as well as on the first postoperative day (144.0 × 10³/µl cCPB vs 159.1 × 10³/µl RAP, P = 0.027), was observed. The possible impact of postoperative haemodilution on the Hb levels and consequential transfusion was considered by calculating the total fluid balance on ICU after 6, 12 and 24 h. The fluid balance was comparable at all points of the calculation. At the end point of calculation after 24 h, the total fluid balance amounted to +3469 ± 2064 ml in the cCPB group and +3244 ± 1652 ml in the RAP group (P = 0.717). Furthermore, drainage loss was also measured after 6, 12 and 24 h and is demonstrated in Fig. 3. A statistically significant difference in drainage loss after 6 h (490.6 ± 414.4 ml for cCPB vs 295.9 ± 342.6 ml for RAP, P ≤ 0.001), as well as after 12 h (652.1 ± 463.9 ml for cCPB vs 450.1 ± 415.5 ml for RAP, P < 0.001) and after 24 h (866.4 ± 508.4 ml for cCPB vs 693.1 ± 483.9 ml for RAP, P = 0.004), was observed. Figure 3: View largeDownload slide Postoperative drainage loss over the course of time (ml). cCPB: conventional cardiopulmonary bypass; Post-Op: postoperative; RAP: retrograde autologous priming. Figure 3: View largeDownload slide Postoperative drainage loss over the course of time (ml). cCPB: conventional cardiopulmonary bypass; Post-Op: postoperative; RAP: retrograde autologous priming. The postoperative development was measured by length of the ICU stay, ventilation time und overall hospital stay and revealed no statistically relevant differences. Complications on ICU such as occurrence of bleeding, infections, pleural effusion, kidney failure and cardiac arrhythmias were unaffected by the perfusion strategy. A mild tendency towards reduced neurological outcome was shown, as 14 cases of delirium and 1 incidence of stroke occurred in the cCPB group compared to slightly lower numbers of 10 cases of delirium and no stroke incidence in the RAP group. Cases of death did not occur at all. The clinical outcome is shown in Table 4 in detail. Table 4: Clinical outcome cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b χ2 test. c Fisher’s exact test. ARF: acute renal failure; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; RAP: retrograde autologous priming. Table 4: Clinical outcome cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b χ2 test. c Fisher’s exact test. ARF: acute renal failure; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; RAP: retrograde autologous priming. DISCUSSION Extracorporeal circulation is still commonly used in cardiac surgery and requires crystalloid priming, which is known to cause haemodilution. In consequence, it results in lower intraoperative Hb levels, which may negatively influence the tissue oxygen delivery, as well as reduction of plasma colloid osmotic pressure and decreased concentration of coagulation factors and platelets. It is documented that severe haemodilution on cCPB is associated with dilutional coagulopathy, bleeding and thrombosis-associated worse outcomes [16]. Furthermore, studies have found a direct association between the nadir haematocrit during CPB and the most major complications during cardiac surgery [17]. The purpose of this study was to explore the effects of RAP during elective TAA surgery on reducing RBC transfusion requirements and other beneficial effects of decreased haemodilution during CPB. By reducing the priming volume to 662 vs 1611 ml (P < 0.001) through RAP, the Hb drop during CPB was significantly decreased (P < 0.001). This fact resulted in a lower need for RBC transfusion in the RAP group. Patients receiving surgery under cCPB had an overall need for transfusion in 70% of the cases. In comparison, only 48.3% of the patients undergoing the RAP procedure received RBC transfusion at all during the entire hospital stay. Furthermore, increased lactate levels (P = 0.053) with concurrent lower pH levels on ICU were monitored in the cCPB group. Both issues can be induced through hypoxia, and the findings allow the conclusion that higher haemodilution during cCPB results in poorer oxygen delivery. Ranucci et al. confirmed the role of early hyperlactataemia as a predictive marker of bad outcomes in cardiac surgery and also indicated haemodilution on CPB as an independent determinant of moderate and severe early postoperative hyperlactataemia [18]. Other studies concurred with these findings and therefore concluded that reduction of haemodilution improves microcirculation perfusion [10]. Other results in this study highlight that CPB-induced haemodilution does affect not only anaemia-related RBC transfusion but also coagulation, postoperative bleeding and FFP requirements. Ranucci et al. [16] recently published an extensive in vivo study, demonstrating the tendency towards coagulopathy in patients with severe haemodilution after cardiopulmonary bypass and showing a decrease in fibrinogen levels in their patients after transfer to ICU, which was proven to be haemodilution related. Our patient population that received a greater volume of crystalloid solution through cCPB showed a greater need for FFP transfusion on ICU, despite intraoperative haemofiltration. Within this implemented retrospective study, coagulopathy-related laboratory values were not recorded routinely for all patients. We can assume that intraoperative haemodilution plays a part in the development of microvascular bleeding after cardiopulmonary bypass. Nevertheless, one can speculate that a primary lower haemodilution due to RAP may have an overall positive impact on the coagulation. Furthermore, there was a significantly higher drainage loss on ICU for the cCPB patients. A possible reason for the elevated drainage loss within the first hours could be coagulopathy-related microvascular bleeding which is suspended after transfusion-induced optimization. Although relevant measurements were not recorded, based on the aforementioned data, one can speculate that the increase of FFP requirements and drainage loss in the cCPB group is caused by haemodilution-related coagulopathy. The greater loss of drainage fluid could also explain the differences in RBC requirements regarding the postoperative period exclusively. In the cCPB group, 47% of the patients had the need for RBC transfusion on ICU vs only 20% in the RAP group. As both within our study as well as in the mentioned studies haemodilution is identified as a cause for an increased need for transfusion during cardiac surgery—against the background of a general shortage of blood products—efforts should be made to reduce this effect. In addition to the use of smaller, patient-adjusted, CPB sets with a per se lower priming volume, RAP can have an additional beneficial effect on transfusion requirements. Furthermore, this beneficial effect can be strengthened by the usage of blood cardioplegia or a higher intraoperative filtration rate. Other studies have outlined the need for transfusion as an independent risk factor for acute kidney injury after surgery on the thoracic aorta [19]. Despite these findings, the creatinine development and incidence of acute kidney injury in our study was independent of the perfusion strategy and transfusion rates. Creatine kinase and troponin levels were also not appreciably affected by the perfusion strategy, although a trend to slightly reduced cardiac markers was observed in the RAP group. Even though the postoperative platelet development showed a statistically significant difference between the groups, the minimal clinical difference is not presumed to have any beneficial impact for the RAP patients. The RAP procedure had no adverse influence on aortic cross-clamp time, reperfusion time and total CPB time, as no prolonged CPB duration was observed. Many studies have evaluated the various negative effects of RBC transfusion on the patient’s long-term and short-term outcome such as pneumonia, nosocomial infections, acute renal failure, prolonged hospital stay and increased postoperative morbidity and mortality [1–6]. Despite the differences in RBC transfusion between our study groups, there were no consequential differences in postoperative complications or outcome. Other studies investigating RAP come to similar results. A meta-analysis on the effects of RAP by Sun et al. including ten randomized controlled trials summarized that RAP could reduce transfusion in adults significantly but had no effect on clinical outcomes [12]. Although there were no statistically relevant differences in the neurological outcome, a certain trend to reduced delirium was observed. Limitations Our study has several limitations. Firstly, this study is a retrospective single-centre study. Secondly, due to the nature of this study, selection bias cannot be excluded. Thirdly, the results show significant differences between RAP and cCPB. However, the reasons for some of these differences can only be speculatively explained based on existing literature. Proper validation is only possible within a larger scale, prospective, randomized study. CONCLUSIONS In summary, we were able to show that RAP is a safe method to reduce RBC transfusion in TAA surgery without any adverse effects on the clinical outcome. Furthermore, it could be shown that the usage of RAP has a positive effect on the need for FFP and the postoperative drainage loss. Due to lower lactate values when using RAP compared to cCPB, an improved microcirculation caused by less haemodilution can be suspected. Against the background of a general shortage of blood products, complications caused by transfusions and consequently higher costs, all possibilities to reduce the need for transfusion should be exploited. As a consequence of our results, we have implemented RAP as an important component of our patient blood management concept also as clinical standard in aortic surgery. Conflict of interest: none declared. REFERENCES 1 Horvath KA , Acker MA , Chang H , Bagiella E , Smith PK , Iribarne A et al. Blood transfusion and infection after cardiac surgery . Ann Thorac Surg 2013 ; 95 : 2194 – 201 . Google Scholar Crossref Search ADS PubMed 2 Likosky DS , Paone G , Zhang M , Rogers MAM , Harrington SD , Theurer PF et al. Red blood cell transfusions impact pneumonia rates after coronary artery bypass grafting . Ann Thorac Surg 2015 ; 100 : 794 – 800 ; discussion 801. Google Scholar Crossref Search ADS PubMed 3 Galas FRBG , Almeida JP , Fukushima JT , Osawa EA , Nakamura RE , Silva CMPDC et al. Blood transfusion in cardiac surgery is a risk factor for increased hospital length of stay in adult patients . J Cardiothorac Surg 2013 ; 8 : 54 . Google Scholar Crossref Search ADS PubMed 4 Taylor RW , O’Brien J , Trottier SJ , Manganaro L , Cytron M , Lesko MF et al. Red blood cell transfusions and nosocomial infections in critically ill patients . Crit Care Med 2006 ; 34 : 2302 – 8 ; quiz 2309. Google Scholar Crossref Search ADS PubMed 5 Koch CG , Li L , Duncan AI , Mihaljevic T , Loop FD , Starr NJ et al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival . Ann Thorac Surg 2006 ; 81 : 1650 – 7 . Google Scholar Crossref Search ADS PubMed 6 Engoren MC , Habib RH , Zacharias A , Schwann TA , Riordan CJ , Durham SJ. Effect of blood transfusion on long-term survival after cardiac operation . Ann Thorac Surg 2002 ; 74 : 1180 – 6 . Google Scholar Crossref Search ADS PubMed 7 Rosengart TK , DeBois W , O’Hara M , Helm R , Gomez M , Lang SJ et al. Retrograde autologous priming for cardiopulmonary bypass: a safe and effective means of decreasing hemodilution and transfusion requirements . J Thorac Cardiovasc Surg 1998 ; 115 : 426 – 39 . Google Scholar Crossref Search ADS PubMed 8 Trapp C , Schiller W , Mellert F , Halbe M , Lorenzen H , Welz A et al. Retrograde autologous priming as a safe and easy method to reduce hemodilution and transfusion requirements during cardiac surgery . Thorac Cardiovasc Surg 2015 ; 63 : 628 – 34 . Google Scholar Crossref Search ADS PubMed 9 Balachandran S , Cross MH , Karthikeyan S , Mulpur A , Hansbro SD , Hobson P. Retrograde autologous priming of the cardiopulmonary bypass circuit reduces blood transfusion after coronary artery surgery . Ann Thorac Surg 2002 ; 73 : 1912 – 8 . Google Scholar Crossref Search ADS PubMed 10 Cheng M , Li J-Q , Wu T-C , Tian W-C. Short-term effects and safety analysis of retrograde autologous blood priming for cardiopulmonary bypass in patients with cardiac valve replacement surgery . Cell Biochem Biophys 2015 ; 73 : 441 – 6 . Google Scholar Crossref Search ADS PubMed 11 Severdija EE , Heijmans JH , Theunissen M , Maessen JG , Roekaerts PH , Weerwind PW. Retrograde autologous priming reduces transfusion requirements in coronary artery bypass surgery . Perfusion 2011 ; 26 : 315 – 21 . Google Scholar Crossref Search ADS PubMed 12 Sun P , Ji B , Sun Y , Zhu X , Liu J , Long C et al. Effects of retrograde autologous priming on blood transfusion and clinical outcomes in adults: a meta-analysis . Perfusion 2013 ; 28 : 238 – 43 . Google Scholar Crossref Search ADS PubMed 13 Teman N , Delavari N , Romano M , Prager R , Yang B , Haft J. Effects of autologous priming on blood conservation after cardiac surgery . Perfusion 2014 ; 29 : 333 – 9 . Google Scholar Crossref Search ADS PubMed 14 Vandewiele K , Bove T , De Somer FMJJ , Dujardin D , Vanackere M , De Smet D et al. The effect of retrograde autologous priming volume on haemodilution and transfusion requirements during cardiac surgery . Interact CardioVasc Thorac Surg 2013 ; 16 : 778 – 83 . Google Scholar Crossref Search ADS PubMed 15 Bundesärztekammer . Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivates . 4th edn . Freiburg im Breisgau : Karger S , 2009 . 16 Ranucci M , Baryshnikova E , Ciotti E , Ranucci M , Silvetti S. Hemodilution on cardiopulmonary bypass: thromboelastography patterns and coagulation-related outcomes . J Cardiothorac Vasc Anesth 2017 ; 31 : 1588 – 94 . Google Scholar Crossref Search ADS PubMed 17 Habib RH , Zacharias A , Schwann TA , Riordan CJ , Durham SJ , Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg 2003 ; 125 : 1438 – 50 . Google Scholar Crossref Search ADS PubMed 18 Ranucci M , Carboni G , Cotza M , Bianchi P , Di Dedda U , Aloisio T. Hemodilution on cardiopulmonary bypass as a determinant of early postoperative hyperlactatemia . PloS One 2015 ; 10 : e0126939. Google Scholar Crossref Search ADS PubMed 19 Kim WH , Park MH , Kim H-J , Lim H-Y , Shim HS , Sohn J-T et al. Potentially modifiable risk factors for acute kidney injury after surgery on the thoracic aorta: a propensity score matched case-control study . Medicine (Baltimore) 2015 ; 94 : e273. Google Scholar Crossref Search ADS PubMed © The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Interactive CardioVascular and Thoracic Surgery Oxford University Press

Retrograde autologous priming in surgery of thoracic aortic aneurysm

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Oxford University Press
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© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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1569-9293
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1569-9285
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10.1093/icvts/ivz014
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Abstract

Abstract View largeDownload slide View largeDownload slide OBJECTIVES Surgery of thoracic aortic aneurysm (TAA) is associated with blood loss and coagulopathy and a high need for red blood cell (RBC) volume. Retrograde autologous priming (RAP) decreases haemodilution during cardiopulmonary bypass (CPB). The aim of this study was to show the effect of RAP during surgery of TAA repair on haemodilution, the need for RBC transfusion and the postoperative course compared to conventional CPB (cCPB). METHODS A retrospective study was performed on 120 patients with TAA. Half of these patients underwent cCPB and the other half received RAP. Statistical analysis was performed using IBM SPSS statistics 23. The χ2 test, the Fisher’s exact tests, the independent t-test and the Mann–Whitney U-test were used. Statistical significance was assumed at P-value <0.05. RESULTS Lower blood product requirements were observed for the RAP group regarding the transfusion of intraoperative RBC (0.87 ± 1.33 vs 1.97 ± 2.43, P = 0.013), postoperative RBC (0.57 ± 1.4 vs 1.32 ± 1.82, P = 0.002) and postoperative fresh frozen plasma (0.52 ± 1.63 vs 1.48 ± 3.32, P = 0.036). The postoperative drainage loss showed significantly lower measurements for the RAP group after 6 h (295.9 ± 342.6 vs 490.6 ± 414.4 ml, P ≤ 0.001), 12 h (450.1 ± 415.5 vs 652.1 ± 463.9 ml, P < 0.001) and 24 h (693.1 ± 483.9 vs 866.4 ± 508.4 ml, P = 0.004). CONCLUSIONS RAP is a safe and easy method to reduce RBC transfusion in TAA surgery without any adverse effects on the clinical outcome. We were also able to show beneficial effects on fresh frozen plasma requirements and postoperative chest drainage volume. Furthermore, improved microcirculation can be suspected. In consequence, we have implemented RAP as a clinical standard during thoracic aortic surgery. Aortic aneurysm, Retrograde autologous priming, Transfusion, Extracorporeal circulation, Cardiac surgery INTRODUCTION Cardiac surgery is the largest consumer of blood products in medicine. Although believed lifesaving, transfusion carries substantial adverse risks [1]. Surgery of thoracic aortic aneurysm (TAA) is associated with blood loss and coagulopathy and is shown to be one of the procedures with the highest red blood cell (RBC) volume needed [1]. Because cardiopulmonary bypass (CPB) is required for the procedure, additional haemodilution caused by standard crystalloid priming also affects haemoglobin (Hb) levels as well as haemostasis. Both blood loss and haemodilution can result in anaemia, often requiring the administration of RBC transfusion. Furthermore, the effects on haemostasis may cause the need for fresh frozen plasma (FFP) and platelet concentrates. The negative impact of homologous blood transfusion on the short-term outcome, such as postoperative pneumonia, sepsis, longer hospital stay, nosocomial infections and renal failure, has been demonstrated in several studies [1–4]. Other observations regarding the long-term effects of RBC transfusion show evidence for increased postoperative morbidity and mortality [5, 6]. Considering the adverse effects on the postoperative course and complications, the immense cost factor and general shortage of blood products, many studies in the past have aimed to prove the effects of blood conservation strategies during cardiac surgery to reduce the RBC requirements. Among these strategies, retrograde autologous priming (RAP) has been considered a safe and easy method to decrease haemodilution during CPB [7]. When performing RAP, haemodilution is reduced through passive exsanguination of the arterial and venous line prior to CPB [8]. This method was first described by Rosengart et al. in 1998, and from there it was constantly optimized and investigated by various authors documenting the effect of reduced RBC transfusion when using RAP [9–14]. Most trials investigated the positive effects of RAP during coronary bypass grafting, few during congenital cardiac surgery or isolated valve replacement. Therefore, this study aims to show the effect of RAP during open surgery of TAA repair on haemodilution, the need for RBC transfusion and the postoperative course compared to conventional CPB (cCPB). MATERIALS AND METHODS Patient population The study was approved by the local Ethics Committee. A retrospective study was performed on 120 patients with ascending aortic aneurysm at the University Hospital in Bonn. All patients underwent elective cardiac surgery with at least replacement of the ascending aorta in the period from May 2010 until June 2016. All patients required CPB. In 2015, the concept of RAP was applied for the first time routinely in aortic surgery at our clinic. The 60 patients in the RAP group are those operated after the cutover to the RAP technique. This patient collective was compared to a consecutive historical patient collective with the same indication before implementation of RAP, therefore operated with cCPB. These patient selections were then checked for comparability concerning demographic data and comorbidities (Table 1) as well as the surgical procedure (Table 2). Exclusion criteria were emergency surgery, aortic dissections and aortic rupture. Information on preoperative baseline characteristics, risk factors and comorbidities, intraoperative detail and postoperative care was collected for the study. Table 1: Demographic data and comorbidities cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b Values are expressed as means ± standard deviation or patient numbers (%). a χ2 test. b χ2 weighted. c Independent t-test. d t-test weighted. e Mann–Whitney U-test. f Fisher’s exact test. BMI: body mass index; cCPB: conventional cardiopulmonary bypass; CHD: coronary heart disease; COPD: chronic obstructive pulmonary disease; PAD: peripheral artery disease; RAP: retrograde autologous priming. Table 1: Demographic data and comorbidities cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Gender (male/female) 38/22 36/24 0.707a 0.856b Age (years) 66.35 ± 11.67 64.92 ± 12.55 0.518c 0.747d Height (cm) 173.3 ± 9.75 172.4 ± 9.92 0.585c 0.535d Weight (kg) 81.02 ± 18.32 83.52 ± 16.45 0.433c 0.774d BMI 26.85 ± 4.52 27.83 ± 4.86 0.254c 0.926d EUROSCORE II 8.02 ± 2.42 7.55 ± 3.17 0.455e 0.697d Hypertension 54 (90) 52 (86.7) 0.570a 0.985b Hypercholesterolaemia 28 (46.7) 35 (58.3) 0.201a 0.136b Type 2 diabetes 9 (15) 6 (12.5) 0.408a 0.325b Smoking history 29 (48.3) 20 (33.3) 0.095a 0.142b CHD 21 (44.7) 26 (43.3) 0.350a 0.094b Myocardial infarction 2 (3.3) 2 (3.3) 1.000f 0.925b Atrial fibrillation 12 (20) 10 (16.7) 0.637a 0.346b COPD 8 (13.3) 11 (18.3) 0.453a 0.419b PAD 1 (1.7) 4 (6.7) 0.364f 0.485b Renal disease 5 (8.3) 2 (3.3) 0.439f 0.493b Stroke 4 (6.7) 3 (5) 1.000f 0.865b Hepatitis 1 (1.7) 2 (3.3) 1.000f 0.388b Malignoma 1 (1.7) 1 (1.7) 1.000f 0.764b Reoperation 3 (5) 3 (5) 1.000f 0.155b Values are expressed as means ± standard deviation or patient numbers (%). a χ2 test. b χ2 weighted. c Independent t-test. d t-test weighted. e Mann–Whitney U-test. f Fisher’s exact test. BMI: body mass index; cCPB: conventional cardiopulmonary bypass; CHD: coronary heart disease; COPD: chronic obstructive pulmonary disease; PAD: peripheral artery disease; RAP: retrograde autologous priming. Table 2: Intraoperative data cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b t-test weighted. c χ2 test. d χ2 weighted. *Combination of aortic valve replacement and supracoronary ascending aortic replacement. CABG: coronary artery bypass grafting; cCPB: conventional cardiopulmonary bypass; CPB: cardiopulmonary bypass; NS: not significant; RAP: retrograde autologous priming. Table 2: Intraoperative data cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) cCPB (n = 60) RAP (n = 60) P-value Weighted analysis Aortic cross-clamp time (min) 118.1 ± 38.63 106.7 ± 36.18 0.107a 0.075b Reperfusion time (min) 29.52 ± 15.09 30.27 ± 15.67 0.885a 0.370b CPB time (min) 157.6 ± 46.85 145.3 ± 47.33 0.142a 0.377b Min. temperature (°C) 32.89 ± 1.87 32.55 ± 1.74 0.082a 0.196b Priming volume (ml) 1610.7 ± 310.2 661.7 ± 204.9 <0.001a <0.001b Additional CABG 8 (13.3) 12 (20) 0.327c 0.138d Surgical procedure NS 0.791d Supracoronary aortic replacement 29 (48.3) 26 (43.3) Wheat procedure* 28 (46.7) 30 (50) Bentall procedure 1 (1.7) 1 (1.7) Biological Bentall procedure 0 (0) 1 (1.7) David procedure 2 (3.3) 2 (3.3) Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b t-test weighted. c χ2 test. d χ2 weighted. *Combination of aortic valve replacement and supracoronary ascending aortic replacement. CABG: coronary artery bypass grafting; cCPB: conventional cardiopulmonary bypass; CPB: cardiopulmonary bypass; NS: not significant; RAP: retrograde autologous priming. Management of extracorporeal circulation All surgeries were performed using a Terumo® Advanced Perfusion System 1 (Terumo Cardiovascular Systems, Ann Arbor, MI, USA). The extracorporeal circuit included a venous hard-shell cardiotomy reservoir (Maquet, Wayne, NJ, USA), a roller pump system and a membrane oxygenator (Quadrox® oxygenator Maquet, Wayne, NJ, USA) equipped with a heat exchanger and an arterial filter. The non-heparin coated system was primed with a crystalloid solution (Jonosteril®, Fresenius, Bad Homburg, Germany) and 10 000 U of heparin. Conventional cardiopulmonary bypass Blood from the right atrium was drained through the venous line, passively filling the venous cardiotomy reservoir and the following membrane oxygenator by using the hydrostatic pressure gradient. Here, it was saturated with oxygen and desaturated from carbon dioxide. Passing through the arterial pump, the blood then returned to the patient through the arterial cannula. Additional roller pumps were used for the left ventricular vent and the cardiotomy suction, both joining the venous cardiotomy reservoir. Retrograde autologous priming In the RAP group, the CPB circuit was initially primed with the same volume and consistency of fluid as the cCPB group. The only structural difference from the cCPB system was a recirculation bag as shown in Fig. 1. Before and while performing the RAP procedure, a minimum systolic blood pressure of ∼90 mmHg was maintained, if necessary with short-term administrations of vasopressors (Noradrenalin). This administration was implemented in mutual consultation with the perfusionist and anaesthetist. Before CPB initiation, the fluid from the arterial line was drained into the recirculation bag by displacing priming solution with the patient’s blood from the aorta by using arterial pressure. After the arterial line was clamped, the occlusion clamp on the venous line was released to slowly replace the crystalloid fluid with the patient’s blood using the hydrostatic pressure gradient. If any risks for the patient emerged or high amounts of vasopressors were necessary to perform RAP, further fluid displacements were consensually refrained from. In our study, patients with RAP procedures reaching fluid displacements of more than 200 ml were included. Figure 1: View largeDownload slide Scheme of the retrograde autologous priming technique. Figure 1: View largeDownload slide Scheme of the retrograde autologous priming technique. After the RAP procedure was performed, the recirculation bag remained connected to the venous reservoir, so that crystalloid volume could be administered during CPB upon haemodynamic requirements. The RAP procedure required ∼2–3 min. Surgical strategy Anaesthesia Sufentanil citrate and etomidate were used for anaesthetic induction and sufentanil citrate and either isoflurane or sevoflurane for maintenance. Anticoagulation for CPB was achieved with initially 400 U/kg heparin, and the activated clotting time was kept over 480 s during CPB. After CPB, the heparin was 100% antagonized with protamine. One gram of tranexamic acid was administered at the end of the operation according to the standard protocol at our clinic. Surgical management All operations were performed by experienced surgeons. Access was achieved via complete median sternotomy, followed by full heparinization, selection of the arterial cannulation site (either the proximal aortic arch or the distal ascending aorta) and cannulation of the right atrium with a 2-stage venous cannula. After transition to extracorporeal circulation, a mean minimal rectal temperature of 32.89°C (cCPB) and 32.55°C (RAP) was achieved. Following standard protocol at our institution, myocardial protection was accomplished with 2000 ml antegrade cold cardioplegic solution (Custodiol® HTK Bretschneider, Dr. Franz Kohler Chemie GmbH, Bensheim, Germany), which was administered over 6 min. The surgical procedures did not differ significantly between the 2 groups. A haemofilter was connected after the arterial pump as bypass. The filtration rate was dependent on the current flow rate, which was approximately 400–500 ml/min. Haemofiltration was contained during surgery in both groups. Postoperative care All patients were transferred to the cardio-surgical intensive care unit (ICU) after surgery. Sedation was performed with propofol and sufentanil citrate. Early extubation and transfer to the intermediate care unit were attempted in all cases. Transfusion criteria conformed to the ‘Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives’ (4th revised edition) by the German Medical Association [15]. As per the guidelines, the indication for RBC transfusion was Hb <8 g/dl, as all cardiac surgery patients have limited compensation capabilities. Criteria for transfusion were the same in both patient groups. According to the Guidelines, in acquired platelet aggregation disorders leading to microvascular bleeding (e.g. after cardiopulmonary bypass), transfusion triggers cannot be based on platelet counts, but rather on the clinical disposition to bleeding and is recommended until haemostasis is achieved [15]. Therefore, the decision for a platelet or plasma transfusion was in all cases a clinical one made by the responsible surgeon. Statistical analysis Statistical analysis was performed using IBM SPSS statistics 23. Categorical data are presented as numbers and percentages. Differences were explored with the χ2 test or the Fisher’s exact tests when the number of expected frequencies in a cell was <5. Continuous data were reported as mean ± standard deviation or median and interquartile range. When normal distribution was assumed, the independent t-test was applied and the Mann–Whitney U-test when normal distribution was not assumed. Statistical significance was considered at P-value <0.05. To reduce potential selection bias due to possible structural differences within the retrospective collective, we additionally performed inverse probability weighting using propensity score. For the score model, we used the following variables: age, sex, body mass index (BMI), EUROSCORE II and hypertension. RESULTS The profile of the patient population is shown in Table 1, which summarizes the demographic data and comorbidities. The 2 groups were comparable in height, weight, age, gender and BMI. There was also an equivalent incidence for comorbidities and similar heart surgery-specific risk factors. Intraoperative data are presented in Table 2. The study groups were compared in terms of the surgical procedure for aortic replacement and the number of concurrent coronary bypass operations. Average aortic cross-clamp time, reperfusion time and total CPB time, as well as the achieved mean minimal rectal temperature, were also similar in both groups. Regarding the amount of priming volume, a significant difference was observed (P < 0.001). In the RAP group, the priming fluid was reduced to a mean volume of 661.7 ± 204.9 ml compared to 1610.7 ± 310.2 ml in the cCPB group. The CPB balance at the end of the surgery was −133.2 ± 1401 ml for the cCPB group and 76.60 ± 1014 ml for the RAP group, which means that even though on average more volume was filtered out the blood consumption was higher in the cCPB group. To assess the influence of priming volume on haemodilution, Hb values were used as an indicator. The Hb level development is shown in Fig. 2A. Intraoperative measurements were taken before CPB initiation and every 30 min during CPB. The subsequent Hb measurements were taken directly after the patient’s transfer to ICU, as well as 6, 12, 24 and 48 h postoperative. Mean preoperative Hb values were 12.99 ± 1.43 mg/dl in the RAP group and 12.66 ± 1.5 mg/dl in the cCPB group (P = 0.218). Thirty minutes after CPB initiation, a notable greater decline of Hb levels was monitored in the cCPB group (8.95 ± 1.7 mg/dl vs 10.55 ± 1.61 mg/dl, P < 0.001). This decline resulted in higher requirements for intraoperative RBC transfusion for the cCPB group, as 53.3% of these patients received RBC transfusion in contrast to 36.7% of the patients in the RAP group. RBC numbers and other blood products are summarized in Table 3. Mean intraoperative RBC numbers of 1.97 ± 2.43 in the cCPB and 0.87 ± 1.33 in the RAP group (P = 0.013), as well as postoperative numbers of 1.32 ± 1.82 in the cCPB group vs 0.57 ± 1.4 in the RAP group (P = 0.002), were transfused. In summary, 70% of cCPB patients received RBC transfusion vs 48% in the RAP group. As for the other blood products, the need for platelet concentrates was comparable between the 2 groups. FFP requirements were shown to be significantly lower (P = 0.036) in the RAP group regarding the need for transfusion on ICU. The intraoperatively transfused FFP numbers, however, were similar in both groups (P = 0.437). Table 3: Transfusion of blood components cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a a Mann–Whitney U-test. b χ2 test. c CPB: conventional cardiopulmonary bypass; FFP: fresh frozen plasma; ICU: intensive care unit; IQR: interquartile range; PC: platelet concentrates; RAP: retrograde autologous priming; RBC: red blood cell; SD: standard deviation. Table 3: Transfusion of blood components cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a cCPB (n = 60) RAP (n = 60) Means ± SD Median (IQR) Means ± SD Median (IQR) P-value RBC intraoperative 1.97 ± 2.43 1.50 (0–3.75) 0.87 ± 1.53 0 (0–2.00) 0.013a RBC ICU 1.32 ± 1.82 0 (0–2.00) 0.57 ± 1.40 0 (0–0) 0.002a RBC total 3.28 ± 3.52 2.00 (0–5.00) 1.43 ± 2.00 0 (0–2.00) 0.002a Patients RBC transfused, n (%) 42 (70) 29 (48) 0.016b FFP intraoperative 2.60 ± 2.55 4.00 (0–4.00) 2.18 ± 2.60 0 (0–4.75) 0.437a FFP ICU 1.48 ± 3.32 0 (0–1.5) 0.52 ± 1.63 0 (0–0) 0.036a FFP total 4.08 ± 4.48 4.00 (0–5.75) 2.70 ± 3.01 1.00 (0–6.00) 0.236a PC intraoperative 0.40 ± 0.62 0 (0–1.00) 0.50 ± 0.79 0 (0–1.00) 0.790a PC ICU 0.18 ± 0.54 0 (0–0) 0.10 ± 0.40 0 (0–0) 0.340a PC total 0.58 ± 0.93 0 (0–1.00) 0.60  ±  0.83 0 (0–1.00) 0.761a a Mann–Whitney U-test. b χ2 test. c CPB: conventional cardiopulmonary bypass; FFP: fresh frozen plasma; ICU: intensive care unit; IQR: interquartile range; PC: platelet concentrates; RAP: retrograde autologous priming; RBC: red blood cell; SD: standard deviation. Figure 2: View largeDownload slide Laboratory values at various points in time comparing the cCPB group and the RAP group. (A) Haemoglobin levels (g/dl); (B) lactate levels (mmol/l); (C) creatinine kinase levels (U/l); (D) troponin levels (ng/ml). CPB: cardiopulmonary bypass; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; Pre-Op: preoperative; Post-Op: postoperative; RAP: retrograde autologous priming. Figure 2: View largeDownload slide Laboratory values at various points in time comparing the cCPB group and the RAP group. (A) Haemoglobin levels (g/dl); (B) lactate levels (mmol/l); (C) creatinine kinase levels (U/l); (D) troponin levels (ng/ml). CPB: cardiopulmonary bypass; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; Pre-Op: preoperative; Post-Op: postoperative; RAP: retrograde autologous priming. The pH and lactate values were concurrently measured with the Hb levels by blood gas analysis before CPB initiation, during CPB and until 24 h postoperative. In addition, the maximum lactate on ICU, as well as the lowest pH on ICU, was determined. The lactate development is demonstrated in Fig. 2B, illustrating a higher increase in postoperative lactate levels in the cCPB group compared to the RAP group, with a mean maximum lactate of 3.33 ± 2.25 mmol/l in the cCPB group vs 2.71 ± 1.25 mmol/l in the RAP group (P = 0.053). Consistent with the difference in lactate increase, the mean minimum pH level on ICU showed lower values in the cCPB group (P = 0.018). Troponin and creatine kinase levels were measured preoperatively and postoperatively, as well as on first, second and third postoperative days. The course of creatine kinase values is demonstrated in Fig. 2C. Coming from initially lower baseline values on the cCPB side, the course shows a change to slightly higher postoperative measurements for the cCPB group compared to the RAP group. The development of troponin values is illustrated in Fig. 2D. The troponin levels show a mild tendency to increased values in the cCPB group. Parameters for kidney function, urea and creatinine levels were monitored preoperatively and postoperatively and on first, second and third postoperative days. Both urea and creatinine values were comparable between the groups. Concurrent measurements were made for bilirubin, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase, which showed no notable difference either. The course of leucocyte levels was also independent of the perfusion method. Preoperative platelet levels showed a non-significant difference between the 2 groups. In the postoperative development, however, a tendency to decreased platelet levels after transfer to ICU (126.7 × 10³/µl cCPB vs 140.3 × 10³/µl RAP, P = 0.018), as well as on the first postoperative day (144.0 × 10³/µl cCPB vs 159.1 × 10³/µl RAP, P = 0.027), was observed. The possible impact of postoperative haemodilution on the Hb levels and consequential transfusion was considered by calculating the total fluid balance on ICU after 6, 12 and 24 h. The fluid balance was comparable at all points of the calculation. At the end point of calculation after 24 h, the total fluid balance amounted to +3469 ± 2064 ml in the cCPB group and +3244 ± 1652 ml in the RAP group (P = 0.717). Furthermore, drainage loss was also measured after 6, 12 and 24 h and is demonstrated in Fig. 3. A statistically significant difference in drainage loss after 6 h (490.6 ± 414.4 ml for cCPB vs 295.9 ± 342.6 ml for RAP, P ≤ 0.001), as well as after 12 h (652.1 ± 463.9 ml for cCPB vs 450.1 ± 415.5 ml for RAP, P < 0.001) and after 24 h (866.4 ± 508.4 ml for cCPB vs 693.1 ± 483.9 ml for RAP, P = 0.004), was observed. Figure 3: View largeDownload slide Postoperative drainage loss over the course of time (ml). cCPB: conventional cardiopulmonary bypass; Post-Op: postoperative; RAP: retrograde autologous priming. Figure 3: View largeDownload slide Postoperative drainage loss over the course of time (ml). cCPB: conventional cardiopulmonary bypass; Post-Op: postoperative; RAP: retrograde autologous priming. The postoperative development was measured by length of the ICU stay, ventilation time und overall hospital stay and revealed no statistically relevant differences. Complications on ICU such as occurrence of bleeding, infections, pleural effusion, kidney failure and cardiac arrhythmias were unaffected by the perfusion strategy. A mild tendency towards reduced neurological outcome was shown, as 14 cases of delirium and 1 incidence of stroke occurred in the cCPB group compared to slightly lower numbers of 10 cases of delirium and no stroke incidence in the RAP group. Cases of death did not occur at all. The clinical outcome is shown in Table 4 in detail. Table 4: Clinical outcome cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b χ2 test. c Fisher’s exact test. ARF: acute renal failure; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; RAP: retrograde autologous priming. Table 4: Clinical outcome cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b cCPB (n = 60) RAP (n = 60) P-value ICU stay (h) 54.47 ± 46.38 52.62 ± 44.66 0.699a Hospital stay (days) 11.59 ± 5.98 10.90 ± 5.25 0.625a Ventilation time (h) 17.78 ± 17.49 14.07 ± 8.01 0.444a Delirium 14 (23.3) 10 (16.7) 0.361b Infection 9 (15.0) 8 (13.3) 0.793b Bleeding 4 (6.7) 0 (0) 0.119c Stroke 1 (1.7) 0 (0) 1.000c ARF 2 (3.3) 0 (0) 0.496c Cardiac arrhythmias 15 (25.0) 18 (30.0) 0.540b Pleural effusion 10 (16.7) 9 (15.0) 0.803b Values are expressed as means ± standard deviation or patient numbers (%). a Mann–Whitney U-test. b χ2 test. c Fisher’s exact test. ARF: acute renal failure; cCPB: conventional cardiopulmonary bypass; ICU: intensive care unit; RAP: retrograde autologous priming. DISCUSSION Extracorporeal circulation is still commonly used in cardiac surgery and requires crystalloid priming, which is known to cause haemodilution. In consequence, it results in lower intraoperative Hb levels, which may negatively influence the tissue oxygen delivery, as well as reduction of plasma colloid osmotic pressure and decreased concentration of coagulation factors and platelets. It is documented that severe haemodilution on cCPB is associated with dilutional coagulopathy, bleeding and thrombosis-associated worse outcomes [16]. Furthermore, studies have found a direct association between the nadir haematocrit during CPB and the most major complications during cardiac surgery [17]. The purpose of this study was to explore the effects of RAP during elective TAA surgery on reducing RBC transfusion requirements and other beneficial effects of decreased haemodilution during CPB. By reducing the priming volume to 662 vs 1611 ml (P < 0.001) through RAP, the Hb drop during CPB was significantly decreased (P < 0.001). This fact resulted in a lower need for RBC transfusion in the RAP group. Patients receiving surgery under cCPB had an overall need for transfusion in 70% of the cases. In comparison, only 48.3% of the patients undergoing the RAP procedure received RBC transfusion at all during the entire hospital stay. Furthermore, increased lactate levels (P = 0.053) with concurrent lower pH levels on ICU were monitored in the cCPB group. Both issues can be induced through hypoxia, and the findings allow the conclusion that higher haemodilution during cCPB results in poorer oxygen delivery. Ranucci et al. confirmed the role of early hyperlactataemia as a predictive marker of bad outcomes in cardiac surgery and also indicated haemodilution on CPB as an independent determinant of moderate and severe early postoperative hyperlactataemia [18]. Other studies concurred with these findings and therefore concluded that reduction of haemodilution improves microcirculation perfusion [10]. Other results in this study highlight that CPB-induced haemodilution does affect not only anaemia-related RBC transfusion but also coagulation, postoperative bleeding and FFP requirements. Ranucci et al. [16] recently published an extensive in vivo study, demonstrating the tendency towards coagulopathy in patients with severe haemodilution after cardiopulmonary bypass and showing a decrease in fibrinogen levels in their patients after transfer to ICU, which was proven to be haemodilution related. Our patient population that received a greater volume of crystalloid solution through cCPB showed a greater need for FFP transfusion on ICU, despite intraoperative haemofiltration. Within this implemented retrospective study, coagulopathy-related laboratory values were not recorded routinely for all patients. We can assume that intraoperative haemodilution plays a part in the development of microvascular bleeding after cardiopulmonary bypass. Nevertheless, one can speculate that a primary lower haemodilution due to RAP may have an overall positive impact on the coagulation. Furthermore, there was a significantly higher drainage loss on ICU for the cCPB patients. A possible reason for the elevated drainage loss within the first hours could be coagulopathy-related microvascular bleeding which is suspended after transfusion-induced optimization. Although relevant measurements were not recorded, based on the aforementioned data, one can speculate that the increase of FFP requirements and drainage loss in the cCPB group is caused by haemodilution-related coagulopathy. The greater loss of drainage fluid could also explain the differences in RBC requirements regarding the postoperative period exclusively. In the cCPB group, 47% of the patients had the need for RBC transfusion on ICU vs only 20% in the RAP group. As both within our study as well as in the mentioned studies haemodilution is identified as a cause for an increased need for transfusion during cardiac surgery—against the background of a general shortage of blood products—efforts should be made to reduce this effect. In addition to the use of smaller, patient-adjusted, CPB sets with a per se lower priming volume, RAP can have an additional beneficial effect on transfusion requirements. Furthermore, this beneficial effect can be strengthened by the usage of blood cardioplegia or a higher intraoperative filtration rate. Other studies have outlined the need for transfusion as an independent risk factor for acute kidney injury after surgery on the thoracic aorta [19]. Despite these findings, the creatinine development and incidence of acute kidney injury in our study was independent of the perfusion strategy and transfusion rates. Creatine kinase and troponin levels were also not appreciably affected by the perfusion strategy, although a trend to slightly reduced cardiac markers was observed in the RAP group. Even though the postoperative platelet development showed a statistically significant difference between the groups, the minimal clinical difference is not presumed to have any beneficial impact for the RAP patients. The RAP procedure had no adverse influence on aortic cross-clamp time, reperfusion time and total CPB time, as no prolonged CPB duration was observed. Many studies have evaluated the various negative effects of RBC transfusion on the patient’s long-term and short-term outcome such as pneumonia, nosocomial infections, acute renal failure, prolonged hospital stay and increased postoperative morbidity and mortality [1–6]. Despite the differences in RBC transfusion between our study groups, there were no consequential differences in postoperative complications or outcome. Other studies investigating RAP come to similar results. A meta-analysis on the effects of RAP by Sun et al. including ten randomized controlled trials summarized that RAP could reduce transfusion in adults significantly but had no effect on clinical outcomes [12]. Although there were no statistically relevant differences in the neurological outcome, a certain trend to reduced delirium was observed. Limitations Our study has several limitations. Firstly, this study is a retrospective single-centre study. Secondly, due to the nature of this study, selection bias cannot be excluded. Thirdly, the results show significant differences between RAP and cCPB. However, the reasons for some of these differences can only be speculatively explained based on existing literature. Proper validation is only possible within a larger scale, prospective, randomized study. CONCLUSIONS In summary, we were able to show that RAP is a safe method to reduce RBC transfusion in TAA surgery without any adverse effects on the clinical outcome. Furthermore, it could be shown that the usage of RAP has a positive effect on the need for FFP and the postoperative drainage loss. Due to lower lactate values when using RAP compared to cCPB, an improved microcirculation caused by less haemodilution can be suspected. Against the background of a general shortage of blood products, complications caused by transfusions and consequently higher costs, all possibilities to reduce the need for transfusion should be exploited. As a consequence of our results, we have implemented RAP as an important component of our patient blood management concept also as clinical standard in aortic surgery. Conflict of interest: none declared. REFERENCES 1 Horvath KA , Acker MA , Chang H , Bagiella E , Smith PK , Iribarne A et al. Blood transfusion and infection after cardiac surgery . Ann Thorac Surg 2013 ; 95 : 2194 – 201 . Google Scholar Crossref Search ADS PubMed 2 Likosky DS , Paone G , Zhang M , Rogers MAM , Harrington SD , Theurer PF et al. Red blood cell transfusions impact pneumonia rates after coronary artery bypass grafting . Ann Thorac Surg 2015 ; 100 : 794 – 800 ; discussion 801. Google Scholar Crossref Search ADS PubMed 3 Galas FRBG , Almeida JP , Fukushima JT , Osawa EA , Nakamura RE , Silva CMPDC et al. Blood transfusion in cardiac surgery is a risk factor for increased hospital length of stay in adult patients . J Cardiothorac Surg 2013 ; 8 : 54 . Google Scholar Crossref Search ADS PubMed 4 Taylor RW , O’Brien J , Trottier SJ , Manganaro L , Cytron M , Lesko MF et al. Red blood cell transfusions and nosocomial infections in critically ill patients . Crit Care Med 2006 ; 34 : 2302 – 8 ; quiz 2309. Google Scholar Crossref Search ADS PubMed 5 Koch CG , Li L , Duncan AI , Mihaljevic T , Loop FD , Starr NJ et al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival . Ann Thorac Surg 2006 ; 81 : 1650 – 7 . Google Scholar Crossref Search ADS PubMed 6 Engoren MC , Habib RH , Zacharias A , Schwann TA , Riordan CJ , Durham SJ. Effect of blood transfusion on long-term survival after cardiac operation . Ann Thorac Surg 2002 ; 74 : 1180 – 6 . Google Scholar Crossref Search ADS PubMed 7 Rosengart TK , DeBois W , O’Hara M , Helm R , Gomez M , Lang SJ et al. Retrograde autologous priming for cardiopulmonary bypass: a safe and effective means of decreasing hemodilution and transfusion requirements . J Thorac Cardiovasc Surg 1998 ; 115 : 426 – 39 . Google Scholar Crossref Search ADS PubMed 8 Trapp C , Schiller W , Mellert F , Halbe M , Lorenzen H , Welz A et al. Retrograde autologous priming as a safe and easy method to reduce hemodilution and transfusion requirements during cardiac surgery . Thorac Cardiovasc Surg 2015 ; 63 : 628 – 34 . Google Scholar Crossref Search ADS PubMed 9 Balachandran S , Cross MH , Karthikeyan S , Mulpur A , Hansbro SD , Hobson P. Retrograde autologous priming of the cardiopulmonary bypass circuit reduces blood transfusion after coronary artery surgery . Ann Thorac Surg 2002 ; 73 : 1912 – 8 . Google Scholar Crossref Search ADS PubMed 10 Cheng M , Li J-Q , Wu T-C , Tian W-C. Short-term effects and safety analysis of retrograde autologous blood priming for cardiopulmonary bypass in patients with cardiac valve replacement surgery . Cell Biochem Biophys 2015 ; 73 : 441 – 6 . 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Interact CardioVasc Thorac Surg 2013 ; 16 : 778 – 83 . Google Scholar Crossref Search ADS PubMed 15 Bundesärztekammer . Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivates . 4th edn . Freiburg im Breisgau : Karger S , 2009 . 16 Ranucci M , Baryshnikova E , Ciotti E , Ranucci M , Silvetti S. Hemodilution on cardiopulmonary bypass: thromboelastography patterns and coagulation-related outcomes . J Cardiothorac Vasc Anesth 2017 ; 31 : 1588 – 94 . Google Scholar Crossref Search ADS PubMed 17 Habib RH , Zacharias A , Schwann TA , Riordan CJ , Durham SJ , Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg 2003 ; 125 : 1438 – 50 . Google Scholar Crossref Search ADS PubMed 18 Ranucci M , Carboni G , Cotza M , Bianchi P , Di Dedda U , Aloisio T. Hemodilution on cardiopulmonary bypass as a determinant of early postoperative hyperlactatemia . PloS One 2015 ; 10 : e0126939. Google Scholar Crossref Search ADS PubMed 19 Kim WH , Park MH , Kim H-J , Lim H-Y , Shim HS , Sohn J-T et al. Potentially modifiable risk factors for acute kidney injury after surgery on the thoracic aorta: a propensity score matched case-control study . Medicine (Baltimore) 2015 ; 94 : e273. Google Scholar Crossref Search ADS PubMed © The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

Interactive CardioVascular and Thoracic SurgeryOxford University Press

Published: Feb 4, 2019

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