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Effects of Cardiopulmonary Bypass Circuit Shortening on Transfusion Reduction: A Retrospective Cohort Study in the Cardiac Surgery Patients

AUTHORS

Kivanc Atilgan 1 , * , Ertan Demirdas 2

AUTHORS INFORMATION

1 TOBB ETU Hospital, Cardiovascular Surgery Department, Ankara, Turkey

2 Cardiovascular Surgery Department, Medicine Faculty, Bozok University, Yozgat, Turkey

How to Cite: Atilgan K, Demirdas E. Effects of Cardiopulmonary Bypass Circuit Shortening on Transfusion Reduction: A Retrospective Cohort Study in the Cardiac Surgery Patients, Iran Red Crescent Med J. 2019 ; 21(7):e83528. doi: 10.5812/ircmj.83528.

ARTICLE INFORMATION

Iranian Red Crescent Medical Journal: 21 (7); e83528
Published Online: July 27, 2019
Article Type: Research Article
Received: August 21, 2018
Revised: June 6, 2019
Accepted: June 9, 2019
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Abstract

Background: Hemodilution anemia, due to the use of crystalloid liquids during the preparation of cardiopulmonary bypass (CPB) circuits, results in the increased number of RBC, which may lead to hemolysis, acute pulmonary injury, allergic reactions, metabolic and coagulative abnormalities, volume overload, alloimmunization, immunosuppression, graft versus host reaction, and a remarkable increase in hospitalization costs.

Objectives: The present study aimed to evaluate the effects of shortened cardiopulmonary bypass circuits on the blood salvage process in patients undergoing cardiac surgery with cardiopulmonary bypass and determine the cutoff BSA value for effectiveness.

Methods: A retrospective cohort study was performed in a private hospital, Ankara, Turkey, between January 2011 and November 2015 to assess 235 patients having a CPB with shortened circuits. The control group comprised 240 patients who underwent cardiac surgery utilizing a standard extracorporeal circulation circuit at our institution. In the case group, to achieve a low-priming volume, the CPB circuit was shortened and CPB console was positioned as close as possible to the operative field. The arterial line (3/8”) and the venous line (1/2) were 80 cm and 90 cm, respectively, shorter in the case group than in the control group. Patient data were collected by retrospective medical chart review.

Results: Intraoperative red blood cell (RBC) transfusion amount was 465 ± 141.5 mL in the case group and 722.5 ± 285.4 mL in the control group (P < 0.001). Postoperative RBC transfusion was 418.7 ± 198.1 mL in the case group and 628.7 ± 452.3 mL in the control group (P < 0.001). The total amount of RBC transfusion was 742.4 ± 228.7 mL in the case group and 1012.3 ± 625.5 mL in the control group (P < 0.001). ROC analysis showed that shortening the CPB circuits was effective in patients with a BSA of < 1.67 (AUC = 0.84; P < 0.001)

Conclusions: Shortening of the CPB circuit could be helpful to avoid severe hemodilution and to reduce RBC use in small adult patients (with BSA < 1.67) undergoing cardiac surgery with cardiopulmonary bypass.

Keywords

Blood Salvage Blood Transfusion Cardiac Surgery Cardiopulmonary Bypass Crystalloid Solutions Erythrocytes Heart-Lung Machine Hemodilution Hemolysis Isotonic Solutions

Copyright © 2019, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited

1. Background

Hemodilutional anemia is observed in patients due to the use of crystalloid liquids during the preparation of cardiopulmonary bypass (CPB) circuits (1-7). Preoperative blood volume, hematocrit (Hct), and the amount of crystalloid liquids are the main factors determining the level of hemodilution, a situation that causes a reasonable need for intra/postoperative red blood cell (RBC) transfusion (8-11). About 30% - 80% of the patients undergoing open-heart surgery need an allogeneic blood transfusion (1-7).

The increased number of RBC transfusions would lead to transfusion complications such as plasma and erythrocyte hemolysis, acute pulmonary injury, allergic reactions, metabolic and coagulative abnormalities, volume overload, alloimmunization, immunosuppression, ferrum overload, graft versus host reaction, and a remarkable increase in hospitalization costs (12). Furthermore, severe hemodilution during CPB is implicated as an independent risk factor for perioperative morbidity and mortality (13).

For the last couple of years, to eliminate the risks, blood salvage techniques have been an important issue in cardiac surgery. Shortening the CPB circuits is a technique proposed to avoid transfusion and transfusion complications (14).

2. Objectives

The present study aimed to evaluate the effects of shortened CPB circuits on the blood salvage process in patients undergoing cardiac surgery with cardiopulmonary bypass and determine the cut-off BSA value for effectiveness.

3. Methods

3.1. Patients

A retrospective cohort study was designed according to the principles of the Declaration of Helsinki and approved by the Local Ethics Committee of Private Lokman Hekim Akay Hospital, Ankara, Turkey, with code “2016-1344” on 14/12/2016. The decision for surgical revascularization was based on the ESC/EACTS guidelines on myocardial revascularization. We retrospectively reviewed the clinical records of patients who underwent open-heart surgery with CPB in Akay Hospital, Ankara, Turkey, between January 2011 and November 2015.

The exclusion criteria were as follows: (1) redo procedures, (2) patients on anticoagulant and antiaggregants, (3) emergency/urgent surgery, (4) patients with renal failure (creatinine > 2.0 mg/dL), (5) patients who had ultrafiltration during CPB, (6) intraoperative acute blood loss, and (7) the need for hypothermic circulatory arrest.

After applying the inclusion and exclusion criteria, 141 patients were excluded, and 235 patients having CPB with shortened circuits were included in the study. The control group comprised 240 patients who underwent cardiac surgery utilizing a standard extracorporeal circulation circuit at our institution. Patient data were collected by retrospective medical chart review.

3.2. Standard CPB Circuit Design

The extracorporeal circuit consisted of a standard CPB tubing pack, an arterial filter, and an adult oxygenator mounted on a roller pump base incorporating a heater-cooler unit (Eurosets Perfusion Tubing Set and Eurosets Horizon Oxygenator Set). We used a 22F arterial cannula and a 36F two-stage venous cannula for arterial and venous cannulation in coronary artery bypass grafting and aortic valve surgery, as well as two 34F cannulas for venous cannulation in mitral and tricuspid valve surgeries. In the control group, the prime volume was prepared with 1000 mL of Isolyte S, 500 mL of Ringer Lactate, 150 mL of Mannitol, 5000 Unites of Heparin, and 1 g of Cefazolin. At the end of the CPB, heparin was neutralized by protamine and the blood remaining in the oxygenator was transfused to the patient.

3.3. CPB Circuit Design of the Case Group

The entire CPB console was positioned as close as possible to the operative field to make the short tubing connections possible. The CPB circuit was shortened to achieve a low-priming volume. The arterial line (3/8”) was 180 cm in the control group and 100 cm in the case group; the venous line (1/2) was 150 cm in the control group and 60 cm in the case group (Figure 1). The priming volume of the tubes was calculated as πr2h, where h is the length of the tubing and r is the tubing radius. For 3/8-inch tubes, a volume of 0.346 mL was calculated per every 1 cm of the tube and for ½-inch tubes, a volume of 0.622 mL was calculated for every 1 cm of the tube. In the case group, the prime volume consisted of 650 mL of Isolyte S, 300 mL of Ringer Lactate, 150 mL of Mannitol, 5000 Unites of Heparin, 1 g of Cefazolin.

Intraoperative image of a patient undergoing CABG with shortened CPB circuit system
Figure 1. Intraoperative image of a patient undergoing CABG with shortened CPB circuit system

The main RBC transfusion criteria were an Hgb level of below 6.5 g/dL or the Hct level of below 20% during CPB and the Hgb level of below 7 g/dL and the Hct level of below 21% for the postoperative period.

3.4. Cardioplegia Protocol

Cardiac arrest was established by cold crystalloid (Plegisol) antegrade/retrograde cardioplegia. The maintenance of arrest was achieved with cold blood cardioplegia infused in an antegrade/retrograde fashion. Cardioplegia administration was repeated every 20 minutes. Moderate hypothermia (28°C) was used in all patients.

3.5. Statistical Analysis

Statistical analysis was conducted using the SPSS Statistics for Windows, version 17.0 (SPSS Inc., Chicago, Ill., USA). All variables were investigated using visual (histograms and probability plots) and analytical methods (Kolmogorov-Smirnov test) to determine the normality of distribution. Continuous variables are reported as means and standard deviations for normally distributed variables and as medians and the interquartile range for non-normally distributed variables. Categorical variables are presented as numbers and percentages. Comparisons between groups were made using the chi-square test for qualitative variables, the independent t-test for normally distributed continuous variables, and the Mann Whitney U test for non-normally distributed continuous variables. Receiver operating characteristics (ROC) analysis was performed to evaluate the cutoff BSA value at which the shortened CBP circuits were effective. The area under the curve (AUC) was calculated as a measure of test accuracy. Sensitivity and specificity were presented when a significant cutoff value was observed. P values of < 0.05 were considered significant.

4. Results

The mean age was 65.5 ± 8.8 in the case group and 59.7 ± 10.1 in the control group (P = 0.003). Sex, BSA, and preoperative Hgb parameters did not remark any statistical difference between the two groups. Preoperative EF was 40% (35% - 60%) in the case group and 60% (55% - 65%) in the control group (P < 0.001). In the case group, 105 of the patients had a history of myocardial infarction one month preoperatively, but only 40 patients in the control group had such a history (P < 0.001) (Table 1).

Table 1. Demographic Data of Patients
Case GroupControl GroupP Value
Female/Male65/17056/1840.6
Age, y65.5 ± 8.859.7 ± 10.10.003
BMI, kg/m229.1 ± 4.129.9 ± 4.70.4
Preoperative Hb g/dL14.1 ± 1.714.08 ± 1.60.9
Preoperative Hct, %42.4 ± 4.642.6 ± 50.8
Preoperative EF, %, median (IQR)40 (35 - 60)60 (55 - 65)< 0.001
History of AMI in the last month10540< 0.001
HT, No. (%)20 (43.5)31 (52.5)0.36
DM, No. (%)15 (32.6)32 (54.2)0.03
CRF, No. (%)1 (2.2)00.4
COPD, No. (%)14 (30.4)14 (23.7)0.44
History of CVA, No. (%)1 (2.2)3 (5.1)0.4
History of non-cardiac surgery, No. (%)1 (2.2)00.4
Preoperative LFT abnormalities (AST), No. (%)1 (2.2)00.4
Preoperative anemia, No. (%)1 (2.2)1 (1.7)0.9
Arteritis, No. (%)1 (2.2)00.4

Abbreviations: BMI, body mass index; CRF, chronic renal failure; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; DM: diabetes mellitus EF, ejection fraction; Hct: hematocrit; Hgb: hemoglobin; HT: hypertension; LFT: liver function Test; MI: myocardial infarction.

There were 32 patients with a history of diabetes mellitus in the control group and 15 patients in the case group (P = 0.03). The case and control groups were similar in CPB, X-clamp, the total operation time, activated coagulation time (ACT), the maximum intraoperative Hct level, and the maximum Hct level during CPB. The mean prime volume was 1079 ± 190.8 mL in the case group and 1793.2 ± 398.1 mL in the control group (P < 0.001). The minimum intraoperative Hct level was 22.7 ± 2.5% in the control group and 23.8 ± 1.8% in the case group (P = 0.02) (Table 2).

Table 2. Intraoperative Data
Case GroupControl GroupP Value
Operation
CABGX110110.9
CABGX216190.7
CABGX365620.8
CABGX474760.8
CABGX543450.7
CABGX6650.9
CEA+CABG870.6
AVR+CABG540.5
MVR+CABG690.4
AVR+MVR+CABG22
CPB time, min, median (IQR)64.5 (55 - 80.25)60 (53 - 72)0.2
X-clamp time, min, median (IQR)45.5 (38.7 - 55.2)44 (34 - 51)0.3
Total operation time, min, median (IQR)190 (180 - 222.5)180 (170 - 230)0.4
Prime volume, mL1079 ± 190.81793.2 ± 398.1< 0.001
İntraoperative ACT, median (IQR)678 (582 - 831.5)649 (584 - 746)0.3
İntraoperative minimum Hct, %22.7 ± 2.523.8 ± 1.80.02
İntraoperative maximum Hct, %35.9 ± 4.234.7 ± 2.60.07
Minimum Hct during CPB, %22.7 ± 2.523.8 ± 1.80.02
Maximum Hct during CPB, %24.9 ± 1.825.4 ± 1.80.6

Abbreviations: ACT, activated clotting time; AVR, aortic valve replacement; CABG, coronary artery bypass graft; CEA, carotid endarterectomy; CPB, cardiopulmonary bypass; Hct, hematocrit; MVR, mitral valve replacement.

In-hospital mortality, two-month mortality, positive inotropic drug treatment (PIDT) and IABP treatments in intensive care unit (ICU), the duration of ICU and total hospital stay, and urine output 24 hours postoperatively were similar in both groups (P > 0.05). The extubation time was 8.1 ± 3.2 hours in the control group and 7 ± 1.8 hours in the case group (P = 0.02) (Table 3).

Table 3. The Amount of RBC Products Used and Postoperative Data
Case GroupControl GroupP Value
İntraoperative need for RBC, No. (%)10 (21.7)40 (67.8)< 0.001
Intraoperative amount of RBC products, mL465 ± 141.5722.5 ± 285.4< 0.001
Postoperative need for RBC, No. (%)8 (17.4)40 (67.8)< 0.001
Postoperative amount of RBC products, mL418.7 ± 198.1628.7 ± 452.3< 0.001
Total need for RBC, No. (%)16 (34.8)53 (89.8)< 0.001
Total amount of RBC products, mL742.4 ± 228.71012.3 ± 625.5< 0.001
Mean postoperative bleeding, median (IQR)375 (300 - 500)350 (300 - 650)0.2
In-hospital mortality, No. (%)00
Two-month mortality, No. (%)01 (0.4)0.9
Awaking time, h3.4 ± 23.2 ± 1.30.4
Extubation time, h8.1 ± 3.27 ± 1.80.02
PIDT in ICU, No. (%)7 (15.2)6 (10.2)0.4
IABP in ICU, No. (%)2 (4.3)00.1
ICU stay duration, h19.9 ± 5.220.9 ± 9.30.5
Hospital stay duration, days, median (IQR)4 (4 - 5)4 (4 - 5)0.9
CVA, No. (%)1 (2.2)00.4
Arrhythmias, No. (%)4 (8.7)7 (11.9)0.6
Cardiac tamponade, No. (%)01 (1.7)0.9
Postoperative AST increase, No. (%)5 (10.9)15 (25.4)0.06
Post-operative Urea increase, No. (%)10(21.7)16(27.1)0.5
Hct one-day post-operatively, mean ± SD30.8 ± 4.631.9 ± 3.10.8
Hct at discharge, mean ± SD28.9 ± 3.929.1 ± 2.70.9

Abbreviations: ASA, acetylsalicylic Acid; AST, aspartate aminotransferase; CVA, cerebro-vascular accident; Hct, hematocrit; IABP, intra-aortic- balloon- pump; ICU, intensive care unit; PIDT, positive inotropic drug treatment.

The amount of intraoperative red blood cell transfusion was 465 ± 141.5 mL in the case group and 722.5 ± 285.4 mL in the control group (P < 0.001). Postoperative RBC transfusion was 418.7 ± 198.1 mL in the case group and 628.7 ± 452.3 mL in the control group P < 0.001). The total amount of red blood cell transfusion was 742.4 ± 228.7 mL in the case group and 1012.3 ± 625.5 mL in the control group (P < 0.001) (Table 3). However, the median value of postoperative bleeding was 375 mL in the case group and 350 mL in the control group (P > 0.05) (Table 3). In terms of postoperative complications, no statistically significant difference was observed between the two groups (P > 0.05).

On the first day postoperatively, the Hct value was 30.8 ± 4.6% in the case group and 31.9 ± 3.1% in the control group. The last Hct value before discharge was 28.9 ± 3.9% in the case group and 29.1 ± 2.7% in the control group (P > 0.05). ROC analysis showed that shortening the CPB circuits was effective in patients with a BSA of < 1.67 (AUC = 0.84; sensitivity = 0.96, specificity = 0.64; P < 0.001) (Figure 2).

ROC curve for BSA and need for transfusion
Figure 2. ROC curve for BSA and need for transfusion

5. Discussion

Excessive hemodilution in cardiac surgery is a major risk factor for blood transfusion. It is associated with increased morbidity and mortality depending on the degree of hemodilution (1-7). Current evidence recommends the reduction of hemodilution and the preservation of Hct for the best outcomes in patients undergoing routine cardiac surgery with CPB (1-15). Hemodilution in cardiac surgery is associated with adverse outcomes that are dependent on the degree of dilution. Several studies have shown that the low Hct during CPB is an independent risk factor for morbidity and mortality in cardiac surgery. There are inverse relationships between Hct < 25% during CPB and mortality, stroke, return to CPB, the need for intra-aortic balloon pump (IABP), and inotropes (1-3). In a study, patients with Hct < 19% had a mortality rate twice as high as patients with Hct > 25% (2). The risk of acute renal failure (ARF) was found to increase as the CPB Hct fell below 24% (4, 5, 7). Another study showed that CPB Hct of below 22% increased the risk of stroke, myocardial infarction, low cardiac output, renal failure, prolonged ventilator support, pulmonary edema, and postoperative bleeding necessitating re-exploration (6).

Other blood components, such as coagulation factors and platelet numbers, are also affected by hemodilution. Furthermore, CPB may lead to the activation of coagulation factors, resulting in the consumption of coagulation factors. This process may lead to impaired hemostasis and may aggravate bleeding disorders (11, 16).

RBC transfusion is not without risk. It can lead to immunomodulation, transmission of infectious diseases, allergic reactions, hemolytic reactions, transfusion-related acute lung injury, and increased risk of infection (6, 7, 9, 10, 12, 13). Furthermore, blood transfusion has been linked to decreased short-term (1, 6, and 12 months) and long-term (5 and 10 years) survival in patients undergoing cardiac surgery (6). The risk of low output failure, defined as the need for inotropes, IABP, and return to CPB, associated with Hct < 25%, further increases with RBC transfusion (2). Blood transfusion during CPB also exacerbates ARF associated with severe hemodilution in CABG patients (4). The incidence and magnitude of RBC transfusion are also associated with the increased risk of postoperative complications and adverse events in renal, pulmonary, cardiac, and neurologic systems in CABG surgery (15).

Because anemia is associated with poor outcomes after cardiac surgery and RBC transfusion further worsens the outcomes, it is crucial to reduce hemodilutional anemia by decreasing blood transfusions. Blood salvage techniques to decrease blood product transfusion can mainly be divided into three parts as preoperative, intraoperative, and postoperative procedures. Patients with preoperative anemia can be treated with hematopoietic drugs or autologous blood transfusion in case of elective cardiac surgery indications. However, in emergent or urgent circumstances, intra/postoperative procedures may become prominent. In this case, the surgeon may choose to follow up patients with normovolemic anemia in the postoperative period (15). Autologous blood transfusion, intraoperative plasmapheresis, hemofiltration, and re-transfusion of the blood in the drainage tubes in ICUs are some of the other preoperative techniques (15).

Shortening the CPB circuits resulting in lower prime volume can reduce hemodilution and blood transfusion requirement (8, 13). Retrograde autologous priming also proved to decrease RBC transfusion (17). Cormack et al. investigated the effects of varying CPB prime volumes and autologous priming on Hct, RBC use, and outcomes in a prospective study. They showed that the decreased incidence of Hct < 20% on CPB could reduce RBC transfusion and the rate of morbidity and mortality associated with decreased CPB prime volume (18). Similar results were observed in our study. Small adults are affected more easily by even small transfusion volumes than adults with larger BSA because of having smaller total intravenous volumes. We avoided significant hemodilution and restored the hematocrit to the preoperative level after CPB weaning by minimizing tube lengths, limiting the mixing of RBCs with the priming solution, and initiating CPB while keeping a venous reservoir and a venous drainage line almost empty as possible as we could. In our study, the prime volume was 1079 ± 190.8 mL in the case group and 1793.2 ± 398.1 mL in the control group (P < 0.001) and the total amount of RBC was 742.4 ± 228.7 mL in the case group and 1012.3 ± 625.5 mL in the control group (P < 0.001). The minimum Hct levels were higher in the case group than in the control group intraoperatively (22.7 ± 2.5% vs. 23.8 ± 1.8%) and during CPB (22.7 ± 2.5% vs. 23.8 ± 1.8%) (P = 0.02). However, the two groups were similar in terms of the early postoperative parameters such as the need for PIDT and IABP in ICU, the duration of ICU and total hospital stay, cerebrovascular accident, arrhythmias, cardiac tamponade, postoperative AST, and urea increase (P > 0.5).

There were some limitations to this study. First, it utilized a retrospective design. Second, despite adjustment for as many factors as possible, we think that some confounding factors might have remained to affect the results.

5.1. Conclusions

We demonstrated that shortening the CPB circuit may reduce the RBC use in patients undergoing cardiac surgery with cardiopulmonary bypass only in adults with BSA < 1.67 (AUC = 0.84; sensitivity = 0.96, specificity = 0.64; P < 0.001). Based on our clinical experience, we strongly care to manage CPB with shortened circuits. Besides the decreased incidence of early and late preoperative complications, we can decrease a reasonable amount of fiscal charges by avoiding the frequent number of transfusions.

Footnotes

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