Novel method for estimating the total blood volume: the importance of adjustment using the ideal body weight and age for the accurate prediction of haemodilution during cardiopulmonary bypass

Novel method for estimating the total blood volume: the importance of adjustment using the ideal... Abstract OBJECTIVES Although total blood volume (TBV) is central to the estimation of the haemodilution rate during cardiopulmonary bypass (CPB), conventional formulas lack sufficient accuracy. The aim of this study was to establish a new formula using ideal body weight (BW) with adjustment for gender or age to estimate TBV for a more accurate prediction of the haemodilution rate during CPB. METHODS A total of 214 consecutive patients who underwent cardiac surgery with CPB were included in this study. TBV was retrospectively estimated using the following formulae: (1) Conventional TBV = actual BW × fixed 70 ml/kg, (2) gender-based modified TBV = ideal BW × 75 ml/kg (male) or 65 ml/kg (female) and (3) age-based modified TBV = ideal BW × 70 ml/kg (<65 years old) or 60 ml/kg (≥65 years old). The relationship between actual and predicted haemodilution rates calculated by these formulas was examined. RESULTS The actual haemodilution rate based on the haematocrit value was 24.4 ± 4.4%. There was no significant correlation between the actual and predicted haemodilution rates obtained by the conventional formula, whereas both modified formulae with the ideal BW showed a significant correlation. Furthermore, the age-based modified formula showed the highest correlation level (r = 0.45, P < 0.001) as well as a strong correlation between the actual and predicted postdilution haematocrit values (y = 0.903x + 3.385, R2 = 0.892). CONCLUSIONS The conventional formula is unable to predict the actual haemodilution rate accurately. Our new formula with a combination of the ideal BW and adjustment for age was shown to be useful for the accurate prediction of the haemodilution rate during CPB. Blood volume determination , Cardiopulmonary bypass , Haemodilution , Ideal body weight , Total blood volume INTRODUCTION In cardiac surgery, severe haemodilution during cardiopulmonary bypass (CPB) is thought to increase the risk of various complications, such as acute kidney injury and tissue hypoxia [1–4]. Ranucci et al. [5] previously found that the nadir haematocrit (HCT) value during CPB has a close relationship with perioperative acute kidney injury. Furthermore, Duque-Sosa et al. reported that the area under the curve for perioperative haemoglobin was an independent predictor of acute kidney injury [6]. These results suggest the importance of the prediction of the postdilution HCT value during CPB for the prevention of such complications. Maximum haemodilution generally occurs at the time of CPB initiation, when the clear solution for priming is directly added to the systemic blood circulation. In some cases, a portion of the clear priming volume must be replaced by allogeneic packed red blood cells in order to prevent an excessive drop in the HCT. Therefore, the accurate prediction of the haemodilution rate is important in order to obtain an appropriate postdilution HCT, which helps avoid preventable anaemia or the unnecessary transfusion of packed red blood cells. The haemodilution rate is mainly dependent on total blood volume (TBV), as the dilution volume (clear priming solution volume) is set for each CPB circuit. In general, TBV is simply and quickly calculated by multiplying the actual body weight (BW) with the blood volume (BV) per kilogram of body weight (BV/kg). Typically, 70 ml/kg is used as an index of the BV/kg [6, 7]. However, empirical errors are sometimes observed, and the status of patients can also vary. Obesity is an influencing factor, and previous studies have recommended that TBV be calculated according to the ideal body weight (IBW) [8, 9]. In addition, we speculate that IBW is influenced by differences in the body composition related to sex and age because the percentage of body fat is greater in females than in males and increases with age [10–12]. The aim of this study was to examine the efficacy of our novel formula using IBW with adjustments for gender and age to estimate TBV for a more accurate prediction of the haemodilution rate during CPB. MATERIALS AND METHODS Study population This retrospective case–control study was approved by our institutional ethics committee, with the need for individual patient consent waived. Between July 2013 and June 2015, 214 consecutive patients underwent cardiac surgery at a single hospital specializing in cardiovascular treatment. At our institution, central cannulation is performed for each case. Emergency cases and patients who required dialysis were excluded from this study. Cardiopulmonary bypass priming The CPB circuit and a hollow fibre membrane oxygenator (RX-25; TERUMO, Tokyo, Japan) were primed with a mixture of acetic acid Ringer’s solution, 300 ml of mannitol, and 4 KIU of heparin. When the BW was >70 kg, an arterial half-inch inner-diameter tubing roller pump and venous half-inch inner-diameter tube were primed with a total volume of 1100 ml. When the BW was <40 kg, 3/8-inch arterial and 3/8-inch venous tubes were selected and primed with a total volume of 900 ml. Otherwise, 3/8-inch arterial and half-inch venous tubes were selected and primed with a total volume of 1000 ml. Therefore, the total priming volume was determined by the size of the CPB circuit and ranged from 900 to 1100 ml. Blood transfusion was not used for CPB priming. Body mass index Body mass index (BMI) was defined as the BW in kilograms (kg) divided by the height (m) squared. Preobese or overweight was defined as BMI ≥25 in accordance with the World Health Organization classification. Calculation of the haemodilution rate and total blood volume The actual haemodilution rate was calculated from the HCT value measured with arterial blood gas samples (RAPIDLAB; SIEMENS, Munich, FRG) before and 10 min after CPB initiation (Formula 1). A sample obtained before CPB initiation was measured 3 min after a bolus dose of heparin. The predicted haemodilution rate and TBV were calculated using the conventional method (Formulae 2 and 3), as follows:   Actual dilution rate %=predilution HCT % − postdilution HCT(%) predilution HCT (%)  (1)  Predicted dilution rate %=priming volume mlpriming volume ml+TBV ml  (2)  TBV ml=BW kg×BVkg mlkg (3) For the conventional method, the actual BW and a fixed value of 70 ml/kg were used for the BW and BV/kg, respectively, to calculate TBV. For the modified methods, IBW was used instead of the actual BW (Supplementary Material, File S1) [13]. Calculation formula for IBW:   IBW kg=H2×22, where H = height (m) In addition, for the modified methods, the BV/kg was adjusted for gender and/or age. The following values were used for adjusting gender: males, 75 ml/kg; females, 65 ml/kg, as reported by Hilberath et al. [14]. The following values were used for adjusting the BV/kg by age: <65 years old, 70 ml/kg; ≥65 years old, 60 ml/kg, as reported by Davy and Seals [15]. Using the values obtained with these different approaches, the actual and predicted haemodilution rates were calculated, and their correlations were compared. Statistical analyses Continuous data are presented as mean ± standard deviation. The estimated TBV and haemodilution rate were analysed among the methods using a Mann–Whitney U-test. The correlation between the actual and predicted haemodilution rates was assessed using Spearman’s correlation coefficient. The most appropriate pairing was sought to predict the haemodilution rate at CPB initiation. All statistical analyses were performed using the JMP software program for Mac, ver. 10.11.6 (SAS Institute Inc., Cary, NC, USA). A P-value <0.05 was considered to be significant. RESULTS Patient characteristics Baseline patient characteristics and actual haemoglobin values are shown in Table 1. The average patient age was 70 ± 12 years (range 29–91 years), and 83 (39%) were female. The study population included 46 obese (BMI ≥25) and 168 non-obese (BMI <25) patients. Preoperative comorbidities, such as hypertension, diabetes mellitus, hyperlipidaemia and chronic obstructive pulmonary disease, and the types of procedures are shown in Table 1. Table 1: Patient characteristics Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  SD: standard deviation. Table 1: Patient characteristics Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  SD: standard deviation. Influence of body mass index on the haemodilution rate Using the conventional formula based on the actual BW and fixed BV/kg (70 ml/kg), the estimated TBV was 5064 ±867 ml in the 46 obese patients and 3779 ± 600 ml in the 148 non-obese patients, indicating a significant difference (P < 0.001). The predicted haemodilution rate for the obese patients was significantly lower than for the non-obese patients (17.0 ± 1.7% vs 20.6 ± 2.2%, P < 0.001), while the actual haemodilution rate was similar between them (23.4 ± 3.8% vs 24.7 ± 4.5%, P = 0.09). As shown in Fig. 1, the predicted haemodilution rate had a significant negative correlation with BMI, whereas the actual haemodilution rate did not. As a consequence, the discrepancy between the actual and predicted haemodilution rate was larger in the obese group than in the non-obese group (6.4 ± 3.2% vs 4.0 ± 4.7%, P < 0.001). Figure 1: View largeDownload slide The influence of body mass index on the actual and predicted haemodilution rates. BMI: body mass index. Figure 1: View largeDownload slide The influence of body mass index on the actual and predicted haemodilution rates. BMI: body mass index. Estimated total blood volume and haemodilution rate among different formulae with the actual and ideal body weight The actual HCT at anaesthesia induction, before CPB initiation and after CPB initiation was 39.2 ± 4.9%, 35.3 ± 4.7% and 26.8 ± 4.2%, respectively. TBV and the haemodilution rate calculated with the different approaches are shown in Table 2. The estimated TBV calculated by the conventional formula using the actual BW and fixed BV/kg (70 ml/kg) was 4067 ± 850 ml, although the range was quite wide (2275–7588 ml). When using IBW, the estimated TBV became significantly smaller at 3882 ± 472 ml with a narrower range (2765–4989 ml) (P < 0.001). Table 2: Estimated TBV and haemodilution rate Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    BW: body weight; CPB: cardiopulmonary bypass; HCT: haematocrit; SD: standard deviation; TBV: total blood volume. Table 2: Estimated TBV and haemodilution rate Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    BW: body weight; CPB: cardiopulmonary bypass; HCT: haematocrit; SD: standard deviation; TBV: total blood volume. Next, the estimated TBV calculated with the formula using IBW was further adjusted by gender and age. When adjusted by gender, TBV was calculated as 3967 ± 690 ml (2568–5346 ml), which was not significantly different from that obtained with the conventional method (P = 0.08). In contrast, the estimated TBV adjusted by age was 3496 ± 586 ml (2370–4990 ml), which was significantly lower than that obtained with the conventional method (P < 0.001). As a consequence, the haemodilution rate with that formula was significantly higher than that obtained with the conventional method (22.2 ± 2.3% vs 19.8 ± 2.7%, P < 0.001). Correlation between the actual and predicted dilution rates among different approaches The actual dilution rate was 24.4 ± 4.4%. There was no significant correlation between the actual and predicted haemodilution rates when using the conventional formula with the actual BW and fixed BV/kg (70 ml/kg) (Fig. 2A). However, there was a significant correlation between the actual and predicted haemodilution rates when using IBW (r = 0.39, P < 0.001) (Fig. 2B). The correlation between the actual and predicted haemodilution rates was most sensitive when using IBW and adjustment of BV/kg for age (r = 0.45, P < 0.001) compared to the adjustment of BV/kg for gender (r = 0.39, P < 0.001) (Fig. 3A and B). This formula showed a significantly high correlation compared to the conventional formula (P = 0.011). In addition, the predicted HCT [pre-dilution HCT × (1 − predicted haemodilution rate with the combination of IBW and adjustment for age)] showed the highest correlation with the actual HCT value after the initiation of CPB (y = 0.903x + 3.385, R2 = 0.892) (Fig. 4). Figure 2: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches using the total body weight (A) and ideal body weight (B). The blood volume per kilogram was fixed at 70 ml/kg. Figure 2: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches using the total body weight (A) and ideal body weight (B). The blood volume per kilogram was fixed at 70 ml/kg. Figure 3: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches adjusted for gender (A) and age (B). The ideal body weight was used in both groups. Figure 3: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches adjusted for gender (A) and age (B). The ideal body weight was used in both groups. Figure 4: View largeDownload slide The correlation between the measured and predicted haematocrit values using the ideal body weight and adjustment for age. Figure 4: View largeDownload slide The correlation between the measured and predicted haematocrit values using the ideal body weight and adjustment for age. DISCUSSION Three main findings were obtained in this study: (i) the conventional formula based on the actual BW and fixed BV/kg (70 ml/kg) was not able to accurately predict the haemodilution rate, especially in obese patients (BMI ≥25). TBV tended to be overestimated; thus the haemodilution rate was underestimated in those patients, and those errors tended to increase with increasing BMI. (ii) There was no significant correlation between the actual and predicted haemodilution rates obtained with the conventional formula. However, modification of the formula using IBW and adjustment for gender or age improved the predictive accuracy. (iii) The age-based modified formula using IBW was the most sensitive method for predicting the haemodilution rate and showed a strong correlation with the actual postdilution HCT value. The number of obese patients requiring cardiac surgery has been increasing over the past several decades. In a study by Marie et al. [7], some errors regarding the estimated haemodilution rate were observed in obese patients. In addition, Blessing et al. [16] reported that an appropriately sized CPB circuit should be selected based on the degree of obesity in a patient. The present study showed similar results, indicating that predicting the haemodilution rate is not simple with obese patients. In this study, we focused on the difference between the actual BW and IBW for the estimation of TBV. IBW excludes the effects of adipose tissue and skeletal muscle and is generally lower than the actual BW. Although fat and skeletal muscle mass differ among individuals, TBV based on the actual BW tends to be overestimated because of the influences of those tissues. In fact, we found that the haemodilution rate based on the actual BW did not correlate with measured variables, whereas that based on IBW was significantly closer to the actual values of our subjects. To account for variations in the body composition that occur depending on gender and age, which also influence the estimation of TBV, we further modified the formula by including those factors. Generally, the percentage of fat is greater in females than in males, while males tend to have greater muscle mass [17, 18]. The specific weights of fat and muscle are 0.9007 and 1.1000 g/m3, respectively, so the difference is slight [19]. Although the body fat percentage is clearly different between genders, the effect of muscle mass is not clear. To account for the influences of fat and muscle mass on TBV, the adjustment for gender may not be sufficient. However, the present results showed that age was indeed an influencing factor, as including it in the formula helped improve the accuracy of predicting TBV and haemodilution rate. We found that the predicted HCT value with the combination of IBW and adjustment for age strongly correlated with the actual postdilution HCT value and produced a very sensitive R2 value (0.892). TBV decreases with age due to decreased vessel elasticity caused by arteriosclerosis and the loss of overall water content. The effect of age seems to be stronger on TBV than that of gender. The accurate estimation of TBV is essential for determining the correct haemodilution rate, and this novel method may help reduce the need for blood transfusion in cardiovascular surgery with CPB. Limitations This study has several limitations. First, it was not performed as a prospective randomized analysis, and so there may be selection bias. Furthermore, the choice of the surgical procedure could not be decided randomly or prospectively. Different HCT levels, including extremal values and disease states, did not influence the results, but heart failure may influence the HCT level and haemodilution rate [7]. In this cohort, emergent and urgent operations were excluded, and so heart failure was largely controlled. However, certain effects, including the patient race, could not be fully adjusted for as only one race (East Asian) was included in this cohort. We estimated the haemodilution rate in 29 emergent cases, which is noteworthy, and none of the formulae, including the combination of IBW and age adjustment, showed a significant correlation. Therefore, further investigation is required for the accurate estimation of the haemodilution rate in uncontrolled heart failure and emergent cases. Second, the sample size was too small to provide statistical power, we have no data on children, and the formula for IBW cannot be generally used for children. Therefore, we think that the modified formula should not be adapted for children. Finally, the total priming volume was determined based on the size of the CPB circuit and ranged from 900 to 1100 ml. Differences in the priming volume may have influenced the results. CONCLUSION In conclusion, we found that the conventional method was unable to predict the actual haemodilution rate accurately with IBW proving more useful for estimating the BV and haemodilution rate during CPB. In addition, the combination of IBW and adjustment for gender and age resulted in increased sensitivity. We concluded that the combination of IBW and age adjustment is best for the prediction of the postdilution HCT value. SUPPLEMENTARY MATERIAL Supplementary material is available at ICVTS online. Conflict of interest: none declared. 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Novel method for estimating the total blood volume: the importance of adjustment using the ideal body weight and age for the accurate prediction of haemodilution during cardiopulmonary bypass

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Oxford University Press
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© The Author(s) 2018. 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/ivy173
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Abstract

Abstract OBJECTIVES Although total blood volume (TBV) is central to the estimation of the haemodilution rate during cardiopulmonary bypass (CPB), conventional formulas lack sufficient accuracy. The aim of this study was to establish a new formula using ideal body weight (BW) with adjustment for gender or age to estimate TBV for a more accurate prediction of the haemodilution rate during CPB. METHODS A total of 214 consecutive patients who underwent cardiac surgery with CPB were included in this study. TBV was retrospectively estimated using the following formulae: (1) Conventional TBV = actual BW × fixed 70 ml/kg, (2) gender-based modified TBV = ideal BW × 75 ml/kg (male) or 65 ml/kg (female) and (3) age-based modified TBV = ideal BW × 70 ml/kg (<65 years old) or 60 ml/kg (≥65 years old). The relationship between actual and predicted haemodilution rates calculated by these formulas was examined. RESULTS The actual haemodilution rate based on the haematocrit value was 24.4 ± 4.4%. There was no significant correlation between the actual and predicted haemodilution rates obtained by the conventional formula, whereas both modified formulae with the ideal BW showed a significant correlation. Furthermore, the age-based modified formula showed the highest correlation level (r = 0.45, P < 0.001) as well as a strong correlation between the actual and predicted postdilution haematocrit values (y = 0.903x + 3.385, R2 = 0.892). CONCLUSIONS The conventional formula is unable to predict the actual haemodilution rate accurately. Our new formula with a combination of the ideal BW and adjustment for age was shown to be useful for the accurate prediction of the haemodilution rate during CPB. Blood volume determination , Cardiopulmonary bypass , Haemodilution , Ideal body weight , Total blood volume INTRODUCTION In cardiac surgery, severe haemodilution during cardiopulmonary bypass (CPB) is thought to increase the risk of various complications, such as acute kidney injury and tissue hypoxia [1–4]. Ranucci et al. [5] previously found that the nadir haematocrit (HCT) value during CPB has a close relationship with perioperative acute kidney injury. Furthermore, Duque-Sosa et al. reported that the area under the curve for perioperative haemoglobin was an independent predictor of acute kidney injury [6]. These results suggest the importance of the prediction of the postdilution HCT value during CPB for the prevention of such complications. Maximum haemodilution generally occurs at the time of CPB initiation, when the clear solution for priming is directly added to the systemic blood circulation. In some cases, a portion of the clear priming volume must be replaced by allogeneic packed red blood cells in order to prevent an excessive drop in the HCT. Therefore, the accurate prediction of the haemodilution rate is important in order to obtain an appropriate postdilution HCT, which helps avoid preventable anaemia or the unnecessary transfusion of packed red blood cells. The haemodilution rate is mainly dependent on total blood volume (TBV), as the dilution volume (clear priming solution volume) is set for each CPB circuit. In general, TBV is simply and quickly calculated by multiplying the actual body weight (BW) with the blood volume (BV) per kilogram of body weight (BV/kg). Typically, 70 ml/kg is used as an index of the BV/kg [6, 7]. However, empirical errors are sometimes observed, and the status of patients can also vary. Obesity is an influencing factor, and previous studies have recommended that TBV be calculated according to the ideal body weight (IBW) [8, 9]. In addition, we speculate that IBW is influenced by differences in the body composition related to sex and age because the percentage of body fat is greater in females than in males and increases with age [10–12]. The aim of this study was to examine the efficacy of our novel formula using IBW with adjustments for gender and age to estimate TBV for a more accurate prediction of the haemodilution rate during CPB. MATERIALS AND METHODS Study population This retrospective case–control study was approved by our institutional ethics committee, with the need for individual patient consent waived. Between July 2013 and June 2015, 214 consecutive patients underwent cardiac surgery at a single hospital specializing in cardiovascular treatment. At our institution, central cannulation is performed for each case. Emergency cases and patients who required dialysis were excluded from this study. Cardiopulmonary bypass priming The CPB circuit and a hollow fibre membrane oxygenator (RX-25; TERUMO, Tokyo, Japan) were primed with a mixture of acetic acid Ringer’s solution, 300 ml of mannitol, and 4 KIU of heparin. When the BW was >70 kg, an arterial half-inch inner-diameter tubing roller pump and venous half-inch inner-diameter tube were primed with a total volume of 1100 ml. When the BW was <40 kg, 3/8-inch arterial and 3/8-inch venous tubes were selected and primed with a total volume of 900 ml. Otherwise, 3/8-inch arterial and half-inch venous tubes were selected and primed with a total volume of 1000 ml. Therefore, the total priming volume was determined by the size of the CPB circuit and ranged from 900 to 1100 ml. Blood transfusion was not used for CPB priming. Body mass index Body mass index (BMI) was defined as the BW in kilograms (kg) divided by the height (m) squared. Preobese or overweight was defined as BMI ≥25 in accordance with the World Health Organization classification. Calculation of the haemodilution rate and total blood volume The actual haemodilution rate was calculated from the HCT value measured with arterial blood gas samples (RAPIDLAB; SIEMENS, Munich, FRG) before and 10 min after CPB initiation (Formula 1). A sample obtained before CPB initiation was measured 3 min after a bolus dose of heparin. The predicted haemodilution rate and TBV were calculated using the conventional method (Formulae 2 and 3), as follows:   Actual dilution rate %=predilution HCT % − postdilution HCT(%) predilution HCT (%)  (1)  Predicted dilution rate %=priming volume mlpriming volume ml+TBV ml  (2)  TBV ml=BW kg×BVkg mlkg (3) For the conventional method, the actual BW and a fixed value of 70 ml/kg were used for the BW and BV/kg, respectively, to calculate TBV. For the modified methods, IBW was used instead of the actual BW (Supplementary Material, File S1) [13]. Calculation formula for IBW:   IBW kg=H2×22, where H = height (m) In addition, for the modified methods, the BV/kg was adjusted for gender and/or age. The following values were used for adjusting gender: males, 75 ml/kg; females, 65 ml/kg, as reported by Hilberath et al. [14]. The following values were used for adjusting the BV/kg by age: <65 years old, 70 ml/kg; ≥65 years old, 60 ml/kg, as reported by Davy and Seals [15]. Using the values obtained with these different approaches, the actual and predicted haemodilution rates were calculated, and their correlations were compared. Statistical analyses Continuous data are presented as mean ± standard deviation. The estimated TBV and haemodilution rate were analysed among the methods using a Mann–Whitney U-test. The correlation between the actual and predicted haemodilution rates was assessed using Spearman’s correlation coefficient. The most appropriate pairing was sought to predict the haemodilution rate at CPB initiation. All statistical analyses were performed using the JMP software program for Mac, ver. 10.11.6 (SAS Institute Inc., Cary, NC, USA). A P-value <0.05 was considered to be significant. RESULTS Patient characteristics Baseline patient characteristics and actual haemoglobin values are shown in Table 1. The average patient age was 70 ± 12 years (range 29–91 years), and 83 (39%) were female. The study population included 46 obese (BMI ≥25) and 168 non-obese (BMI <25) patients. Preoperative comorbidities, such as hypertension, diabetes mellitus, hyperlipidaemia and chronic obstructive pulmonary disease, and the types of procedures are shown in Table 1. Table 1: Patient characteristics Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  SD: standard deviation. Table 1: Patient characteristics Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  Variables  (n = 214)  Patient age (years), mean ± SD  70 ± 12  Female, n (%)  83 (39%)  Height (cm), mean ± SD  158.5 ± 10.0  Total body weight (kg), mean ± SD  58.1 ± 12.1  Ideal body weight (kg), mean ± SD  55.5 ± 6.7  Body surface area (m2), mean ± SD  1.584 ± 0.192  Body mass index (kg/m2), mean ± SD  23.01 ± 3.64  Hypertension, n (%)  144 (67)  Hyperlipidaemia, n (%)  96 (45)  Diabetes mellitus, n (%)  61 (29)  Chronic obstructive pulmonary disease, n (%)  40 (19)  Procedures, n (%)   Aortic valve replacement  59 (28)   Mitral valve replacement or repair  55 (26)   Double valve replacement  24 (11)   Coronary artery bypass grafting  22 (10)   Valve surgery with coronary bypass  52 (24)   Others  3 (1)  SD: standard deviation. Influence of body mass index on the haemodilution rate Using the conventional formula based on the actual BW and fixed BV/kg (70 ml/kg), the estimated TBV was 5064 ±867 ml in the 46 obese patients and 3779 ± 600 ml in the 148 non-obese patients, indicating a significant difference (P < 0.001). The predicted haemodilution rate for the obese patients was significantly lower than for the non-obese patients (17.0 ± 1.7% vs 20.6 ± 2.2%, P < 0.001), while the actual haemodilution rate was similar between them (23.4 ± 3.8% vs 24.7 ± 4.5%, P = 0.09). As shown in Fig. 1, the predicted haemodilution rate had a significant negative correlation with BMI, whereas the actual haemodilution rate did not. As a consequence, the discrepancy between the actual and predicted haemodilution rate was larger in the obese group than in the non-obese group (6.4 ± 3.2% vs 4.0 ± 4.7%, P < 0.001). Figure 1: View largeDownload slide The influence of body mass index on the actual and predicted haemodilution rates. BMI: body mass index. Figure 1: View largeDownload slide The influence of body mass index on the actual and predicted haemodilution rates. BMI: body mass index. Estimated total blood volume and haemodilution rate among different formulae with the actual and ideal body weight The actual HCT at anaesthesia induction, before CPB initiation and after CPB initiation was 39.2 ± 4.9%, 35.3 ± 4.7% and 26.8 ± 4.2%, respectively. TBV and the haemodilution rate calculated with the different approaches are shown in Table 2. The estimated TBV calculated by the conventional formula using the actual BW and fixed BV/kg (70 ml/kg) was 4067 ± 850 ml, although the range was quite wide (2275–7588 ml). When using IBW, the estimated TBV became significantly smaller at 3882 ± 472 ml with a narrower range (2765–4989 ml) (P < 0.001). Table 2: Estimated TBV and haemodilution rate Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    BW: body weight; CPB: cardiopulmonary bypass; HCT: haematocrit; SD: standard deviation; TBV: total blood volume. Table 2: Estimated TBV and haemodilution rate Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    Variables  Mean ± SD  Range (min–max)  P-value  Estimated TBV (ml)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  4067 ± 850  2275–7588     Ideal BW and fixed BW/kg (70 ml/kg)  3882 ± 472  2765–4989     Ideal BW and gender adjusted BW/kg  3967 ± 690  2567–5346     Ideal BW and age adjusted BW/kg  3496 ± 586  2370–4990    Predicted haemodilution rate (%)      <0.001   Actual BW and fixed BW/kg (70 ml/kg)  19.8 ± 2.6  12.7–28.3     Ideal BW and fixed BW/kg (70 ml/kg)  20.3 ± 1.6  16.9–25.1     Ideal BW and gender adjusted BW/kg  20.1 ± 2.3  16.0–26.0     Ideal BW and age adjusted BW/kg  22.2 ± 2.3  16.9–28.1    BW: body weight; CPB: cardiopulmonary bypass; HCT: haematocrit; SD: standard deviation; TBV: total blood volume. Next, the estimated TBV calculated with the formula using IBW was further adjusted by gender and age. When adjusted by gender, TBV was calculated as 3967 ± 690 ml (2568–5346 ml), which was not significantly different from that obtained with the conventional method (P = 0.08). In contrast, the estimated TBV adjusted by age was 3496 ± 586 ml (2370–4990 ml), which was significantly lower than that obtained with the conventional method (P < 0.001). As a consequence, the haemodilution rate with that formula was significantly higher than that obtained with the conventional method (22.2 ± 2.3% vs 19.8 ± 2.7%, P < 0.001). Correlation between the actual and predicted dilution rates among different approaches The actual dilution rate was 24.4 ± 4.4%. There was no significant correlation between the actual and predicted haemodilution rates when using the conventional formula with the actual BW and fixed BV/kg (70 ml/kg) (Fig. 2A). However, there was a significant correlation between the actual and predicted haemodilution rates when using IBW (r = 0.39, P < 0.001) (Fig. 2B). The correlation between the actual and predicted haemodilution rates was most sensitive when using IBW and adjustment of BV/kg for age (r = 0.45, P < 0.001) compared to the adjustment of BV/kg for gender (r = 0.39, P < 0.001) (Fig. 3A and B). This formula showed a significantly high correlation compared to the conventional formula (P = 0.011). In addition, the predicted HCT [pre-dilution HCT × (1 − predicted haemodilution rate with the combination of IBW and adjustment for age)] showed the highest correlation with the actual HCT value after the initiation of CPB (y = 0.903x + 3.385, R2 = 0.892) (Fig. 4). Figure 2: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches using the total body weight (A) and ideal body weight (B). The blood volume per kilogram was fixed at 70 ml/kg. Figure 2: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches using the total body weight (A) and ideal body weight (B). The blood volume per kilogram was fixed at 70 ml/kg. Figure 3: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches adjusted for gender (A) and age (B). The ideal body weight was used in both groups. Figure 3: View largeDownload slide The relationship between the predicted and actual haemodilution rates noted in the different approaches adjusted for gender (A) and age (B). The ideal body weight was used in both groups. Figure 4: View largeDownload slide The correlation between the measured and predicted haematocrit values using the ideal body weight and adjustment for age. Figure 4: View largeDownload slide The correlation between the measured and predicted haematocrit values using the ideal body weight and adjustment for age. DISCUSSION Three main findings were obtained in this study: (i) the conventional formula based on the actual BW and fixed BV/kg (70 ml/kg) was not able to accurately predict the haemodilution rate, especially in obese patients (BMI ≥25). TBV tended to be overestimated; thus the haemodilution rate was underestimated in those patients, and those errors tended to increase with increasing BMI. (ii) There was no significant correlation between the actual and predicted haemodilution rates obtained with the conventional formula. However, modification of the formula using IBW and adjustment for gender or age improved the predictive accuracy. (iii) The age-based modified formula using IBW was the most sensitive method for predicting the haemodilution rate and showed a strong correlation with the actual postdilution HCT value. The number of obese patients requiring cardiac surgery has been increasing over the past several decades. In a study by Marie et al. [7], some errors regarding the estimated haemodilution rate were observed in obese patients. In addition, Blessing et al. [16] reported that an appropriately sized CPB circuit should be selected based on the degree of obesity in a patient. The present study showed similar results, indicating that predicting the haemodilution rate is not simple with obese patients. In this study, we focused on the difference between the actual BW and IBW for the estimation of TBV. IBW excludes the effects of adipose tissue and skeletal muscle and is generally lower than the actual BW. Although fat and skeletal muscle mass differ among individuals, TBV based on the actual BW tends to be overestimated because of the influences of those tissues. In fact, we found that the haemodilution rate based on the actual BW did not correlate with measured variables, whereas that based on IBW was significantly closer to the actual values of our subjects. To account for variations in the body composition that occur depending on gender and age, which also influence the estimation of TBV, we further modified the formula by including those factors. Generally, the percentage of fat is greater in females than in males, while males tend to have greater muscle mass [17, 18]. The specific weights of fat and muscle are 0.9007 and 1.1000 g/m3, respectively, so the difference is slight [19]. Although the body fat percentage is clearly different between genders, the effect of muscle mass is not clear. To account for the influences of fat and muscle mass on TBV, the adjustment for gender may not be sufficient. However, the present results showed that age was indeed an influencing factor, as including it in the formula helped improve the accuracy of predicting TBV and haemodilution rate. We found that the predicted HCT value with the combination of IBW and adjustment for age strongly correlated with the actual postdilution HCT value and produced a very sensitive R2 value (0.892). TBV decreases with age due to decreased vessel elasticity caused by arteriosclerosis and the loss of overall water content. The effect of age seems to be stronger on TBV than that of gender. The accurate estimation of TBV is essential for determining the correct haemodilution rate, and this novel method may help reduce the need for blood transfusion in cardiovascular surgery with CPB. Limitations This study has several limitations. First, it was not performed as a prospective randomized analysis, and so there may be selection bias. Furthermore, the choice of the surgical procedure could not be decided randomly or prospectively. Different HCT levels, including extremal values and disease states, did not influence the results, but heart failure may influence the HCT level and haemodilution rate [7]. In this cohort, emergent and urgent operations were excluded, and so heart failure was largely controlled. However, certain effects, including the patient race, could not be fully adjusted for as only one race (East Asian) was included in this cohort. We estimated the haemodilution rate in 29 emergent cases, which is noteworthy, and none of the formulae, including the combination of IBW and age adjustment, showed a significant correlation. Therefore, further investigation is required for the accurate estimation of the haemodilution rate in uncontrolled heart failure and emergent cases. Second, the sample size was too small to provide statistical power, we have no data on children, and the formula for IBW cannot be generally used for children. Therefore, we think that the modified formula should not be adapted for children. Finally, the total priming volume was determined based on the size of the CPB circuit and ranged from 900 to 1100 ml. Differences in the priming volume may have influenced the results. CONCLUSION In conclusion, we found that the conventional method was unable to predict the actual haemodilution rate accurately with IBW proving more useful for estimating the BV and haemodilution rate during CPB. In addition, the combination of IBW and adjustment for gender and age resulted in increased sensitivity. We concluded that the combination of IBW and age adjustment is best for the prediction of the postdilution HCT value. SUPPLEMENTARY MATERIAL Supplementary material is available at ICVTS online. Conflict of interest: none declared. 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Journal

Interactive CardioVascular and Thoracic SurgeryOxford University Press

Published: Jun 4, 2018

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