Irrationality of Allogeneic Red Blood Cell Transfusion in Intraoperative Cell Salvage Patients: a Retrospective Analysis

Manjiao Ma, Xuerong Yu＊, Yi Wang, Yuguang Huang,Sufang Lu, Yuan Tian, Bing Bai

Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China

Key words: intraoperative cell salvage; rational transfusion; patient blood management;preoperative anemia

ALLOGENEIC transfusion has been regarded to be associated with increased risks of hemolytic and allergic reactions, acute lung injury, infectious diseases, and immunomodulation.1In addition to these transfusion-associated diseases, the shortage of allogeneic blood has posed an increasingly important issue in China. Therefore, intraoperative cell salvage (ICS) has been widely used to mitigate the demand for allogeneic blood transfusion and its related complications.

However, many patients who use ICS still receive allogeneic blood transfusion in their clinical management. A systematic review on perioperative allogeneic blood transfusion reported that ICS did not reduce the demand of allogeneic red blood cell (RBC)transfusion and its intraoperative transfusion rate was 38.3%±0.17% in over half (53.7%，36/67) of the randomized controlled trials analyzed.2The reasons may lie in the individual factors of patients, including preoperative anemia,3,4children or the elderly,5serious comorbidities or high risk score of anesthesia according to the American Society of Anesthesiologists (ASA),disease severity (such as long-segment spinal diseases),5and operative factors (such as significant blood loss, long surgical duration,3,5-7excessive postoperative drainage).3Additionally, physician’s personal preference of the trigger level of HGB for transfusion also plays an important role in clinical patients care. For instance, it was reported that some surgeons or anesthesiologists rejected the relatively low trigger level of HGB for transfusion,8and were not likely to change their decision-making habits.9

A large prospective randomized trial, Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair（FOCUS）study, confirmed that compared with the restrictive strategy for transfusion(symptomatic anemia or the triggering HGB level of 80 g/L), the liberal strategy for blood transfusion (the triggering HGB level of 100 g/L) did not minimize the patients’ mortality, the inability to walk independently on 60-day follow-up, and the in-hospital morbidity in the elderly patients with cardiovascular disease risks.10Therefore, doctors are supposed to transfuse allogeneic blood to patients with HGB＜100g/L according to the Technical Specifications of Clinical Blood Transfusion of China, and had better to adopt the strict transfusion strategy, which is to transfuse only when HGB level is under 70 g/L.

This retrospective study investigated the rate of allogeneic RBC transfusion in ICS patients, aiming at evaluating reasonableness of allogeneic RBC transfusion and identifying the risk factors for the irrationality of allogeneic RBC transfusion, for the purpose to provide clues to improve the patient blood management(PBM).

MATERIALS AND METHODS

Patients selection and data collection

This retrospective study was approved by the institutional ethic committee and the informed consent from the patients were waived. We reviewed the medical records of inpatients who were associated with ICS approach in Peking Union Medical College Hospital from January 2013 to July 2014. The patients were from the departments of orthopedics, neurosurgery, vascular surgery, obstetrics and gynecology, hepatic surgery,general surgery, urology, thoracic surgery, stomatology, otorhinolaryngology, and cardiac surgery. Cases were excluded because of incomplete medical records,or cardiopulmonary bypass cardiac surgeries in which blood loss and salvaged blood volume cannot be evaluated accurately due to the washing of bypass blood by cell saver. The clinical medical records we collected included patient age, gender, body weight, preoperative hemoglobin (HGB), intraoperative estimated blood loss, salvaged blood volume, intraoperative allogeneic RBC transfusion or not, and the volume of transfusion.

Transfusion performance and decision making

All patients received autotransfusion with Haemonetics Cell Saver 5+ system (Haemonetics Corporation,Braintree, MA, USA) throughout surgeries. Clinically,the decision whether patients receive allogeneic RBC transfusion after reinfusion of salvaged blood was made by consensus of discussion between the anesthesiologist and the surgeon based on their personal judgments. For example, some physicians made decision of transfusion when the estimated blood loss was greater than 500 mL.

Variable estimations

The theoretical HGB level at the end of the operation was estimated by the following formula:

HGBpost-operative（g/L）=[HGBpre-operative(g)?HGBintra-op-erativebloodloss(g)+HGBsalvagedblood(g)] / estimated blood volume (EBV, L).

The variables in above formula were estimated as followed:

Patients grouping and data management

According to whether the enrolled patients received allogeneic RBC transfusion in the medical records, we divided them into non-transfusion group and transfusion group, and compared the clinical characteristics between the two groups. Based on the theoretical HGB, all the patients was assigned into two groups: group A, patients with theoretical HGB＜100 g/L，group B, patients with theoretical HGB≥100 g/L. For patients in group B, the clinical variables were compared between who received allogeneic RBC transfusion and who did not.Specifically, variables of patient age, ratio of blood loss/EBV and preoperative HGB were analyzed as both continuous and categorical variables in order to thoroughly check the clinical significance: ①age: stratified into children (＜14 years), adults (14≤age＜65 years) and the elderly (≥65 years); ②ratio of blood loss to EBV:low(＜20%), medium(20%-50%) and massive bleeding(＞50%); ③preoperative HGB level: anemia(HGB＜120 g/L in male and HGB＜110 g/L in female) and non-anemia according to the diagnostic criteria of China.

Statistical analysis

Statistical analysis was conducted by SPSS 18.0 software. Continuous variables were described as means and standard deviations if normally distributed, or as medians if abnormally distributed. Clinical characteristics of different groups were compared by independent t test for normally distributed continuous variables, or independent Mann-Whitney U test for non-parametric test. Logistic regression was performed to identify risk factors for irrationality of allogeneic RBC transfusion.The differences were considered statistically significant if P value was less than 0.05.

RESULTS

Demographic and clinical data

Of 1631 patients who were associated with ICS approach in the medical records, 144 cases were excluded according to exclusion criteria, and 1487 patients were enrolled in this study. There were 467 (31.4%)patients who received intraoperative transfusion, and the mean allogeneic RBC was 736.19±534.11mL.Comparing to those who did not, patients with transfusions were significantly younger with lower body weight, lower preoperative HGB, significant higher ratio of blood loss to EBV, and higher salvaged blood volume (Table 1). There was no significant difference in the surgical departments and gender between the two groups of patients.

Rates of allogeneic RBC transfusion in patients with different theoretical HGB levels

Of 1487 patients in this study, there were 174 (11.7%)cases whose theoretical HGB＜100 g/L (group A) and 1313 (88.3%) cases whose theoretical HGB≥100 g/L(group B). Of 174 cases in the group A, 126(72.4%)cases received transfusion and 48(27.6%) cases did not. Of 1313 cases in the group B, 341(26.0%) cases received transfusion, the mean transfusion volume was 611.7±400.4 ml, and 972(74.0%) cases did not receive transfusion. The difference of transfusion rates between two groups was found to be significant(χ2=153.8, P＜0.001).

Table 1. Demographic and clinical characteristics of enrolled patients (n=1487)§

Differences in clinical characteristics between non-transfusion patients and transfusion patients in group B

Compared to patients who did not receive transfusion in group B, those who received transfusion were younger, with lower body weight and slightly lower preoperative HGB, but had significantly larger salvaged blood volume and higher ratio of blood loss to EBV when analyzed in terms of continuous variables (Table 2). When compared in terms of categorical variable,preoperative anemia, which is based on preoperative HGB, was not significantly different between the patients who received transfusion and those did not(U=?1.396, P=0.163). The age and ratio of blood loss to EBV were significantly different between the two subgroups (both P＜0.001). The surgical departments where patients received therapy were not different significantly between the transfusion and non-transfusion patients (P＞0.05).

Risk factor analysis of irrational allogeneic RBC transfusion in group B

For patients with theoretical HGB≥100 g/L, among variables that was significantly different between patients received transfusion and those did not，the logistic regression analysis showed that preoperative HGB (continuous variable, OR=1.975, 95% CI: 1.23-3.8, P=0.005) and ratio of blood loss/EBV (category variable, OR=5.392, 95% CI:3.57-8.14, P＜0.001)were the independent risk factors for irrationality of allogeneic RBC transfusion (Table 3). The body weight(OR=0.989, 95% CI：0.979-1.000, P=0.048) and the salvaged blood volume (OR=1.002, 95% CI:1.001-1003, P＜0.001) were also statistically significant, but their OR values approximated 1, indicating their small clinical significances.

DISCUSSION

It has been reported that the risk of allogeneic RBC transfusion can be reduced by 38%(RR 0.61,95% CI 0.55～0.77) with 204mL volume reduction of allogeneic RBC transfusion by using ICS.2The efficacy of ICS in some orthopedics or cardiac surgeries was getting more definite. ICS can reduce patients’ risks of blood-borne infection, postoperative infection, tumor recurrence and immune modulation, and relieve blood shortages.12

In this observational study, the intraoperative allogeneic RBC transfusion rate was 31.4%(467 out of1487), which was comparable to 38.3% and 39.4% as reported in the literatures.2,13It was reported that in some regions of China, the rate of intraoperative irrational allogeneic blood transfusion was approximately 58.7%,14and the rate of irrational allogeneic RBC transfusion ranged from 33.6% to 49.2%.15,16In USA and Australia, the reported rate of surgical related irrational allogeneic RBC transfusion reached up to 63.3%,and in 70% of these patients, the HGB values were between 80 g/L and 99 g/L.17The irrational allogeneic RBC transfusion may also exist in patients of ICS. Dr.Wong et al reported that the autologous transfusion at the mean (standard deviation) hemoglobin level of 92.6 (8.7) g/L and above was irrational transfusion.They also assessed the adherence of doctors to blood transfusion guideline and found that 20.3% of patients whose HGB between 71g/L and 100 g/L received RBC transfusion just because of their anemic symptoms;nevertheless, only 2.2%(4/180) patients whose HGB levels was greater than 100 g/L received allogeneic RBC transfusion.18When doctors strictly followed the blood transfusion protocol, the relative risk of allogeneic RBC transfusion in ICS patients was reduced by 48%.13

Table 2. Comparison of clinical variables between subgroups of non-transfusion and transfusion patients in group B (n=1313)§

Table 3. Logistic regression analysis of risk factors for irrational allogeneic RBC transfusion in group B (n=1313)

In the institution where this study was conducted,the point-of-care HGB test is not routinely done before and after blood transfusion, and the transfusion decisions are usually made based on the experience of anesthesiologists or surgeons. Therefore, this study evaluated the irrationality of allogeneic RBC transfusion by calculating the theoretical HGB level instead of actual HGB value. Another reason is that the actual HGB level is of little value in evaluating the rationality of allogeneic RBC transfusion when both autologous and allogeneic RBC was transfused. Our results showed that the patients whose theoretical HGB was ＞100 g/L accounted for 88.3% (1313/1487) of all cases in this study.Among them, 341 patients received transfusion, yielding an irrational RBC transfusion rate of 26.0%, though according to the Technical Specifications of Clinical Blood Transfusion of China, these patients should not have received blood transfusion.

Furthermore, we found that the preoperative HGB and ratio of blood loss to EBV were independent risk factors for irrational allogeneic RBC transfusion in ICS patients, particularly, the ratio of blood loss to EBV greater than 50% could approximately quintuple the risk for irrational RBC transfusion in patients with ratio of blood loss to EBV under 20%. Although logistic regression analysis also found the body weight and the salvaged blood volume were statistically risk factors,the ORs of both factors approximated 1, indicating clinically they may have small influence on the irrational RBC transfusion in ICS patients.

Patients’ preoperative HGB level was highly related to the rate of allogeneic RBC transfusion in this study. It has been reported that in patients with preoperative HGB ＞ 160 g/L, 141～160 g/L, 121～140 g/L,101～120 g/L and 81～100 g/L, the rates of allogeneic RBC transfusion were 8.3%, 7.8%, 28.2%, 60.2% and 85.7% respectively (P＜0.0001).18The incidence of preoperative anemia in patients receiving non-cardiac surgeries (except for colorectal surgery) was 34%,and preoperative anemia significantly correlated to the increased requirements of perioperative allogeneic blood, increased risks of postoperative infections, mortality, complications and prolonged hospitalization.19However, in this study, regardless of transfusion or not,the mean pre-operative HGB level of group B did not meet the diagnostic criteria of anemia, and the pre-operative anemia rate in non-transfusion patients was comparable to that of transfusion patients (P=0.163).These data suggested that physicians were apt to take a liberal transfusion strategy in practice for patients with low preoperative HGB level, disregarding whether the preoperative HGB level had reached the suggested trigger level for transfusion, or whether the degree of anemia would really affect the outcomes of patients.

Some studies have also concluded that massive blood loss was an independent risk factor in perioperative allogeneic RBC transfusion in ICS patients.6,20However, it is interesting that salvaged blood volume was not a major factor influencing the decision of allogeneic RBC transfusion in our study. Additionally, by calculation, we observed that the theoretical HGB level remained above 100 g/L after re-infusing washed salvaged cell in most cases. So most of the ICS patients might not need allogeneic RBC. Thus, we presumed that the surgeons or anesthesiologists did not consider ICS to be able to reduce the intraoperative demand of allogeneic RBC, and still chose allogeneic blood transfusion if patients experienced heavy blood loss.

The main limitation of our study is that the actual HGB values were not examined before and after blood transfusion in clinical practice of our hospital, so we had to use theoretical HGB level instead. Besides, this study was conducted in a single medical center, and multi-centric study is needed for further investigation.

To conclude, irrationality of allogeneic RBC transfusion in ICS patients may be associated with the patient body weight, salvaged blood volume, preoperative HGB and ratio of blood loss to EBV, especially the latter two.Determining the HGB levels should be done before transfusion to avoid unnecessary blood administration.Doctors’ knowledge in blood management should be updated, and the awareness of rational transfusion need to be improved for better patients’ care.

REFERENCES

1. Miller RD, Eriksson LI, Fleisher L. Miller’s Anesthesia.8th Edition. Philadelphia: Churchill Livingstone; 2010.p.1851-8.

2. Carless PA, Henry DA, Moxey AJ, et al. Cell salvage for minimising perioperative allogeneic blood transfusion.Cochrane Database Syst Rev 2010(4): CD001888.doi: 10.1002/14651858. CD001888.pub4.

3. Liang J, Shen J, Chua S, et al. Does intraoperative cell salvage system effectively decrease the need for allogeneic transfusions in scoliotic patients undergoing posterior spinal fusion? A prospective randomized study. Eur Spine J 2015; 24(2): 270-5. doi:10.1007/s00586-014-3282-2.

4. C?té CL, Yip AM, MacLeod JB, et al. Efficacy of intraoperative cell salvage in decreasing perioperative blood transfusion rates in first-time cardiac surgery patients: a retrospective study. Can J Surg 2016;59(5): 330-6. doi: 10.1503/cjs.002216.

5. Kelly PD, Parker SL, Mendenhall SK, et al. Cost-effectiveness of cell saver in short-segment lumbar laminectomy and fusion (≤3 levels). Spine 2015; 40(17):E978-85. doi: 10.1097/BRS.0000000000000955.

6. Owens RK 2nd, Crawford CH 3rd, Djurasovic M, et al. Predictive factors for the use of autologous cell saver transfusion in lumbar spinal surgery. Spine 2013; 38(4): E217-22. doi: 10.1097/BRS.0b013e-31827f044e.

7. Canan CE, Myers JA, Owens RK, et al. Blood salvage produces higher total blood product costs in single-level lumbar spine surgery. Spine 2013; 38(8):703-8. doi: 10.1097/BRS.0b013e3182767c8c.

8. Yazer MH, Waters JH. How do I implement a hospital-based blood management program? Transfusion 2012; 52(8): 1640-5. doi: 10.1111/j.1537-2995.2011.03451.x.

9. Beaty CA, Haggerty KA, Moser MG, et al. Disclosure of physician-specific behavior improves blood utilization protocol adherence in cardiac surgery. Ann Thorac Surg 2013; 96(6): 2168-74. doi: 10.1016/j.athoracsur.2013.06.080.

10. Carson JL, Terrin ML, Noveck H, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011;365(26):2453-62. doi:10.1056/NEJMoa1012452.

11. Lewis SM, Brain BJ, Bates I. Basic haematological techniques. In: Practical Haematology. 9th Edition.Philadelphia: Churchill Livingstone; 2001. p.19-46.

12. Sikorski RA, Rizkalla NA, Yang WW, et al. Autologous blood salvage in the era of patient blood management. Vox sanguinis 2017; 112(6): 499-510. doi:10.1111/vox.12527.

13. Carless P, Moxey A, O’Connell D, et al. Autologous transfusion techniques: a systematic review of their efficacy. Transfus Med 2004; 14(2): 123-44. doi: 10.1111/j.0958-7578.2004.0489.x.

14. Zhang B, Jiang JM. The systemic review on the appraisal research of the rationality of blood transfusion in some districts. Chin J Hosp Admin 2011; 27(8): 622-6. doi: 10.3760/cma.j.issn.1000-6672.2011.08.019.

15. Sun DH. Scientific and rational analysis of clinical blood use in 3460 cases. Modern Prac Med 2010;22(4): 405-9. Chinese. doi: 10.3969/j.issn.1671-0800.2010.04.026.

16. Yang BC, Kong LK, Shao CP, et al. Review of 2597 cases of blood transfusion and evaluation of the appropriateness. Chin J Blood Transfus 2008; 21(03): 193-6.Chinese. doi: 10.3969/j.issn.1004-549X.2008.03.012.

17. Shander A, Fink A, Javidroozi M, et al. Appropriateness of allogeneic red blood cell transfusion: the international consensus conference on transfusion outcomes. Transfus Med Rev 2011; 25(3): 232-46 e53.doi: 10.1016/j.tmrv.2011.02.001.

18. Wong S, Tang H, de Steiger R. Blood management in total hip replacement: an analysis of factors associated with allogenic blood transfusion. ANZ J Surg 2015;85(6): 461-5. doi: 10.1111/ans.13048.

19. Shander A, Van Aken H, Colomina MJ, et al. Patient blood management in Europe. Br J Anaesth 2012;109(1): 55-68. doi:10.1093/bja/aes139.

20. Gause PR, Siska PA, Westrick ER, et al. Efficacy of intraoperative cell saver in decreasing postoperative blood transfusions in instrumented posterior lumbar fusion patients. Spine 2008; 33(5): 571-5. doi:10.1097/BRS.0b013e3181657cc1.