Risk factors for allogeneic red blood cell transfusion in adult spinal deformity surgery
Article information
Abstract
Study Design
Retrospective study.
Purpose
To investigate the risk factors for allogeneic red blood cell (RBC) transfusion in adult spinal deformity (ASD) surgery.
Overview of Literature
Studies have not thoroughly explored the roles of intraoperative hypothermia, autologous blood donation, and hemostatic agent administration, which would provide a better understanding of the risk for perioperative RBC transfusion in ASD surgery.
Methods
The medical records of 151 patients with ASD who underwent correction surgery between 2012 and 2021 were retrospectively reviewed. Estimated blood loss and perioperative allogeneic transfusion were examined. Patients were categorized into two groups based on whether they received perioperative allogeneic blood transfusion. Logistic regression analysis was employed to investigate the effect of age, sex, blood type, body mass index, American Society of Anesthesiologists’ physical status, preoperative hemoglobin level, autologous blood donation, global spine alignment parameters, preoperative use of anticoagulants or antiplatelet medicine and nonsteroidal anti-inflammatory drugs, number of instrumented fusion levels, total operative duration, three-column osteotomy, lateral interbody fusion, pelvic fixation, intraoperative hypothermia, use of gelatin-thrombin based hemostatic agents, and intraoperative tranexamic acid (TXA) with simultaneous exposure by two attending surgeons.
Results
The estimated blood loss was 994.2±754.5 mL, and 71 patients (47.0%) received allogeneic blood transfusion. In the logistic regression analysis, the absence of intraoperative TXA use and simultaneous exposure (odds ratio [OR], 26.3; 95% confidence interval [CI], 7.6–90.9; p<0.001), lack of autologous blood donation (OR, 21.2; 95% CI, 4.4–100.0; p<0.001), and prolonged operative duration (OR, 1.6; 95% CI, 1.3–1.9; p<0.001) were significant independent factors for perioperative allogeneic blood transfusion in ASD surgery.
Conclusions
Autologous blood storage, intraoperative TXA administration, and simultaneous exposure should be considered to minimize perioperative allogeneic blood transfusion in ASD surgery, particularly in patients with anticipated lengthy surgeries.
Introduction
Correction surgery for adult spinal deformity (ASD) is usually associated with considerable blood loss because of extensive soft tissue dissection, osteotomies, and prolonged surgical time [1]. Massive bleeding frequently necessitates allogeneic red blood cell (RBC) transfusion. Perioperative allogeneic transfusions are associated with the risk of postoperative complications, such as infections, cardiovascular complications, and prolonged hospital stay [2–4]. Therefore, predicting the risk of blood loss and the need for RBC transfusion in ASD surgery is important to reduce the likelihood of postoperative complications.
To minimize blood loss, autologous blood donation, antifibrinolytic agents, hemostatic agents, hypotensive anesthesia, and hypothermia prevention are commonly employed [5]. Patient demographic, surgical, and anesthetic factors have been explored to provide a better understanding of the risk for perioperative RBC transfusion in ASD surgery. However, the roles of intraoperative hypothermia, autologous blood donation, and hemostatic agent administration have not been thoroughly explored [6–8]. Therefore, this study aimed to comprehensively investigate the risk factors for perioperative allogeneic RBC transfusion in ASD correction surgery.
Materials and Methods
Patient population
The medical records of 153 patients with ASD who underwent correction surgery at Seirei Sakura Citizen Hospita between January 2012 and October 2021 were reviewed retrospectively. The study included patients who underwent thoracolumbosacral fusion at ≥4 levels [6] and excluded two patients who underwent this procedure at <4 levels. Ultimately, 151 cases were included.
The institutional review board of Seirei Sakura Citizen Hospital approved the study protocol, including the review of patient records (no., 2020007). The study was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. All patients provided informed consent for their data to be included in studies submitted for publication.
Autologous blood collections
Autologous blood was collected between 35 and 6 days preoperatively. Specifically, 400 mL of autologous blood was collected weekly, and 400–1,600 mL of autologous blood was collected as requested by the surgeon. However, autologous donation was avoided in patients with anemia (hemoglobin [Hb] <10 g/dL) or suspected bacteremia.
Surgical procedure
Deformity correction was performed in all patients using transforaminal lumbar interbody fusion, lateral lumbar interbody fusion (LLIF), or grade 1–5 osteotomy with cancellous allografts and autografts [9–12]. Then, the conventional open approach in posterior surgery was routinely selected for the release of facet joints and bone grafts. The number of fusion levels and correction techniques are determined at the discretion of the attending surgeons. Two-staged surgery is selected in cases requiring anter-posterior combined surgery or grade ≥3 osteotomies [13]. Tranexamic acid (TXA) is routinely administered intraoperatively (loading dose of 1,000 mg, followed by continuous infusion of 10 mg/kg/hr) [14–18], and surgeries are simultaneously performed by two attending surgeons in posterior surgery since May 2017 [1,19,20]. Bleeding episodes were controlled using conventional methods, such as cautery, manual compression, or suturing; microporous polysaccharide hemospheres, including Arista (Bard Davol Inc., Warwick, UK); and oxidized cellulose, such as Surgicel (Ethicon Inc., Raritan, NJ, USA). When these agents cannot control the bleeding, gelatin-thrombin-based hemostatic agents, such as Floseal (Baxter Healthcare Corp., Deerfield, IL, USA) or Surgiflo (Ethicon Inc.), have been used since October 2014. The cell-saver system is used in posterior surgery, and all surgeries were performed by the same team of four experienced spine surgeons.
Anesthetic procedure
All patients underwent general anesthesia by a single anesthesiologist and received forced-air warming blankets (Bair Hugger System; 3M, St. Paul, MN, USA). Controlled hypotension was maintained by the intravenous administration of nicardipine with a target decrease in mean blood pressure of 90±10 mm Hg. The cell-saver system was used in all cases, and the need for intraoperative transfusion was determined according to the surgical criterion of Hb level <8 g/dL. Preoperative autologous or cell-saver blood was selected first. Subsequently, allogeneic RBCs, platelets, or fresh-frozen plasma was transfused.
Postoperative course
All patients received similar postoperative management. A drainage tube was used at the surgical site postoperatively, which was removed 2 days postoperatively. Postoperative transfusion was performed when the Hb level was <7 g/dL. Patients were occasionally transfused when their Hb level was 7–8 g/dL, and bleeding continued from the drainage tube with or without mean arterial pressure of <90 mm Hg and/or urine output <0.5 mL/kg/hr.
Patient data
Baseline data, including age at surgery, sex, blood type, body mass index (defined as weight/height squared [kg/m2]), American Society of Anesthesiologists’ (ASA) physical status [21], and preoperative Hb level (g/dL) immediately before surgery at admission, were retrospectively investigated. The preoperative use of anticoagulants or antiplatelets and nonsteroidal anti-inflammatory drugs (NSAIDs), number of patients who received allogeneic RBC transfusion, and amount of autologous blood donation were also investigated. Surgical factors, such as instrumented fusion levels, total operative duration, and need for grade ≥3 osteotomies, LLIF, and pelvic fixation were collected. Hypothermia was defined as a decrease in the core temperature <36°C at least once during surgery [22]. The use of TXA and simultaneous exposure and gelatin-thrombin-based hemostatic agents was also investigated. Preoperative and postoperative (1 week postoperatively) global spine alignment parameters, including the sagittal vertical axis (SVA), pelvic incidence (PI), thoracic kyphosis, lumbar lordosis (LL), and PI–LL, were assessed on lateral whole-spine radiographs [23]. Intraoperative and postoperative estimated blood losses (EBLs) from the drainage tube at the surgical site from immediately to 2 days postoperatively were investigated. The % estimated blood volume (%EBV) was calculated using the following formula: EBL/weight (mL/kg). Perioperative (intraoperatively to 2 days operatively) use and amount of allogeneic RBC transfusion were investigated.
Statistical analyses
Continuous and categorical variables were analyzed using Student t-test and Fisher’s exact test, respectively. Patients were categorized into the transfusion and non-transfusion groups according to the use of allogeneic RBC transfusion. Baseline characteristics, surgical factors, and global spine alignment parameters were compared between the two groups. Spearman’s rank-order correlation was conducted to assess collinearity. Factors with a correlation coefficient of ≥0.5 were excluded in the multivariate analysis. A stepwise multivariate logistic regression analysis was conducted to identify predictors of the need for allogeneic RBC transfusion. Odds ratios (ORs) are reported with 95% confidence intervals (CIs). A p-value <0.05 was considered significant in the tests of statistical inference. Furthermore, a post hoc power analysis was reported, and all analyses were performed using IBM SPSS Statistics for Windows ver. 25.0 (IBM Corp., Armonk, NY, USA).
Results
Patient characteristics
Intraoperative and postoperative EBLs were 994.2±754.5 mL (range, 25–3,810 mL) and 801.3±491.6 mL (range, 0–2,610 mL), respectively. Seventy-one patients (47.0%) received perioperative allogeneic RBC transfusions. The mean amount of allogeneic RBC transfused in these patients was 1,763.4±1,042.7 mL. Age was significantly higher (p=0.024), the number of patients and units of preoperative autologous blood transfused were significantly lower (p<0.001), and preoperative Hb level was significantly lower (p=0.025) in the transfusion group than in the non-transfusion group (Table 1).
Comparison of patient characteristics between the groups with and without perioperative allogeneic RBC transfusion
Global spine alignment and surgical factors
The preoperative PI–LL was significantly higher (p=0.021) and grade ≥3 osteotomies (p<0.001) was significantly more common in the transfusion group than in the non-transfusion group (Table 2). Conversely, the use of TXA and simultaneous exposure were significantly less common (p<0.001), total operative duration was significantly longer (p<0.001), and intraoperative and postoperative EBLs (p<0.001) were significantly greater in the transfusion group than in the non-transfusion group (Table 3).
Comparison of global spine alignment parameters between the groups with and without perioperative allogeneic RBC transfusion
Comparison of surgical factors between the groups with and without perioperative allogeneic RBC transfusion
Risk factors
Spearman’s rank-order correlation revealed collinearity factors, including LLIF and grade ≥3 osteotomies (r=0.53, p<0.001). EBL demonstrated collinearity with fusion levels, use of TXA and simultaneous exposure, and surgical time (r=0.41, −0.51, and 0.55; p<0.001). The ASA physical status showed collinearity with the preoperative use of anticoagulants or antiplatelets (r=0.46, p<0.001). PI–LL also correlated with other global spine parameters, including the SVA, PI, and LL (r=0.72, 0.61, and 0.84; p<0.001). Therefore, LLIF, EBL, preoperative use of anticoagulants or antiplatelets, SVA, PI, and LL were excluded from the multivariate analysis. In the stepwise multivariate logistic regression analyses with 16 potential predictors (age, sex, body mass index, ASA physical status, blood type, hypothermia, preoperative autologous blood donation, preoperative Hb, preoperative use of NSAIDs, preoperative PI–LL, grade ≥3 osteotomies, pelvic fixation, fusion levels, TXA and simultaneous exposure use, gelatin-thrombin-based hemostatic agent use, and total operative duration), the absence of TXA and simultaneous exposure use (OR, 26.3; 95% CI, 7.6–90.9; p<0.001), absence of autologous blood donation (OR, 21.2; 95% CI, 4.4–100.0; p<0.001), and longer operative duration (OR, 1.6; 95% CI, 1.3–1.9; p<0.001) were independent risk factors for allogeneic RBC transfusion (Table 4).
Logistic regression analysis of risk factors for perioperative allogeneic red blood cell transfusion
A post hoc power analysis showed that this study had the power to detect differences (autologous donated blood, 0.998; use of TXA and simultaneous exposure, 1; and total operative duration, 1). In the periodical comparison of intraoperative EBLs and number of patients with allogeneic RBC transfusion, the intraoperative EBL ranged from 741 to 1,472 mL. The proportion of patients receiving allogeneic RBC transfusion ranged from 39% to 79% before the use of TXA and simultaneous exposure from 2012 to 2017; however, the intraoperative EBL ranged from 475 to 866 mL. Conversely, the proportion of patients with allogeneic RBC transfusion ranged from 9% to 17% after TXA and simultaneous exposure between 2018 and 2021 (Fig. 1).
Periodical comparisons of intraoperative estimated blood loss (EBL) and proportion of patients with allogeneic red blood cell (RBC) transfusion.
Transfusion-associated adverse events
Four and two patients in the transfusion and non-transfusion groups experienced wound infections, respectively (p=0.707). Cardiovascular events including deep venous thrombosis (n=2), pulmonary embolism (n=1), stroke (n=1), and ischemic colitis (n=1) occurred in five patients in the RBC transfusion group, and pulmonary embolism (n=1) and acute celiac artery compression syndrome (n=1) developed in two patients in the non-transfusion group [24] (p=0.254). The incidence of wound infection and cardiovascular events was not different between the RBC transfusion and non-transfusion groups.
Discussion
The results of this study showed that the absence of TXA use and simultaneous exposure, absence of autologous blood donation, and longer operative duration were independent risk factors of allogeneic RBC transfusion. To the best of our knowledge, this is the first report to examine the role of global spine alignment, blood type, hypothermia, and use of autologous blood donation and gelatin-thrombin-based hemostatic agents in determining the need for RBC transfusion after ASD surgery. Additionally, the implementation of TXA administration, simultaneous exposure, and autologous blood donation and has reduced the intraoperative EBL to <1,000 mL and the proportion of allogeneic RBC transfusion to <20% since 2018.
Age ≥65 years, female sex, ASA physical status class >2, prolonged operative duration, three-column osteotomy, pelvic fixation, and long fusion were reported previously as risk factors and the use of antifibrinolytic agents, including TXA, as a protective factor for perioperative allogeneic RBC transfusion in ASD surgery [6–8]. A study also reported the effectiveness of autologous blood donation in reducing allogeneic RBC transfusions [25]. Furthermore, our study findings regarding the effect of prolonged operative duration, intraoperative TXA administration, and autologous blood donation were consistent with those of previous reports.
Particularly, in this study, the ORs for the absence of TXA use and simultaneous exposure were as high as 30, highlighting the synergistic effect of these methods. Previously, intraoperative TXA administration has been reported to reduce intraoperative EBLs and the need for allogeneic RBC transfusion in ASD correction surgery [14–18]. Additionally, simultaneous surgery performed by two attending senior surgeons also decreased EBLs in surgery for ASD or adolescent idiopathic scoliosis [1,19,20]. Autologous blood donation was found to be a protective factor against allogeneic RBC transfusion, which is consistent with the findings of other studies [25]. Therefore, whenever possible, autologous blood donation should be implemented unless there are insurance restrictions or contraindications. A longer operative duration was also identified as a risk factor for allogeneic RBC transfusion because surgeries involving long fusion, three-column osteotomies, and interbody fusion tend to require longer operative time [26]. If a lengthy procedure is anticipated, autologous blood transfusion should be considered if feasible.
Age >65 years, female sex, ASA physical status class >2, and preoperative Hb level of <11.5 g/dL have been reported as risk factors for allogeneic RBC transfusion in ASD surgery [6–8]. In this study, age and preoperative Hb level were significant factors in the univariate analysis but not independent risk factors in the multivariate analysis. The effect of autologous blood donation masked that of preoperative Hb level because anemia is a contraindication for autologous blood donation. Furthermore, in this study, the effects of age and sex were limited compared with the use of TXA, autologous blood donation, and operative duration. The number of patients with ASA physical status class >2 was also small (n=11); therefore, a significant difference could not be observed. In this study, a type O blood was not a risk factor for allogeneic RBC transfusion. Patients with type O blood have lower plasma levels of von Willebrand factor and factor VIII and bleed more than those with other blood types [27]; however, the association of blood loss with type O and non-type O blood remains controversial [28,29].
Regarding surgical factors, three-column osteotomy, long fusion, and pelvic fixation were identified as risk factors for allogeneic RBC transfusion [7,8]. In this study, a three-column osteotomy was a significant factor in the univariate analysis but not in the multivariate analysis. In contrast, according to the results of the logistic analysis, total operative duration was significantly associated with transfusion risk. The effect of total operative duration masked the effects of specific surgical procedures because these procedures typically require longer surgical duration [26]. In addition, intraoperative hypothermia is closely related to EBL [22]. In this study, the effect of hypothermia was mitigated by promptly raising the body temperature of the patient using forced-air warming blankets, even in cases with hypothermia.
Furthermore, the use of gelatin-thrombin-based hemostatic agents can reduce the risk of intraoperative blood loss during spine surgery [30]. However, these agents did not show a significant effect on intraoperative EBL because they were not used in patients with slight bleeding.
Moreover, no significant difference in the risk of complications was found between patients with and without allogeneic RBC transfusion. However, the rates of urinary tract infection, surgical site infection, and pneumonia were significantly higher in patients with allogeneic RBC transfusion than in those without such transfusion [6]. Therefore, allogeneic RBC transfusion should be minimized to reduce the risk of such complications.
This study had some limitations. First, the use of TXA and simultaneous exposure were initiated in May 2017, making it challenging to determine which intervention contributed more to the observed outcomes. Therefore, if the use of TXA and simultaneous exposure could be investigated separately, the OR for the use of TXA and simultaneous exposure and autologous blood donation could be different. Second, TXA use and simultaneous exposure were grouped by the date of initiation in May 2017 rather than through random allocation. Therefore, we cannot dismiss the possibility that the decrease in intraoperative EBL was influenced by the learning curve associated with ASD surgery. Third, postoperative EBL was not pure blood but included seroma. However, because hematocrit in drainage fluid was not measured, pure postoperative blood loss could not be investigated. Fourth, the prevalence of postoperative complications was not different between the two groups because of the small sample size. Therefore, further studies with larger sample sizes are warranted to demonstrate the negative effect of allogeneic RBC transfusion. Despite these limitations, the strength of this study is attributed to the detailed investigation of various potential risk factors for allogeneic RBC transfusion in ASD surgery, which may help minimize the risk of transfusion.
Conclusions
This study showed that the absence of TXA use and simultaneous exposure, autologous blood donation, and longer operative times were independent risk factors of allogeneic RBC transfusion in ASD surgery. Therefore, we recommend the use of TXA and simultaneous exposure and autologous blood donation whenever feasible, particularly in anticipated prolonged surgeries.
Notes
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Author Contributions
Conception and design: YI. Data acquisition: YI, TK, TS, TA, YO, MM, SM. Analysis of data: YI, TK. Drafting of the manuscript: YI, TK. Critical revision: all authors. Supervision: all authors. Final approval: all authors.