Older adults can be defined as those 65 and older (Centers for Disease Control and Prevention, 2013). In 2015, older adults accounted for 8.5% of the global population, and these numbers continue to grow (He, Goodkind, & Kowal, 2016). A common occurrence in older adults, anemia affects 10% of those living in the community and >50% of those residing in long-term care (Thein et al., 2009). Anemia has been shown to be associated with poor health outcomes, functional decline, reduced quality of life (Maraldi et al., 2006; Thein et al., 2009; Yang et al., 2011), and concurrent illnesses and comorbidities (Brunskill, Wilkinson, Doree, Trivella, & Stanworth, 2015).
Anemia is defined as a hemoglobin (Hb) level <12 g/dL in women and <13 g/dL in men (World Health Organization, 1968). Hb concentration is lower, on average, in older adults than in their younger counterparts, which can result in poor physical performance, such as muscle weakness and falls (Gregersen, 2016; Resnick, Sabol, Galik, & Gruber-Baldini, 2010). Often mild and asymptomatic in older adults if left untreated, anemia has been shown to increase disability, morbidity, and mortality (Maraldi et al., 2006; Thein et al., 2009). A special type of anemia—postoperative anemia—has been associated with delirium and reduced quality of life (Thein et al., 2009), as well as reduced physical performance.
Although packed red blood cell (PRBC) transfusions have been used to treat anemia and often provide life-saving treatment to critical patients, they have been shown to be associated with increased morbidity and mortality (O'Keeffe et al., 2010; Rubinstein et al., 2013; Shaw et al., 2013). Evidence exists to support an association between blood transfusion and clinical complications, such as electrolyte imbalances, organ failure, fluid overload, and predisposition to nosocomial infections, possibly due to cellular changes that occur during storage (Bennett-Guerrero et al., 2007; Wang, Sun, Solomon, Klein, & Natanson, 2012); these outcomes may be exacerbated in older adult patients with decreased physiologic reserve. To address these risks and decrease unnecessary transfusions, recent PRBC trans-fusion guidelines promote restrictive (i.e., a transfusion indicated with Hb level of 7 to 8 g/dL) versus liberal (i.e., a transfusion indicated with Hb level of 9 to 10 g/dL) transfusion strategies where possible (Carson et al., 2016). To contribute to the understanding of the risks and benefits of transfusions, the purpose of the current study was to perform a systematic review of the current literature regarding PRBC transfusion indications, practices, and associated outcomes in the older adult population.
Hb level often triggers the decision to complete a PRBC transfusion, with specific thresholds being established (Brunskill et al., 2015). Other reasons PRBC transfusions may be triggered are due to patient age and existing comorbidities (Brunskill et al., 2015). PRBC transfusion thresholds are often lower for older adults compared to their younger counterparts, despite a lack of clinical evidence to support this practice (Ad et al., 2015). This lack of evidence is a significant gap in the literature, as older adults experienced >1 million hospitalizations in 2012, with the number of stays where a PRBC transfusion was required doubling between 1997 and 2011 (Pfunter, Wier, & Stocks, 2013; Weiss & Elixhauser, 2014).
Compounding the issue, older adults are more at risk for PRBC transfusion–associated overload as they may have difficulty tolerating even moderate volumes of fluid due to comorbidities, such as cardiovascular disease (Ad et al., 2015; Brunskill et al., 2015). Despite these increased risks and being more vulnerable to poor outcomes, previous studies have often combined older adults with their younger counterparts or excluded them from studies altogether. For example, a recent systematic review by Lelubre and Vincent (2013) evaluated the effects of PRBC transfusion on outcomes in critically ill patients, but included studies of all adult patients (19 or older). As older adults present a complex scenario for patient care and may experience different outcomes compared to younger patient populations, evidence to support use of current PRBC transfusion guidelines among this population must be evaluated.
To evaluate the science surrounding PRBC transfusion among older adults, a comprehensive search in PubMed, CINAHL, and Embase was completed using the terms “blood transfusion” and “aged.” Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to guide and address the quality of this review (Moher, Liberati, Tetzlaff, & Altman, 2009). To include the most current state of the science as it applies to clinical practice, the search was filtered for randomized controlled trials (RCTs) published within the past 5 years (January 1, 2011 to April 4, 2016). After eliminating duplicates, a total of 535 abstracts were reviewed (Figure). To be included in this review, studies needed to involve participants 65 or older who were also undergoing procedures that involved either receiving or preventing PRBC transfusion, or evaluated outcomes associated with PRBC transfusions in any manner. Reference lists of relevant articles were also reviewed and one additional citation was accrued. The current authors reached consensus on all abstracts and reviewed full text for inclusion in the analysis. A total of 10 articles were found relevant to this review. Quality of studies was evaluated using the SQUIRE (Standards for Quality Improvement Reporting Excellence) guidelines (Ogrinc et al., 2015) (Table A, available in the online version of this article). Values were assigned for each item response, with a possible total ranging from 0 to 40; higher scores indicated higher bias.
Article selection process.
Bias Assessment Tool
Quality of Studies
All studies were conducted outside of the United States, in Europe (Gregersen, Borris, & Damsgaard, 2015a,b; Gregersen, Damsgaard, & Boris, 2015; Greiff et al., 2012; Kiessling et al., 2012; Serrano-Trenas et al., 2011; van Boven et al., 2013) and Asia (Fan et al., 2014; Okazaki et al., 2013; Yu et al., 2012). Four studies focused on cardiac surgery patients (Greiff et al., 2012; Kiessling et al., 2012; van Boven et al., 2013; Yu et al., 2012); five focused on orthopedic surgery patients, specifically for hip surgery (Fan et al., 2014; Gregersen, Boris, et al., 2015a,b; Gregersen, Damsgaard, et al., 2015; Serrano-Trenas et al., 2011); and one focused on gastrointestinal surgery (Okazaki et al., 2013). Due to the variety of interventions and outcomes evaluated, meta-analysis of the data was not conducted. Sample sizes ranged from 48 to 284 participants (mean = 128 participants), indicating modest but adequate samples across trials. Among the 10 studies evaluated, the average bias score was 13 (SD = 3.4, range = 8 to 19) of a possible 40 points, indicating overall low bias. The three greatest sources of bias among studies were the discussion of methods used to assess completeness and accuracy of data, details related to missing data, and discussion of costs and strategic trade-offs associated with the study.
A summary of the evidence examined is shown in Table B (available in the online version of this article).
Serrano-Trenas et al. (2011) evaluated the use of intravenous (IV) iron sucrose before hip fracture surgery in 200 patients. The investigators found that, compared to those in the control group, patients who received IV iron sucrose experienced a reduction in PRBC transfusion requirements (14% vs 46%, respectively; p = 0.004) and faster recovery of RBC indices. However, this finding only applied to patients with intracapsular fractures with an admission or baseline Hb level ≥12 g/dL. Thus, IV iron sucrose before hip fracture surgery for older adults with higher preoperative Hb levels may promote improved postoperative outcomes.
Grieff et al. (2012) examined the use of tranexamic acid in PRBC transfusion prevention among 64 older adults undergoing combined aortic valve replacement and coronary artery bypass graft (CABG) surgery. Tranexamic acid is one of the most commonly used drugs for hemostasis in cardiac surgery, and was delivered as an IV bolus prior to surgery in the intervention group. Although not significant, patients who received tranexamic acid experienced less blood loss compared with a saline placebo group (695 mL, interquartile range [IQR] = 470 to 1,590 mL vs 1,035 mL, IQR = 517 to 1,485 mL, p = 0.36). Patients who received tranexamic acid also received fewer PRBC units (3 units, IQR = 2 to 5 units vs 5 units, IQR = 3 to 7 units, p = 0.049). Although tranexamic acid did not significantly reduce postoperative bleeding, it reduced the need for PRBC transfusion.
Kiessling et al. (2012) performed a randomized trial to determine the safety and efficacy of pre-filling of the extracorporeal circuit with autologous blood to reduce blood product transfusion requirements in 72 older adults undergoing surgery requiring cardiopulmonary bypass. Compared with standard of care, investigators found no significant differences in transfusion of PRBC after pre-coating (control mean [SD] = 900  mL vs pre-coat mean [SD] = 730  mL), transfusion of platelets (control mean [SD] = 60  mL vs pre-coat mean [SD] = 40  mL), or transfusion of fresh frozen plasma (control mean [SD] = 150  mL vs pre-coat mean [SD] = 240  mL). Thus, pre-coating the circuit with autologous blood had no influence on postoperative transfusion requirements.
Yu et al. (2012) compared hemostasis with two methods: bone wax versus fibrin sealant in 40 older adults undergoing CABG via median sternotomy incision. Fibrin sealant (i.e., a compound comprising plasma protein and thrombin) is widely used for hemostasis in cardiac procedures worldwide, whereas bone wax (made of bees wax and petroleum jelly) is rarely used in Western medicine. Blood loss in the first 24 hours was reduced in the fibrin sealant group compared with the bone wax group (mean [SD] = 186.67 [49.53] mL vs mean [SD] = 333.75 [60.49] mL, respectively; p < 0.001), as was total blood loss (fibrin sealant: mean [SD] = 326.19 [67.24] mL vs bone wax: mean [SD] = 516 [8.46] mL; p < 0.001). In addition, those who received fibrin sealant required an average of 3.6 units (SD = 1.25 units) of PRBC compared with an average of 7.4 units (SD = 2.13 units) for those who received bone wax (p < 0.001). Investigators noted that although fibrin sealant lowered blood loss and reduced PRBC transfusion requirements compared to bone wax, bone wax is not commonly used due to “embolic and wound healing problems” (Yu et al., 2012, p. 644), thus limiting the generalizability of this work.
In their randomized trial, van Boven et al. (2013) examined the use of restrictive fluid management, similar to restrictive versus liberal transfusion, in 60 patients older than 70 undergoing CABG to determine its effectiveness in protecting organ function and improving postoperative outcomes. Participants were randomized into three groups: minimal fluid CABG (mCABG), off-pump CABG, and conventional CABG. mCABG is a technique that was developed to reduce hemodilution while offering a blood preservation effect. Among participants, 65% of the conventional CABG, 30% of the off-pump CABG, and 20% of the mCABG group required PRBC transfusion, with this group trending toward using less platelets and fresh frozen plasma products. The authors concluded that the fluid restriction during mCABG contributed to the maintenance of physiological balances perioperatively, as well as the improved ventilation times and decreased blood product consumption postoperatively.
Fan et al.'s (2014) trial evaluated development of postoperative delirium in 186 older adults undergoing elective unilateral hip replacement with use of spinal anesthesia. Participants were randomized to either a restrictive transfusion strategy (Hb < 8.0 g/dL) or a liberal transfusion strategy (Hb < 10.0 g/dL). Investigators evaluated patients using the Confusion Assessment Method for the intensive care unit and found no difference in development of delirium based on transfusion strategy (21.3% for the transfusion strategy group vs 23.9% for the liberal transfusion strategy group, p > 0.05). They concluded that a restrictive transfusion strategy was safe and effective among older adults undergoing hip replacement surgery, and did not increase the risk of postoperative delirium.
As part of the Transfusion Requirements in Frail Elderly (TRIFE) RCT, Gregersen, Borris, et al. (2015b) examined how PRBC transfusion strategies (restrictive vs liberal) impact physical recovery from disabilities and mortality. In the study, 284 frail adults 65 and older with hip fracture were assigned to the restrictive group (Hb <9.7 g/dL; <6 mmol/L) or liberal group (Hb <11.3 g/dL; <7 mmol/L) for PRBC transfusions within the first 30 days postoperatively. Investigators found no significant differences in measures of activities of daily living between groups. For those older adults residing in a nursing home, 30-day mortality was higher in the restrictive group (hazard ratio [HR] = 2.4, 95% confidence interval [CI] [1.1, 5.2]; p = 0.03), as was 90-day mortality (36% in restrictive group vs 20% in liberal group, HR = 2.0, 95% CI [1.1, 3.6]; p = 0.01).
Gregersen, Borris, et al. (2015a) conducted a second study from the TRIFE RCT examining the impact of restrictive versus liberal PRBC transfusion strategy on quality of life, depression, and activities of daily living for frail older adults with hip fracture. A total of 157 nursing home residents 65 and older with a Mini-Mental State Examination score ≥5 were assigned to either the restrictive group (Hb <9.7 g/dL; <6 mmol/L) or liberal group (Hb <11.3 g/dL; <7 mmol/L) for PRBC transfusions within the first 30 days postoperatively. Quality of life and depression scores were similar for both groups at 30-day and 1-year follow up. In the restrictive group, the median activities of daily living score, which was measured by the modified Barthel Index and ranged from 0 to 100 (100 = best), at 1-year post-surgery was 76 (IQR = 48 to 86), which represented a sum-score increase of 9.18 points from day 30 until 1 year post-surgery. For the liberal transfusion group, the median activities of daily living score was 78 (IQR = 61 to 86) at 1 year post-surgery, with the sum-score increasing by 16 points from day 30 to 1 year post-surgery. The difference in the liberal transfusion group was statistically greater than that in the restrictive group (95% CI [0.41, 13.3]; p = 0.03), indicating a better recovery of mobility and physical functioning for the liberal transfusion group.
Using data from the TRIFE RCT, Gregersen, Damsgaard, et al. (2015) compared the association between a liberal or restrictive PRBC transfusion strategy and risk of infection for frail older adults after unilateral hip surgery. The Comprehensive Geriatric Assessment Frailty Index was used to measure level of frailty and equality level of frailty between groups. Of 227 adults 65 and older, 72% of patients in the restrictive transfusion group developed an infection compared to 66% of those in the liberal group (risk ratio [RR] = 1.08; 95% CI [0.93, 1.27]; p = 0.29). Investigators concluded that a more liberal transfusion strategy was not associated with a higher risk of infection for this group of patients. Conversely, Okazaki et al. (2013) found in their RCT examining 48 older adults (age >70) undergoing gastroenterological surgery that the use of perioperative blood transfusion was an independent risk factor for infectious complications (odds ratio [OR] = 6.476, 95% CI [1.179, 35.58]; p = 0.032). In this study, perioperative blood transfusion was defined as including the transfusion of PRBCs preoperatively, intraoperatively, and up to 48 hours postoperatively. The difference in the findings of these two studies could be attributed to the difference in patient populations.
The current analysis revealed 10 investigations of methods to prevent PRBC transfusion or outcomes associated with PRBC transfusion in the older adult population. Among these, five studies (50%) focused on interventions to prevent blood loss or PRBC transfusion, and the remaining five focused on outcomes associated with PRBC transfusion. All studies focused on one of three surgical populations, including cardiac, orthopedic, and gastrointestinal.
Findings among PRBC transfusion prevention studies were mixed and may not represent methods commonly used in Western medicine. Although more research is required, promising techniques for PRBC transfusion prevention were highlighted. Administering IV iron sucrose, tranexamic acid, bone wax, and fluid restriction during surgery may help decrease the need for PRBC transfusion in older adults.
Findings were also inconclusive about outcomes following PRBC transfusion. Restrictive PRBC transfusion was found to be a safe and effective treatment in one study (Fan et al., 2014), but others found a more liberal PRBC transfusion strategy to be beneficial in promoting recovery and physical functioning postoperatively (Gregersen, Borris, et al., 2015a), and decreasing mortality (Gregersen, Borris, et al., 2015b).
Collectively, these findings indicate a wide range of interventions and outcomes evaluated, with little consistency in methodology and overall inconclusive results. The inconsistency could be a result of the limitation regarding the lack of distinction between the groups of older adults. For frail older adults, the benefits of a more liberal PRBC transfusion strategy could outweigh the risks. Older adults present a particularly challenging population for PRBC transfusion research due to several factors. Due to the aging process, older adults commonly experience multiple comorbidities and an extensive health history. These issues may result in a limited degree of physical resilience that can impact their need for transfusion and physiological reserve (Nakamura et al., 2015). Older adults are generally excluded from transfusion research due to the added complexity of their care. Exceptions to this exclusion can be found, such as the studies in the current review that included the areas of gastrointestinal, orthopedic, and cardiac surgery. To help address the heterogeneity of the older adult population, more research is needed to examine the unique needs of older adults as they continue to age, as well as the role of comorbidities and frailty on PRBC transfusion prevention and outcomes.
Another issue that could have contributed to the inconsistent findings in the current review is the length of storage time for the PRBCs. A primary source of concern with PRBC transfusion is the effect of the storage lesion, or stored PRBC toxicity, on patient outcomes. Per federal guidelines, PRBCs may be stored for a maximum of 42 days (American Association of Blood Banks, 2013). However, during this time, cells experience a change in their overall structure that results in an inability to transport oxygen once transfused, and potential breakdown of the cell membrane that allows release of intracellular contents (Orlov & Karkouti, 2015). These changes worsen with increased storage duration and may result in a stored PRBC toxicity in the transfused patient (Orlov & Karkouti, 2015). Thus, patients with decreased physiologic reserve, such as older adults with multiple comorbidities, may be more prone to the effects of the storage lesion when transfused.
Recent findings of an international, randomized trial (N = 20,858) revealed no difference in in-hospital mortality rate among adults 18 or older who received either the freshest or oldest PRBCs available (Heddle et al., 2016). However, investigators did not control for patient age in their analyses, collect data on patient comorbidities, or indicate the reason for PRBC transfusion other than a primary admitting diagnosis category (e.g., cardiovascular disease, cancer). The mechanisms by which stored PRBC toxicity impacts patient outcomes have yet to be fully elucidated, and the effect of stored PRBC age on patient outcomes remains controversial. PRBC age was not controlled for in the studies reviewed, and thus may provide additional insight regarding the findings. Studies examining the length of storage duration and its impact on the outcomes for older adults are needed to determine the maximum storage duration for safely transfusing this population.
Other factors that potentially influence PRBC transfusion requirements and outcomes include biases and physiological factors related to patient gender and ethnicity. In a post-hoc analysis of >6,500 patients who underwent CABG or orthopedic surgery (total hip or total knee replacement), investigators reported a significantly higher transfusion rate in women compared to men across all types of surgery (CABG: 81% vs 49%, total hip: 46% vs 24%, total knee: 37% vs 23%; p < 0.0001) despite similar median age (mean age for women = 70 years [IQR = 56 to 84 years], mean age for men = 67 years [IQR = 53 to 81 years]) (Gombotz, Schreier, Neubauer, Kastner, & Hofmann, 2016). Women also received transfusions of one or two PRBCs more often than men, although investigators noted that this might be the result of women more often experiencing higher levels of anemia rather than a bias in care delivery (Gombotz et al., 2016).
In a secondary analysis of a nation-wide sample, Qian et al. (2014) examined racial disparities in the use of perioperative blood transfusion among patients undergoing major surgery, including CABG (n = 25,849), total hip replacement (n = 42,933), and isolated colectomy (n = 8,255) in 87 hospitals. Median age of patients was similar across surgery types, ranging from 57 to 65 years. After controlling for patient age, gender, admission status, severity of illness, and comorbidities, Black patients were more likely than White patients to receive one or more units of PRBCs during CABG (OR = 1.41, 95% CI [1.13, 1.76], p = 0.002) and total hip replacement (OR = 1.39, 95% CI [1.20, 1.62], p < 0.001) (Qian et al., 2014). Thus, biases in care delivery and differences in physiological response to hemorrhage and PRBC transfusion should be considered in the older adult population.
Evidence indicates that anemia in older adults adversely affects their morbidity and mortality, which may be especially true when surgery is required (Vochteloo et al., 2011). When comparing liberal and restrictive transfusion therapies for patients 60 and older undergoing cardiac surgery, Nakamura et al. (2015) found that the cardiovascular risk posed by anemia was more harmful than the risks associated with PRBC transfusion. Risks from PRBC transfusion include increased infection rates, acute hemolytic and nonhemolytic reactions, and transfusion-associated circulatory overload (Nakamura et al., 2015; Vochteloo et al., 2011).
Despite these risks from PRBC transfusion, the risks from anemia (e.g., cardiogenic shock, increased intensive care unit and hospital stay) were greater for patients undergoing cardiac surgery (Nakamura et al., 2015). Adding to the evidence of risks of anemia, a retrospective study examining outcomes for 1,262 older adult patients with hip fracture who were treated surgically found that mortality rate, delirium incidence, and discharge rates to a nursing home were significantly worse for those experiencing anemia preoperatively (Vochteloo et al., 2011). The study also showed that postoperative anemia was an independent risk factor for worse outcomes for hip fracture patients (Vochteloo et al., 2011).
It could be argued that older adults undergoing preplanned surgeries or interventions may be more physiologically stable than older adults who have experienced a trauma and, as such, the findings from the current review may be limited and must be interpreted with caution. Inclusion of only those patients physiologically stable enough to endure major procedures introduces a source of bias and should be considered in the interpretation of the findings. In addition to the limited generalization, three of 10 studies originated from the same parent study, which could contribute to selection bias and put too much emphasis on the findings from those studies. Having a cutoff age of 65 or older may have eliminated studies that had applicable findings that would have contributed to the current conclusions.
Another limitation of this review was the lack of stratification of the age groups for those 65 and older. An individual who is 85 years old may face different risks and health concerns compared to one who is 65 years old. Due to the small sample of relevant articles, all individuals 65 and older were considered as one group. In future studies, it would be helpful to examine the potential differences facing older adults in different age groups to highlight potential distinctions so they may be factored into PRBC guidelines.
To assist with clinical decision making, more RCTs are needed that examine the clinical outcomes for older adults receiving PRBC transfusions, including mortality, infection rates, functional ability, and quality of life. More definitive conclusions are needed regarding the risks and benefits for this potentially vulnerable patient population. Future studies should examine the differences between older adults and their younger counterparts when receiving PRBCs. Another area that shows promise is restrictive PRBC transfusions. However, results have been mixed and it remains to be determined whether the benefits of restrictive transfusions outweigh the risks anemia poses for older adults.
One area of interest that continues to grow is the concept of patient blood management (PBM). PBM is defined by the Society for the Advancement of Blood Management (2017) as “the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss in an effort to improve patient outcome.” PBM bundles are available to promote implementation of these methods in the clinical setting, and include topics that range from PBM program development and inclusion of stake-holders to management of anemia and coagulopathy, and methods of benchmarking patient outcomes (Meybohm et al., 2017).
Implications for Clinical Practice
The older adult population continues to grow; thus, clinicians who care for them must be aware of the risks and benefits of current treatment practices. Blood transfusions are commonly used to treat anemia in older adults due to a variety of conditions and in multiple settings aside from the perioperative arena. Current blood transfusion guidelines set by the American Association of Blood Banks (2013) do not include indications for frail and/or older adult patients. Older adults regularly experience multiple comorbidities and decreased physiologic resilience, meaning they may require additional monitoring during and after PRBC transfusions to prevent complications. Advance practice providers should consider the traditional transfusion indications of lab values and vital signs in the older adult population, as well as the individual needs of the patient with regard to their tolerance of blood transfusion and its potential consequences. In addition, advanced practice nurses prescribing these treatments should carefully consider potential alternatives to transfusion, if possible. Such considerations may maximize patient outcomes and decrease use of health care resources or provide a more cost-effective method for treatment.
Evidence of the best practices for PRBC transfusions for the older adult surgical population remains inconclusive and contradictory. To optimize care for older adults, continued study of the indications and outcomes of PRBC transfusions and development of protocols to address their unique requirements are needed.
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- Qian, F., Eaton, M.P., Lustik, S.J., Hohmann, S.F., Diachun, C.B., Pasternak, R. & Glance, L.G. (2014). Racial disparities in the use of blood transfusion in major surgery. BMC Health Services Research, 14, 121. doi:10.1186/1472-6963-14-121 [CrossRef]
- Resnick, B., Sabol, V., Galik, E. & Gruber-Baldini, A.L. (2010). The impact of anemia on nursing home residents. Clinical Nursing Research, 19, 113–130. doi:10.1177/1054773810362089 [CrossRef]
- Rubinstein, C., Davenport, D.L., Dunnagan, R., Saha, S.P., Ferraris, V.A. & Xenos, E.S. (2013). Intraoperative blood transfusion of one or two units of packed red blood cells is associated with a fivefold risk of stroke in patients undergoing elective carotid endarterectomy. Journal of Vascular Surgery, 57(Suppl. 2), 53S–57S. doi:10.1016/j.jvs.2012.07.059 [CrossRef]
- Serrano-Trenas, J.A., Ugalde, P.F., Cabello, L.M., Chofles, L.C., Lázaro, P.S. & Benítez, P.C. (2011). Role of perioperative intravenous iron therapy in elderly hip fracture patients: A single-center randomized controlled trial. Transfusion, 51, 97–104. doi:10.1111/j.1537-2995.2010.02769.x [CrossRef]
- Shaw, R.E., Johnson, C.K., Ferrari, G., Zapolanski, A., Brizzio, M., Rioux, N. & Grau, J.B. (2013). Balancing the benefits and risks of blood transfusions in patients undergoing cardiac surgery: A propensity-matched analysis. Interactive Cardiovascular and Thoracic Surgery, 17, 96–102. doi:10.1093/icvts/ivt124 [CrossRef]
- Society for the Advancement of Blood Management. (2017). What is patient blood management. Retrieved from http://www.sabm.org
- Thein, M., Ershler, W.B., Artz, A.S., Tecson, J., Robinson, B.E., Rothstein, G. & Robbins, S. (2009). Diminished quality of life and physical function in community-dwelling elderly with anemia. Medicine, 88, 107–114. doi:10.1097/MD.0b013e31819d89d5 [CrossRef]
- van Boven, W.-J.P., Gerritsen, W.B., Driessen, A.H., van Dongen, E.P., Klautz, R.J. & Aarts, L.P. (2013). Minimised closed circuit coronary artery bypass grafting in the elderly is associated with lower levels of organ-specific biomarkers: A prospective randomised study. European Journal of Anaesthesiology, 30, 685–694. doi:10.1097/EJA.0b013e328364febf [CrossRef]
- Vochteloo, A.J., Borger van der Burg, B.L., Mertens, B., Niggebrugge, A.H., de Vries, M.R., Tuinebreijer, W.E. & Pilot, P. (2011). Outcome in hip fracture patients related to anemia at admission and allogeneic blood transfusion: An analysis of 1262 surgically treated patients. BMC Musculoskeletal Disorders, 12, 262. doi:10.1186/1471-2474-12-262 [CrossRef]
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Bias Assessment Tool
|Title and Abstract|
|Indicates the manuscript concerns an initiative to improve healthcare||Yes (0)||No (1)|
|A) Provide adequate information to aid in searching and indexing||A) Yes (0)||No (1)|
|B) Summarize all key information from various sections of the text||B) Yes (0)||No (1)|
|Nature and significance of the local problem||Yes (0)||No (1)|
|Summary of what is currently known about the problem, including relevant previous studies||Yes (0)||No (1)|
|Informal or formal frameworks, models, concepts, and/or theories used to explain the problem||Yes (0)||No (1)|
|Purpose of the project and of this report||Yes (0)||No (1)|
|Contextual elements considered important at the outset of introducing the intervention(s)||Yes (0)||No (1)|
|A) Description of the intervention(s) in sufficient detail that others could reproduce it||A) Yes (0)||No (1)|
|B) Specifics of the team involved in the work||B) Yes (0)||No (1)|
|A) Approach chosen for assessing the impact of the intervention(s)||A) Yes (0)||No (1)|
|B) Approach used to establish whether the observed outcomes were due to the intervention(s)||B) Yes (0)||No (1)|
|A) Measures chosen for studying processes and outcomes of the intervention(s)||A) Yes (0)||No (1)|
|B) Description of the approach to the ongoing assessment of contextual elements||B) Yes (0)||No (1)|
|C) Methods employed for assessing completeness and accuracy of data||C) Yes (0)||No (1)|
|A) Qualitative and quantitative methods used to draw inferences from the data||A) Yes (0)||No (1)|
|B) Methods for understanding variation within the data, including the effects of time||B) Yes (0)||No (1)|
|Ethical Considerations||Ethical aspects of implementing and studying the intervention(s) and how they were addressed, including, but not limited to, formal ethics review and potential conflict(s) of interest||Yes – present and sufficient (0)||No – not present; present but not sufficient (1)|
|Results||A) Initial steps of the intervention(s) and their evolution over time (e.g., time-line diagram, flow chart, or table), including modifications made to the intervention during the project||A) Yes (0)||No (1)|
|B) Details of the process measures and outcome||B) Yes (0)||No (1)|
|C) Contextual elements that interacted with the intervention(s)||C) Yes (0)||No (1)|
|D) Observed associations between outcomes, interventions, and relevant contextual elements||D) Yes (0)||No (1)|
|E) Unintended consequences such as unexpected benefits, problems, failures, or costs associated with the intervention(s)||E) Yes (0)||No (1)|
|F) Details about missing data||F) Yes (0)||No (1)|
|Summary||A) Key findings, including relevance to the rationale and specific aims||A) Yes (0)||No (1)|
|B) Particular strengths of the project||B) Yes (0)||No (1)|
|Interpretation||A) Nature of the association between the intervention(s) and the outcomes||A) Yes (0)||No (1)|
|B) Comparison of results with findings from other publications||B) Yes (0)||No (1)|
|C) Impact of the project on people and systems||C) Yes (0)||No (1)|
|D) Reasons for any differences between observed and anticipated outcomes, including the influence of context||D) Yes (0)||No (1)|
|E) Costs and strategic trade-offs, including opportunity costs||E) Yes (0)||No (1)|
|Limitations||A) Limits to the generalizability of the work||A) Yes (0)||No (1)|
|B) Factors that might have limited internal validity such as confounding, bias, or imprecision in the design, methods, measurement, or analysis||B) Yes (0)||No (1)|
|C) Efforts made to minimize and adjust for limitations||C) Yes (0)||No (1)|
|Conclusions||A) Usefulness of the work||A) Yes (0)||No (1)|
|B) Sustainability||B) Yes (0)||No (1)|
|C) Potential for spread to other contexts||C) Yes (0)||No (1)|
|D) Implications for practice and for further study in the field||D) Yes (0)||No (1)|
|E) Suggested next steps||E) Yes (0)||No (1)|
|Funding||Sources of funding that supported this work. Role, if any, of the funding organization in the design, implementation, interpretation, and reporting||Yes (0)||No (1)|
|Reference||Purpose||Sample and Setting||Major Variables Studied and Definitions||Measurement||Data Analysis||Findings||Conclusions||Bias Score|
|Serrano-Trenas et al. (2011)||Determine if perioperative IV iron sucrose therapy reduced transfusion requirements in elderly patients undergoing hip fracture surgery||200 patients aged over 65 years undergoing hip fracture surgery (Spain)||Number and rate of patients transfused postoperatively; mean number PRBC units per patient||Transfusion of PRBC units pre- and postoperatively; type and duration of surgery; respiratory, urinary, or surgical-wound infections; length of stay; mortality; potential side effects of the IV therapy||Descriptive statistics (chi-square, Fisher's test, t-test), analysis of variance; intent-to-treat analysis||Fewer patients in the IV therapy group received PRBC transfusion compared to the control group (33% vs 41%), though this was not significant
For patients with intracapsular fractures, fewer patients received transfusions in the IV therapy group compared with the control group (14% vs 46%, p=.004); patients in the IV therapy group who were transfused received on average fewer PRBC units compared to those in the control group who were transfused (.3 units vs .9 units, p<.05)||IV iron sucrose therapy reduced perioperative transfusion requirements among elderly patients undergoing intracapsular hip fracture surgery when baseline hemoglobin is 12 g/dL or higher.||13|
|Greiff et al. (2012)||Evaluate the use of tranexamic acid to reduce blood transfusion in elderly undergoing cardiac surgery||64 elderly patients (70 or older) undergoing combined aortic valve replacement and CABG (Norway)||Effect of tranexamic acid vs saline placebo on blood loss and transfusion requirements||Postoperative blood loss measured every four hours for 16 hours; incidents of re-exploration required; blood transfusions recorded during the entire hospital stay (no blood loss measured during surgery)||Descriptive statistics (t-test, Mann-Whitney U), analysis of variance||Patients in the tranexamic acid group experienced less blood loss (695, IQR 470–1590 mL vs 1035, IQR 517–1485, p = 0.36) and received fewer PRBC units (3, IQR 2–5 vs 5, IQR 3–7, p = 0.049)||Tranexamic acid did not significantly reduce postop bleeding, but may reduce the need for PRBC transfusion among elderly undergoing cardiac surgery.||8|
|Kiessling et al. (2012)||Determine the safety and efficacy of pre-filling of extracoporeal circuit of heart-lung machine with autologous blood vs standard of care||72 patients older than 75 years undergoing surgery requiring cardiopulmonary bypass (Germany)||Blood product transfusion requirement, specifically in the postoperative period||Number of erythrocyte concentrates, thrombocyte concentrates, fibrinogen, prothrombin concentrates, and FFP transfused from the preoperative period until discharge||Descriptive statistics (t-test, chi-square), analysis of variance, logistic regression||No significant differences in PRBC (control 900 ± 780 mL vs pre-coat 730 ± 750 mL), platelets (control 60 ± 80 mL vs pre-coat 40 ± 80 mL), fresh frozen plasma (control 150 ± 450 vs pre-coat 240 ± 630) requirements||Pre-coating with autologous blood had no influence on postoperative transfusion requirements.
Patient age, bypass time, and intra-hospital length of stay were significant risk factors for postoperative transfusion requirement.||10|
|Yu et al. (2012)||Compare hemostatic efficacy and feasibility of direct injection of bone wax vs fibrin sealant into sternotomy cavities||82 patients over age 65 undergoing procedures through median sternotomy incision and on-pump CABG (China)||Hemostasis||Blood loss in first 24 hours after surgery, total blood loss, blood product administration, intubation time, ICU/hospital length of stay, and postoperative complications (reoperation, mediastinitis, hemothorax, and wound infection)||Descriptive statistics (t-test, chi-square)||40 patients in bone wax group (18 men, mean age 70 ± 4 years); 42 patients in fibrin sealant group (23 men, mean age 71 ± 7 years)
Blood loss in first 24 hours reduced in fibrin sealant group compared with bone wax group (186.67 ± 49.53 vs 333.75 ± 60.49 mL, p < 0.001)
Total blood loss also reduced in fibrin sealant group (326.19 ± 67.24 vs 516 ± 8.46 mL, p < 0.001)
Patients in fibrin sealant group received 3.6 ± 1.25 units PRBC vs pts in bone wax who received 7.4 ± 2.13 units PRBC (p < 0.001)||Fibrin sealant may reduce blood loss compared to use of bone wax in older adults who undergo procedures that require sternotomy.||19|
|Okazaki et al. (2013)||Evaluate the use of perioperative synbiotic therapy on reducing infectious complications in elderly patients undergoing gastroenterological surgery||48 patients (70 or older) with gastrointestinal and hepatobillary pancreatic cancers scheduled to undergo surgery (Japan)||Effect of pre- and postoperative synbiotics vs no synbiotics with on reduction of infectious complications after surgery||Changes in fecal microbiota and fecal acids pre-operatively and postoperatively on days 7 & 14||Descriptives (chi-square, Mann-Whitney U), stepwise logistic regression||Pre-operative blood transfusion was an independent risk factor for developing an infectious complication (OR = 6.476, 95% CI, 1.179–35.58, P = 0.032)||Synbiotic therapy did not significantly reduce the risk of infection but transfusions did significantly increase the risk of post-op infections.||14|
|van Boven et al. (2013)||Evaluate the efficacy of restrictive fluid management on improving post-operative outcomes, including organ function, in elderly patients undergoing cardiac surgery||60 patients (70 or older) undergoing first time CABG surgery (The Netherlands)||Cardiac, respiratory and abdominal organ injury as well as blood product consumption||Myocardial, intestinal, and hepatic injury biomarkers, and need for PRBC transfusion||Friedman test, Fisher's exact test and Pearson chi-square||Following mCABG with low volume myocardial preservation and restrictive fluid management, early respiratory performance was improved and consumption of blood products reduced compared with opCAB and cCABG||Fluid restriction during mCABG resulted in better maintenance of physiological balances and decreased blood product consumption.||15|
|Fan et al. (2014)||Compare the impact of a restrictive (Hb < 8.0 g/dL) vs liberal (Hb < 10.0 g/dL) transfusion strategy on development of postoperative delirium||186 patients older than 65 years undergoing elective unilateral hip replacement (China)||Development of delirium||Cognition evaluated preoperatively using the Mini-Mental State Exam; delirium was diagnosed postoperatively using the confusion assessment method for the intensive care unit (CAM-ICU)||Descriptives (t-test, chi-square, Fisher's exact, Mann-Whitney U), analysis of variance||No difference in development of delirium among those in restrictive transfusion vs liberal transfusion group (21.3% vs 23.9%, p > 0.05)||Restrictive transfusion not associated with higher incidence of delirium postop in aged patients undergoing hip replacement with spinal anesthesia.
Use of restrictive transfusion strategy supported as safe and effective among aged patients undergoing hip replacement surgery.||10|
|Gergersen, Borris, & Damsgaard (2015a)||Compare effects of restrictive (Hb < 9.7 g/dL; <6 mmol/L) or liberal (Hb < 11.3 g/dL; < 7 mmol/L) PRBC transfusion strategy on postoperative outcomes||157 frail older adults (65 and over) undergoing unilateral hip fracture repair (Denmark)||Effect of transfusion strategy on QOL, depression and ADL||QOL, depression and ADL levels 30 days and one year after surgery among transfusion strategy groups||Descriptives (Student's t-test, chi-square), Wilcoxon rank sum test, linear regression||QOL and depression scores not significantly different for the restrictive and liberal transfusion groups at 30 day and one year follow up
ADL scores were statistically greater for the liberal group than for the restrictive group (p=0.03)||Liberal PRBC transfusions may improve ADL recovery following surgery for hip fracture for frail older adults.||17|
|Gregersen, Borris, & Damsgaard (2015b)||Evaluate the association among restrictive (Hb < 9.7 g/dL; <6 mmol/L) vs liberal (Hb < 11.3 g/dL; < 7 mmol/L) PRBC transfusion strategy and physical recovery or morality||284 frail older adults (65 and older) undergoing unilateral hip fracture repair (Denmark)||Degree of physical recovery and mortality rate||PRBC transfusions (restrictive vs liberal strategy) given within the first 30 days postoperatively; follow-up measuring physical recovery and mortality at 90 days||Descriptives (Student's t-test, Pearson's chi-square, Fisher's exact test), Wilson's rank-sum test, analysis of variance, likelihood ratio tests, Cox proportional hazard regression||Risk of 30-day mortality was higher with the restrictive group (HR = 2.4, 95% CI: 1.1–5.2; p=0.03), as was 90-day mortality (HR = 2.0, 95% CI: 1.1–3.6; p=0.01).||Implementation of a liberal PRBC transfusion strategy in nursing home residents may have the potential to increase survival after hip fracture surgery.||12|
|Gregersen, Damsgaard, & Borris (2015)||Evaluate the association among restrictive (Hb < 9.7 g/dL; <6 mmol/L) vs liberal (Hb < 11.3 g/dL; < 7 mmol/L) PRBC transfusion strategy and postoperative infection risk||227 frail older adults (65 and older) undergoing unilateral hip fracture repair (Denmark)||Mean leukocyte concentration and mean C-reactive protein concentrations||Leukocytes and C-reactive protein in repeated blood samples within 30 days; number of all infections (pneumonia, urinary tract infection, and other infections) within 10 days||Descriptives (Student's t-test, Pearson's chi-square), Wilson's rank-sum test, analysis of variance, likelihood ratio tests, relative risk ratios, logistic regression||72% of the patients in the restrictive transfusion group developed an infection compared to 66% of those in the liberal group (RR: 1.08; 95% CI: 0.93–1.27; p=0.29)||A liberal transfusion strategy is not associated with a higher risk of infection among older adults undergoing hip fracture repair.||11|