What this is
- This study investigates the impact of intra-operative blood transfusions () on postoperative outcomes in elderly patients with hip fractures.
- It specifically examines the incidence of () and functional recovery following surgery.
- The analysis includes a cohort of patients aged 65 and older, using propensity score matching to reduce bias.
Essence
- significantly increases the risk of and impairs functional recovery in elderly hip fracture patients.
Key takeaways
- correlates with a higher incidence of , with rates of 13.42% in the group vs. 7.72% in the non- group. This suggests that blood transfusions during surgery may exacerbate cognitive complications in elderly patients.
- Functional outcomes are negatively impacted by , as indicated by a significant association between and poorer postoperative recovery metrics.
Caveats
- The study's retrospective design may limit the ability to establish causation between and postoperative outcomes.
- Potential confounding variables were addressed using propensity score matching, but unmeasured confounders may still exist.
Definitions
- Postoperative Delirium (POD): Acute confusion and cognitive impairment occurring after surgery, common in elderly patients.
- Intra-operative Blood Transfusion (IBT): The administration of blood products during surgical procedures to address blood loss.
AI simplified
Introduction
Postoperative delirium (POD) is a prevalent central nervous system complication observed in elderly patients following anesthesia and surgery [1]. It is characterized by the onset of acute delirium and subsequent long-term cognitive impairment, manifesting as mental confusion, anxiety, personality alterations, and memory deficits [2]. A multi-center retrospective study shows that individuals aged 65 and older experience POD 4–10 times more frequently than younger patients [3, 4]. Additionally, those aged 75 and older have a threefold higher incidence of POD compared to those aged 65–75 [5]. POD not only poses an elevated risk of enduring cognitive impairment and dementia among elderly patients, but also hampers their postoperative recovery, thereby imposing substantial economic and psychological burdens on both the patients and their families [6]. With the increasing elderly population and improved surgical and anesthesia methods, more elderly patients are undergoing surgeries with general anesthesia. As a result, POD and its complications have become significant medical and social issues, making the study of its pathogenesis and prevention in older adults a key research focus [7].
Despite the current lack of complete understanding regarding the etiology of POD, a substantial body of research has consistently demonstrated a strong association between increasing age, nursing home residency, pre-existing cognitive impairment, and higher American Society of Anesthesiologists (ASA) score with the occurrence of POD [8]. The prevalence of hip fractures, particularly intertrochanteric fractures, has been escalating due to the aging population and rising incidence rates, surpassing one million cases annually, particularly in developing nations [9, 10]. Consequently, hip fractures have emerged as the predominant cause of admission in orthopedic wards catering to elderly patients. As a result of numerous postoperative complications and challenges in attaining favorable outcomes, intertrochanteric fractures of the femur have emerged as a prominent public health concern among the elderly, imposing significant social and economic burdens on society [11, 12].
A recent study found that elderly patients with hip fractures require more frequent and larger intraoperative blood transfusions than other surgical groups [13]. This is due to pre-existing anemia, either present before the fracture or caused by blood loss from the fracture, and significant blood loss during procedures like reduction and fixation. Elderly individuals typically have reduced vascular elasticity and face difficulties with hemostasis [14]. They often suffer from osteoporosis and various cardiovascular and cerebrovascular conditions. Surgical treatment of fractures requires stronger internal fixation devices, like screws or steel plates, which increases surgery time and blood loss. Therefore, elderly patients with hip fractures often experience POD after surgery [11, 15]. Prompt administration of blood transfusions can enhance oxygenation capacity and sustain circulatory stability in elderly patients undergoing surgery. Nevertheless, excessive transfusion of stored blood may lead to microcirculatory dysfunction and a higher likelihood of postoperative complications. Additionally, the infusion of allogeneic blood can impede the immune regulatory function of the body, elevate the risk of myocardial ischemia, and prolong hospitalization duration [16]. Thus, we speculate that there may be a close relationship between intraoperative blood transfusion (IBT) and POD in elderly patients. Taken together, the objective of this study is to assess the impact of IBT on postoperative outcomes, including incidence of POD, length of hospital stay (LOS), functional outcomes, and mortality, in older individuals with hip fractures. The findings of this research will offer valuable insights for selecting appropriate timing for perioperative blood transfusion in elderly patients.
Materials and methods
This retrospective study received approval from the Ethics Committee of our hospital and was registered on the Clinical Trial Registry Center. The study was conducted in compliance with the principles outlined in the Declaration of Helsinki, and consent was waived as this is an observational study without an intervention. All collected patient data were anonymously recorded to protect patient confidentiality.
Study design, setting, and population
A retrospective analysis of IF patients was conducted at the National trauma emergency center between Jan. 2018 and Dec. 2021. The inclusion criteria for this study consisted of patients who were 65 years or older, had an ASA grade I ~ III, experienced an admission delay of less than 48 h from the initial injury, and received a minimum of 12-month follow-up. The exclusion criteria included patients with a history of central nervous system disease (such as transient ischemic attack, stroke, cerebral hemorrhage, syncope, spinal cord injury, or upright hypotension), electrolyte disturbance (including hypernatremia, hypokalemia, and hyperchloremia), a history of neurological or psychiatric disorder, currently using sedatives or antidepressants, experiencing infection or chronic inflammation, recently taking anti-inflammatory drugs, unwilling to participate in experimental procedures, suffering from speech impairment, illiteracy, hearing impairment, visual disorder, alcohol or drug addiction, or having an allergic reaction to anesthetic drugs. The patients were categorized into either the IBT or non-IBT groups based on whether they received IBT during the surgical procedure. All IBT types are packed RBCs. Patients who received autologous blood transfusion were not included in this study.
Anesthetic management and surgical procedure
Upon the patient's entrance into the operating room, continuous monitoring of non-invasive blood pressure, pulse oxygen saturation, and electrocardiogram was conducted. Additionally, patients received a continuous inhalation of oxygen at a rate of 2 L/min via a face mask. Intraspinal anesthesia was administered in accordance with the standard protocol.
Preoperative X-rays, including anteroposterior and lateral views, as well as a Siemens 128-layer dual-source spiral CT scan (Siemens Medical System, Germany), were obtained for the injured leg. Fractures were categorized as either stable (A1.1-A2.1) or unstable (A2.2-A3.3) based on the classification system established by the Orthopaedic Trauma Association [17]. The patients underwent surgical treatment with intramedullary fixation by proximal femoral nail antirotation (PFNA), in accordance with international treatment guidelines. During the surgical procedure, the internal fixation was meticulously assessed, and the wound was subsequently sutured in a layered manner. Postoperatively, the patients were advised to gradually increase weight-bearing activities, ranging from partial to full weight bearing. To ensure proper monitoring, regular outpatient reviews or telephone interviews were conducted with either the patients themselves or their family members.
Data collection
Data were collected retrospectively from the electronic medical record of our institution. The collected data encompassed various patient demographics such as gender, age, body mass index (BMI), residence (rural or urban), and history of smoking or alcohol use. Additionally, injury-related data included fracture type and the duration from initial injury to surgery. Surgery-related data consisted of general health status determined by the ASA grade and modified Elixhauser comorbidity measures (mECM). Lastly, inhospital data encompassed the Hb level, commonly used visual analog scores (VAS), and numerical rating scores (NRS) upon admission. Operation-related data, such as the duration of anesthesia and the duration of the operation, were collected. In-hospital outcomes, including the VAS, NRS, LOS, and incidence of POD using the Method-Chinese Revision (CAM-CR) score, were also recorded. The participants' survival status and date of death were collected during the follow-up period. The beginning of the follow-up period was defined as enrollment in the cohort, and the endpoint event was defined as death from any cause or the most recent follow-up visit, whichever occurred earlier. Additionally, 30-day, 90-day, and 12-month mortality rates, as well as functional outcomes such as independent walking, use of walking aids, wheelchair, bedridden status, and death, were also documented.
Definitions
In this current study, the mECM derived from electronic medical records was employed to evaluate the comorbidities of patients upon admission, and subsequently categorized into groups < 0, 0, 1–5, 6–13, and ≥ 14. Furthermore, the ASA grade, which encompasses four levels, is a widely utilized assessment tool by anesthesiologists and orthopedics to evaluate a patient's physical state and surgical risk [18]. The 15-item Geriatric Depression Scale (GDS) and functional independence measure (FIM) were utilized to ascertain depression symptoms and the overall capacity to carry out daily activities, respectively [19, 20]. Investigators, blinded to patient subgroups and pre-trained, conducted return visits to apply the CAM-CR scale twice daily (8:00–10:00 a.m. and 6:00–8:00 p.m.) for 1–3 days postoperatively to assess POD. The CAM-CR score assesses 11 items: acute onset, attentional disturbance, disturbed thinking, altered awareness, disorientation, memory disturbance, perceptual impairment, psychomotor arousal and retardation, fluctuation, and sleep–wake cycle changes. Each item is rated from 1 (none) to 4 (severe), resulting in a total score between 11 and 44. A score above 22 indicates delirium.
Statistical Analysis
To assess normality of continuous variables, the Shapiro–Wilk test was employed. For normally distributed numerical variables, the Student t test was utilized to determine group mean differences, with data presented as mean ± standard deviation (SD). In cases where data were non-normally distributed, the median and interquartile range (IQR) were reported and analyzed using the Mann–Whitney U test. Categorical variables were presented as proportions and differences were examined using either the chi-square or Fisher's exact test. In order to mitigate selection bias and potential confounding factors, propensity score matching (PSM) was employed to adjust for baseline clinical characteristics at a 1:1 ratio, with a caliper matching of 0.20. Following PSM, paired t-tests and paired chi-square tests were utilized to analyze continuous and categorical variables, respectively. Additionally, Spearman correlations were computed to examine the relationship between IBT, VAS, NRS, and relevant influencing factors. All statistical analyses were conducted using IBM SPSS Statistics for Windows, version 27.0 (IBM, Armonk, NY, USA). The level of significance was determined at P < 0.05.
Results
Demographic characters of patients
Flow diagram of the participants
| Variables | Pre-matching | Post-matching | ||||
|---|---|---|---|---|---|---|
| IBT group(n = 403) | non-IBT group(n = 1278) | valueP | IBT group(n = 298) | non-IBT group (n = 298) | valueP | |
| Demographics | ||||||
| Gender [(n) %] | 0.472 | 0.667 | ||||
| Male | 145 (35.98%) | 408 (31.92%) | 107 (35.91%) | 102 (34.22%) | ||
| Female | 258 (64.02%) | 870 (68.08%) | 191 (64.09%) | 196 (65.88%) | ||
| Age (yr) | 79.86 ± 7.28 | 78.92 ± 7.33 | 0.619 | 79.26 ± 7.28 | 79.38 ± 7.28 | 0.703 |
| BMI (kg/m)2 | 25.37 ± 2.65 | 25.84 ± 2.88 | 0.668 | 25.66 ± 2.69 | 25.63 ± 2.65 | 0.849 |
| Residence (%) | 0.027 | 0.589 | ||||
| Rural | 142 (35.24%) | 524 (41.00%) | 109 (36.58%) | 110 (36.91%) | ||
| Urban | 261 (64.76%) | 754 (59.00%) | 189 (63.42%) | 188 (61.71%) | ||
| Smoking history [Yes (n) %] | 91 (22.58%) | 226 (17.68%) | 0.256 | 59 (19.80%) | 55 (18.46%) | 0.519 |
| Drinking history [Yes (n) %] | 103 (25.56%) | 294 (23%) | 0.189 | 239 (81.20%) | 243 (81.54%) | 0.726 |
| Injury-related data | ||||||
| Fracture type [(n) %] | 0.013 | 0.476 | ||||
| Stable (A1.1-A2.1) | 187 (46.4%) | 712 (55.71%) | 150 (50.33%) | 154 (51.68%) | ||
| Unstable (A2.2-A3.3) | 216 (53.6%) | 566 (44.29%) | 148 (49.66%) | 143 (48.32%) | ||
| Time from injury to surgery (day) | 6.01 ± 2.43 | 6.2 ± 2.04 | 0.658 | 6.07 | 6.13 | 0.889 |
| Surgery-related data | ||||||
| ASA grade [(n) %] | 0.289 | 0.883 | ||||
| I | 64 (15.88%) | 250 (19.56%) | 48 (16.11%) | 51 (17.11%) | ||
| II | 174 (43.18%) | 483 (37.79%) | 119 (39.93%) | 117 (39.26%) | ||
| III | 165 (40.94%) | 545 (42.65%) | 131 (43.96%) | 130 (43.62%) | ||
| mECM | 0.57 | 0.773 | ||||
| < 0 | 12 (2.98%) | 48 (3.76%) | 9 (3.02%) | 10 (3.36%) | ||
| 0 | 197 (48.88%) | 663 (51.88%) | 146 (48.99%) | 147 (49.32%) | ||
| 1–5 | 58 (14.39%) | 167 (13.07%) | 42 (14.09%) | 40 (13.42%) | ||
| 6–13 | 107 (26.55%) | 350 (27.39%) | 80 (26.85) | 81 (27.18) | ||
| ≥ 14 | 29 (7.22%) | 50 (3.91%) | 21 (7.05%) | 20 (6.71%) | ||
| In-hospital data | ||||||
| Preoperative Hb level (g/dL) | 9.38 ± 2.12 | 9.97 ± 2.30 | 0.786 | 9.62 ± 2.23 | 9.68 ± 2.29 | 0.819 |
| Preoperative VAS score | 5.32 ± 1.68 | 6.29 ± 1.76 | 0.381 | 5.78 ± 1.69 | 5.97 ± 1.71 | 0.768 |
| GDS | 4.86 ± 1.37 | 4.03 ± 1.24 | 0.389 | 4.57 ± 1.33 | 4.51 ± 1.27 | 0.882 |
| FIM | 81.69 ± 9.85 | 86.98 ± 10.65 | 0.019 | 83.26 ± 9.89 | 84.39 ± 10.0 | 0.773 |
| Variables | Pre-matching | Post-matching | ||||
|---|---|---|---|---|---|---|
| IBT group(= 403)n | Non-IBT group(= 1278)n | valueP | IBT group(= 298)n | Non-IBT group (= 298)n | valueP | |
| Duration of operation (Mins) | 96.58 ± 15.16 | 100.1 ± 19.37 | 0.493 | 98.46 ± 35.92 | 98.86 ± 36.01 | 0.887 |
| VAS at discharge | 2.98 ± 0.89 | 2.37 ± 0.61 | 0.043 | 2.67 ± 1.65 | 2.70 ± 1.68 | 0.849 |
| NRS at discharge | 15.39 ± 2.88 | 16.03 ± 3.02 | 0.038 | 14.6 ± 6.98 | 14.8 ± 7.02 | 0.739 |
| LOS (day) | 15.1 ± 2.74 | 14.6 ± 2.28 | 0.376 | 14.9 ± 5.92 | 14.8 ± 5.98 | 0.876 |
| POD (Yes) | 41 (9.93%) | 106 (8.29%) | 0.864 | 40 (13.42%) | 23 (7.72%) | < 0.001 |
| 30-day mortality | 4 (0.99%) | 16 (1.25%) | 0.658 | 4 (1.34%) | 3 (1.01%) | 0.927 |
| 90-day mortality | 6 (1.49%) | 22 (1.72%) | 0.744 | 5 (1.68%) | 4 (1.34%) | 0.869 |
| 12-month mortality | 28 (6.95%) | 92 (7.20%) | 0.813 | 21 (7.05%) | 20 (6.71%) | 0.902 |
| Functional outcomes [(n) %] | 0.749 | 0.029 | ||||
| Independent walking | 161 (39.95%) | 512 (40.06%) | 119 (39.93%) | 132 (44.30%) | ||
| Use of walking aids | 120 (29.78%) | 384 (30.05%) | 89 (29.87%) | 104 (34.90%) | ||
| Use of wheelchair | 21 (5.21%) | 64 (5.01%) | 15 (5.03%) | 10 (3.36%) | ||
| Bedridden | 21 (5.21%) | 71 (5.56%) | 16 (5.37%) | 7 (2.35%) | ||
| Death | 80 (19.85%) | 247 (19.33%) | 59 (19.80%) | 45 (15.10%) | ||
| Variables | IBT group(= 298)n | Non-IBT group (= 298)n | Spearman’sstatisticr | valueP |
|---|---|---|---|---|
| LOS (day) | 14.9 ± 5.92 | 14.8 ± 5.98 | ||
| POD (Yes) | 40 (13.42%) | 23 (7.72%) | − 0.29 | 0.006 |
| 30-day mortality | 3 (1.01%) | 4 (1.34%) | 0.324 | 0.237 |
| 90-day mortality | 4 (1.34%) | 5 (1.68%) | 0.297 | 0.335 |
| 12-month mortality | 20 (6.71%) | 21 (7.05%) | 0.419 | 0.417 |
| Functional outcomes [() %]n | − 0.28 | 0.013 | ||
| Independent walking | 119 (39.93%) | 132 (44.30%) | ||
| Use of walking aids | 89 (29.87%) | 104 (34.90%) | ||
| Use of wheelchair | 15 (5.03%) | 10 (3.36%) | ||
| Bedridden | 16 (5.37%) | 7 (2.35%) | ||
| Death | 59 (19.80%) | 45 (15.10%) |
Discussion
POD is a prevalent complication and a significant contributor to post-surgical mortality, particularly in the context of hip surgery. Several studies have reported varying rates of POD among the elderly population in Asian countries, ranging from 2 to 7%, with even higher rates exceeding 50% following hip fracture repair [21, 22]. In a comprehensive multicentre observational study conducted by Unal D, it was found that 25.8% of patients received a peri-operative transfusion [16]. Despite efforts made by scholars to investigate the association between IBT and POD, the presence of numerous confounding variables within the data poses challenges to the validity and reliability of the results. In this study, data was gathered from a sample of 1681 patients, and PSM analysis was employed to investigate the association between IBT and POD. These findings indicate a significant correlation between IBT and an elevated occurrence of POD, it further hinders the postoperative functional recuperation of elderly patients with hip fracture.
Hip fractures in the elderly are a prevalent form of fracture, typically resulting from factors such as osteoporosis or unintentional falls among this demographic. The surgical intervention for hip fractures in the elderly entails a substantial procedure involving surgical trauma, anesthesia, intraoperative blood loss, pain, and other stimuli, all of which have the potential to induce postoperative delirium in patients [11, 23]. Furthermore, elderly patients frequently experience cognitive and memory decline, rendering them more susceptible to anxiety, fear, and other emotional responses when confronted with surgery and postoperative pain, consequently elevating the risk of adverse outcomes [24]. Geriatric individuals frequently present with prevalent underlying medical conditions, including hypertension, diabetes, and coronary heart disease, among others, which can potentially contribute to the development of postoperative delirium [25, 26].
Due to the pathological and physiological characteristics of elderly patients, blood transfusion is often required during surgery. However, the efficacy of intraoperative blood transfusion is not universally advantageous. The occurrence of postoperative cognitive impairment may be attributed to diminished cerebral blood flow, metabolic dysfunction, and an inflammatory reaction during surgical procedures. Remy KE et al. have posited that the administration of red blood cells can elicit a dual impact, both inhibiting and promoting inflammatory responses within the organism [27]. Similarly, Hensler et al. have suggested that the transfusion of blood products in patients with multiple injuries can activate cytokines and inflammatory mediators, such as tumor necrosis factor α and Interleukin-6, within the body [28]. Despite the limited number of clinical trials investigating the correlation between blood transfusion and postoperative delirium in elderly patients with hip fractures, it is noteworthy that no previous study has exclusively examined this association in the elderly population. Nevertheless, an Umbrella review encompassing 35 pertinent literature pieces indicates that intraoperative blood transfusion could potentially serve as an autonomous risk factor for postoperative delirium [29]. To consolidate the data, our study employed propensity score matching analysis. This study demonstrates a significant association between IBT and the occurrence of POD. The findings indicate that the incidence of POD is significantly increased with the administration of IBT. Moreover, the correlation analysis supports the consistent conclusion drawn from previous research.
With the progression of society and the elongation of human lifespan, population aging has emerged as a worldwide phenomenon. Due to the prevalence of osteoporosis among the elderly, the decline in bodily functions, and inadequate protection of hip joint muscles, even minor injuries can lead to hip fractures, resulting in a high incidence rate among the elderly. Consequently, the factors influencing postoperative functional recovery of the hip have consistently garnered attention from orthopedic physicians. Research has revealed that age, BMI, ASA grading, and anesthesia methods all serve as independent risk factors that impact the postoperative recovery of patients [30]. The frequency of intraoperative blood transfusion is intricately linked to the extent of preoperative anemia, intraoperative hemorrhage, and the patient's vital signs. While orthopedic and anesthesiologists continue to debate the optimal approach for blood transfusion during surgery for elderly patients with hip fractures, Leuzinger et al. have suggested that intraoperative blood transfusion may elevate the occurrence of postoperative pulmonary complications and prolong hospitalization in this patient population, albeit without impacting postoperative mortality rates [31].
Numerous scholarly works have examined the utilization of intra-operative blood transfusion as a means to address perioperative anemia in patients with hip fractures [31]. These studies have demonstrated a positive correlation between such transfusions and a reduction in POD rates [29], while also highlighting their potential negative impact on functional outcomes [32, 33]. Nevertheless, none of these investigations have accounted for potential confounding variables when reporting their findings. Thus, PSM analysis was applied in the current study to mitigate the impact of bias and confounding variables in the data, facilitating more valid comparisons between the experimental and control groups. Additionally, PSM analysis aids in data balancing and mitigates statistical errors arising from data imbalance. Our findings, derived from PSM analysis, reveal significant disparities in delirium rates and functional outcomes, even in the absence of notable distinctions between the initial two groups in terms of machinery. Recent studies have revealed that blood transfusion can potentially give rise to avoidable hazards or unfavorable responses, including circulatory overload, diminished cardiac output, acute renal impairment, hemolytic transfusion reactions, allergic responses, antibody production, infection, and mortality [34, 35]. Several research reports indicate that, in older patients who have undergone hip fracture surgery or have a higher cardiovascular risk, free transfusion strategies (transfusions with higher hemoglobin levels) do not result in reduced mortality or improved physical function recovery after discharge, when compared to restrictive transfusion strategies (transfusions based on hemoglobin levels). Our research findings also confirm that intraoperative blood transfusion significantly reduces the degree of functional recovery in elderly patients with hip fractures after surgery, and increases which consists with the current study [36].
It is evident that this study possesses certain limitations. Firstly, Due to its excellent analgesic effect and high patient acceptance rate, spinal anesthesia is a commonly used anesthesia method for elderly patients with intertrochanteric fractures. In order to eliminate the interference of anesthesia methods on experimental results, we only included elderly patients who received spinal anesthesia in this study. Secondly, the analysis was solely retrospective, encompassing a sample size of 1681 elderly patients with hip fractures within our unit over a four-year period. Consequently, findings derived from studies conducted over longer durations and across multiple centers may yield more compelling results. Thirdly, we did not undertake a stratified analysis to examine the correlation between the quantity of intraoperative blood transfusion and the occurrence of postoperative delirium in a systematic manner. Finally, we did not explore the potential impacts of preoperative blood transfusion and intraoperative infusion of other blood products, such as platelets, plasma, and cryoprecipitates.
Conclusion
In conclusion, IBT seems to increase the risk of POD and hinder functional recovery in elderly patients with hip fracture. Further studies should focus on choosing the appropriate timing for blood transfusion for such patients to achieve better postoperative outcomes.