Introduction
Anaemia is defined as a reduced haemoglobin content of the blood or a lack of erythrocytes. According to the World Health Organization (WHO), anaemia, the thresholds for which were published in 1968 [
1], can be triggered by the following events: increased loss of erythrocytes (blood loss); reduced production of erythrocytes; increased destruction of erythrocytes; or an increased physiological need for erythrocytes [
2]. Anaemia is common in patients undergoing elective surgery; preoperative anaemia is detected in up to 40% of patients, with varying prevalence depending on the type of disease to be treated [
3‐
7]. Iron-deficiency anaemia (IDA) is the most common type of preoperative anaemia, accounting for nearly two-thirds of cases globally [
8]. Preoperative anaemia is associated with patients experiencing an increased length of hospital stay, a more complicated course of hospital treatment, an increase in the rate of blood transfusions, and higher mortality [
3,
9,
10]. A growing number of studies have shown that receiving a red blood cell concentrate (RBC) transfusion, often used to treat anaemia, is associated in a dose-dependent relationship with increased morbidity, mortality, and length of hospital stay [
11‐
17].
However, despite the known risks of anaemia and RBC transfusion, preoperative anaemia is still frequently ignored, with indiscriminate transfusion used as a ‘quick fix’. Munoz et al
. identified ten misconceptions that constitute serious barriers to the wider implementation of preoperative anaemia measures (PAMs) [
18]. Among these misconceptions were the following: preoperative anaemia may be caused by many conditions, some of which could be ameliorated or cured by the proposed surgery; preoperative anaemia poses no risk to patients, so scheduled procedures should not be delayed because of its presence; and the implementation of PAMs negatively impacts hospital personnel workload and is not cost-effective [
18]. It was concluded that these misconceptions should be immediately abandoned by healthcare providers and replaced by evidence-based strategies such as detection, diagnosis, and proper treatment of preoperative anaemia [
18].
The aim of this study was to estimate the potential clinical and health economic benefits of patient blood management (PBM) for patients undergoing elective surgery. A health economic model was developed to assess the impact of the implementation of one specific aspect of PBM, PAMs, in a large German population.
Patient Blood Management
PBM is a medical multidisciplinary approach to manage anaemia and is described in detail elsewhere [
19]. Briefly, PBM is a set of measures designed to minimise risk in the pre-, intra-, and post-operative setting. PBM seeks to achieve better patient outcomes by relying on the patient’s own blood rather than on donor blood via transfusion; it achieves this by focussing on optimising erythrocyte mass, minimising blood loss and bleeding, and optimising physiological reserves to improve quality of care [
16]. PBM is of critical importance for patients with anaemia or iron deficiency who are undergoing elective surgery, especially when they commonly exhibit a high probability of significant blood loss or transfusion [
4,
20]. PBM measures directly focus on reducing risk factors associated with anaemia, as these may have a negative effect on treatment outcomes. For patients undergoing elective surgery, this means that both morbidity and mortality risk can increase. A higher morbidity risk could mean, for example, exacerbation of a chronic disease and an overall longer hospital stay as a consequence. A higher risk of mortality may be the result of complications.
Preoperative Anaemia Measures
The benefits of PBM, including the implementation of PAMs (principally iron therapy), would be experienced by many stakeholders, most notably patients, hospitals, the outpatient sector, healthcare funding providers, and health policymakers. International and national guidelines recommend preoperative treatment of IDA and iron deficiency with iron as the standard of care [
4,
21‐
27]. PBM, including the use of PAMs and post-operative anaemia measures, have been shown to (1) shorten the length of hospital stay for patients undergoing emergency and elective surgery [
28], in patients having cardiac surgery [
29], major abdominal surgery [
30], elective surgery [
31], and hip and knee arthroplasty [
32]; (2) lower the rate of surgical complications [
28,
29,
31,
33]; (3) reduce mortality [
28]; (4) reduce post-operative readmissions [
32]; and (5) reduce the number of blood transfusions [
28,
30‐
35]. Moreover, the economic benefits of PBM, including the use of PAMs, have been shown to (1) significantly reduce direct hospital costs of RBC transfusions per patient [
36,
37]; (2) reduce overall hospital costs for patients undergoing hip and knee replacement surgery [
32,
38‐
40] and major abdominal surgery [
41]; (3) reduce costs to the healthcare system [
42,
43]; and (4) improve patient safety by reducing surgical complications and mortality [
28].
German Inpatient Healthcare System
In the system described in this study, the implementation of PBM incorporating PAMs would be organized and remunerated via the German Diagnosis-Related Groups (DRG) flat-rate system. The amount of DRG reimbursement depends on the type of illness (diagnosis), and the type and severity of operation required. Consequently, for patients with minor illnesses a smaller amount of remuneration is provided than for patients with serious illnesses who require more extensive treatment. The reimbursement per patient is calculated on the basis of an estimated range of length of hospital stay. Within this range, the same flat rate is paid regardless of the length of stay. For patients with a significantly longer or shorter length of stay, surcharges or discounts are paid on proof of medical necessity.
Preoperative treatment of a patient with iron deficiency (PAMs) prior to elective surgery is performed either at an outpatient practice (which refers the patient to hospital) or in a hospital outpatient clinic. In both cases, remuneration of PAMs is currently not regulated by the legislator in Germany, which suggests that there may be underuse of therapy in this area.
Discussion
This study demonstrates the epidemiological impact and economic costs to the German healthcare system of untreated preoperative IDA for patients undergoing elective surgery. Preoperative IDA is known to be associated with a range of risk factors, including increased likelihood of receiving a RBC transfusion [
4,
20]. Calculations based on representative hospital data suggest that a patient with IDA had a five-times higher risk of receiving a RBC transfusion during elective surgery than a patient without IDA. In addition, preoperative IDA and receiving a RBC transfusion were both associated with increased mortality and hospital costs.
The knowledge of the risks associated with preoperative IDA led to the exploration of PBM, and specifically PAMs, as a clinical approach to the management of preoperative anaemia in patients having elective surgery. To our knowledge, this is the first study to carry out a comprehensive model-based secondary data analysis with representative hospital data (DRGs) for an entire country to demonstrate the beneficial impact of the implementation of PAMs for patients with preoperative IDA, both in routine clinical practice and at a wider healthcare system level. It should be noted that the study by Froessler et al. [
30] already shows similar positive effects; however, that randomized clinical trial was based on a far smaller cohort and without specific DRGs.
The cost modelling used in this study shows that, for the population studied, the implementation of PAMs would help to ameliorate the impact of IDA for patients undergoing elective surgery. The positive benefits were most marked for the patient population with IDA and receiving a RBC transfusion, likely because these patients face the full array of heightened risks associated with both preoperative IDA and RBC transfusion. Because this population is the costliest to treat, the associated healthcare represents a substantial burden to the healthcare system; therefore, the introduction of a clinical management approach that would reduce this burden offers benefits to both the healthcare system and the patient. Other PBM measures to reduce patient risk, such as avoiding unnecessary blood loss during and after surgery and an economical RBC transfusion regimen, were not modelled when quantifying the cost savings. However, it is anticipated that the additional cost and benefit effects that could be achieved with those measures would be similarly impactful.
The results of this analysis demonstrate that the overall cost saving for the German healthcare system would be significant after the implementation of PAMs for patients undergoing elective surgery. For 2015, it was calculated that a net cost saving of €1029 million could have been made; equivalent to almost 1.58% of the total national hospital budget for Germany. This is the base case scenario; results of the sensitivity analysis suggest that when a maximum scenario is considered the saving could be as much as €2547 million (3.90% of hospital budget). The net cost saving includes lower direct and indirect costs. Lower direct costs from complication-free patient care result in lower direct treatment costs, such as lower personnel costs and less material used, e.g. RBC blood bags. Additional cost savings through saved treatment days and hospital capacity result in a reduction of the bed occupancy rate. This leads to a reallocation of hospital beds; fewer hospital beds can relieve burdens on health insurance funds and hospital staffing. It could therefore be considered that the implementation of PBM could provide reduced hospital direct treatment and indirect costs, while at the same time improving patient care. The analysis shows that direct and indirect cost savings are somewhat balanced (direct cost saving of €536 million, indirect cost saving of €503 million).
The findings of this study support the adoption of the best practice guidelines published by Munoz et al. [
4]. These statements include a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. When other specific population-based studies in the literature are considered, the findings from this study are in alignment. Calvet et al. conducted a study of 282 patients with colorectal cancer and anaemia, in which the cost impacts of three iron replacement strategies for reducing the use of RBC transfusion were assessed using cost-minimisation analyses. Intravenous ferric carboxymaltose therapy reduced hospital stay by 2.3 days compared with iron sucrose and by 2.6 days compared with oral iron therapy, resulting in cost savings of €485 and €274 per patient, respectively [
60]. In a comparative cost assessment of intravenous iron supplementation options (including blood transfusion) to the healthcare economy in the UK, it was concluded that blood, as a source of iron, is expensive and is the least attractive option from a cost perspective [
61]. Moreover, in a recent assessment of the cost benefits of PAMs in a German population, Froessler et al. reported that perioperative administration of PAMs resulted in hospital cost savings (€786 per case) based on reduced blood transfusions and length of stay after elective abdominal surgery [
62].
There are, however, some potential limitations to this study. First, it should be noted that the ICD coding of IDA is not optimised throughout the entire healthcare provision, starting in the doctor's surgery, and continuing in the hospital. In Germany, this is partly because laboratory tests for IDA are state-regulated in terms of quantity and price, and consequently a service provider may be exposed to negative economic incentives when conducting these tests. This is likely to lead to an underreporting of IDA in clinical practice and an observed event rate for IDA that is lower than that previously reported in the literature. In this study, the data are derived from a single country population; however, because the German healthcare system shares many commonalities with healthcare systems of other developed nations, the findings could be considered relevant beyond Germany. The results presented relate to the German healthcare system in 2015; more up-to-date data sets are now available, and it is conceivable that the existing analysis could also be applied to the German DRG Statistics 2016 and DRG Statistics 2017 to explore whether comparable results can be generated. The development of the model was based on a series of evidence-based assumptions derived from the literature; because these numerical assumptions were based on previous studies and somewhat limited data, it is possible that this could introduce a risk of inaccuracy in the subsequent calculations. In order to limit this risk, a univariate sensitivity analysis was conducted. With regard to confounding, on the basis of the data and analysis structure used, we were only able to depict any confounding, if there was any, through the selection of subgroups and grouping logics, but not through regression analyses or similar. Future analyses could incorporate this. It would be possible to carry out further analysis of the data set by age group; however, this was not conducted as such a reduction in the number of patients per group would result in an undesirable increase in the coefficients of variation.
It is a strength of our study that data were derived from a comprehensive and detailed large database including elective surgery of all types, in patients of all ages. In addition, all numerical assumptions that formed the basis of the model were averaged and generally considered conservative (e.g. in the calculation, 30% was selected as the proportion of preoperative patients with anaemia, whereas the range from the literature in fact spanned 20–40%), suggesting that the impact of implementing PAMs could in fact be much greater than that reported here. Sensitivity analysis allowed the range of impact of PAMs to be examined in more detail; this showed that the influence of an implementation of PAMs could be smaller, but also significantly larger than the base case suggests.
This large database analysis has shown that the implementation of PAMs for patients of all ages undergoing elective surgery would provide a host of benefits in terms of health economics, epidemiology, and favourable patient outcomes. It is hoped that these results will inform recommendations in the future on the management of patients having elective surgery.
Conclusions
The model developed in this analysis provides a simple method for calculating the impact of addressing IDA for preoperative patients undergoing elective surgery and illustrates the epidemiological and economic potential for implementing PAMs in a large population.
The impact estimates can be assessed at both patient and healthcare system levels. The model estimates show that a significant number of deaths, hospital treatments, and costly hospital days could have been avoided by the implementation of PAMs in Germany. On the basis of the calculations in this study for 2015, the potential cost savings of implementing PAMs were substantial, accounting for approximately 1.58% of the total annual hospital costs in Germany. The model described here could readily be adapted to other healthcare systems. Not only would the implementation of PAMs offer economic benefits at a national healthcare level, but the real health benefits to patients of reduced risk of receiving a blood transfusion are also evident.