Extract from the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery - Patient Blood Management

Abstract

The 2022 Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery of the European Society of Cardiology are an update on the previous guidelines reported in 2014. The revised guidelines provide standardized perioperative cardiovascular management of surgical patients and emphasis on risk assessment of the patient combined with the inherent risk of the surgical procedure. One of the novelties in these guidelines is the Patient Blood Management programme, which is based on a three pillar concept: preoperative hemoglobin optimization, minimize iatrogenic blood loss and bleeding, and harness tolerance to anemia in an effort to improve patient outcome. In this review, we highlight the three pillars of Patient Blood Management and recommendations made by the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.

INTRODUCTION

The guidelines of the European Society of Cardiology (ESC) represent the official position of the ESC on a given topic and are regularly updated. Guidelines summarize and evaluate available evidence, with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. The recommendations for formulating and grading of ESC guidelines can be found on the ESC website¹. The definition and wording of the recommendations and levels of evidence are depicted in Table I and II.

Table I.

Classes of recommendations

Table II.

Levels of evidence

Guidelines and their recommendations should facilitate decision-making of health professionals in their daily practice. These decisions are made in consultation with the patient and caregiver as appropriate. To ensure that all users have access to the most recent recommendations, the ESC makes their guidelines freely available.

The 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery² include for the first time a chapter on Patient Blood Management (PBM)^3,4. Since the publication of these guidelines, several landmark studies in the field of PBM have been published underlining the importance of this chapter. One example is the German PBM Network study of 1.2 million patients, showing that the implementation of PBM resulted in a substantial reduction of red blood cell (RBC) utilization among other benefits⁵. Similar observation was made in 9,635 patients undergoing total hip arthroplasty and total knee arthroplasty and 2,080 patients undergoing colorectal cancer surgery. PBM was associated with a substantial reduction of blood transfusion and hospital stay^6,7. In this paper, we present the recommendations from the 2022 ESC guidelines on PBM including management of pre-operative anemia, reduction of blood loss and indications for transfusion.

The members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. The selection procedure aimed to ensure a representative mix of members, predominantly from across the whole of the ESC region and from relevant ESC Subspecialty Communities. Consideration was given to diversity and inclusion, notably with respect to gender and country of origin.

A critical evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk-benefit ratio. The level of evidence and the strength of the recommendation of particular management options were weighed and scored according to pre-defined scales, as outlined below. The Task Force followed the ESC voting procedures. All recommendations subject to a vote achieved at least 75% among voting members.

The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conf licts of interest. Their declarations of interest were reviewed according to the ESC declaration of interest rules and can be found on the ESC website¹ and have been compiled in a report and simultaneously published in a supplementary document to the guidelines. This process ensures transparency and prevents potential biases in the development and review processes. Any changes in declarations of interest that arose during the writing period were notified to the ESC and updated. The Task Force received its entire financial support from the ESC without any involvement from the healthcare industry.

The ESC Clinical Practice Guidelines (CPG) Committee supervises and coordinates the preparation of new guidelines. The Committee is also responsible for the approval process of these guidelines. The ESC Guidelines undergo extensive review by the CPG Committee and external experts, including a mix of members from across the whole of the ESC region and from relevant ESC Subspecialty Communities and National Cardiac Societies. After appropriate revisions, the guidelines are signed-off by all the experts involved in the Task Force. The finalized document is signed-off by the CPG Committee for publication in the European Heart Journal. The guidelines are developed after careful consideration of the scientific and medical knowledge and the evidence available at the time of their writing. The task of developing the ESC Guidelines also includes creating educational tools and implementation programmes for the recommendations, including condensed pocket guideline versions, summary slides, summary cards for non-specialists, and an electronic version for digital applications (smartphones, etc.). These versions are abridged and thus, for more detailed information, the user should always access the full text version of the guidelines, which is freely available via the ESC website and the European Heart Journal.

The National Cardiac Societies of the ESC are encouraged to endorse, adopt, translate, and implement all ESC Guidelines. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably inf luenced by the thorough application of clinical recommendations. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, and in determining and implementing preventive, diagnostic, or therapeutic medical strategies. Nevertheless, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in considering each patient’s health condition and in consulting with that patient or the patient’s caregiver where appropriate and/or necessary. It is also the health professional’s responsibility to verify the rules and regulations applicable in each country to drugs and devices at the time of prescription and, where appropriate, to respect the ethical rules of their profession. Off-label use of medication may be presented in these guidelines if a sufficient level of evidence shows that it can be considered medically appropriate to a given condition and if patients could benefit from the recommended therapy. However, the final decisions concerning an individual patient must be made by the responsible health professional, giving special consideration to: (a) the specific situation of the patient. In this respect, it is specified that, unless otherwise provided for by national regulations, off-label use of medication should be limited to situations where it is in the patient’s interest to do so, with regard to the quality, safety, and efficacy of care, and only after the patient has been informed and provided consent; (b) and country-specific health regulations, indications by governmental drug regulatory agencies, and the ethical rules to which health professionals are subject, where applicable.

The definition and wording of the recommendations and levels of evidence are depicted in Table I and II.

PATIENT BLOOD MANAGEMENT

Major surgery is associated with a high risk of perioperative blood loss. Preferred treatment of acute anemia related to peri-operative blood loss is transfusion of allogenic blood products. However, a large body of evidence indicates that inappropriate transfusion of RBCs may be associated with inherent complications and impaired surgical outcome. Therefore, it is important to identify at-risk patients pre-operatively and manage peri-operative bleeding in any patients undergoing major surgery.

A hallmark study including >200,000 major surgical patients showed that even mild anemia significantly increased the risk of morbidity –including respiratory, urinary, wound, septic, and thromboembolic complications– and mortality across all age groups⁸. Moreover, Baron and colleagues analysed >39,000 surgical patients and showed that anemia was significantly associated with increased mortality rate, hospital length of stay, and postoperative admission to intensive care⁹. Up to 48% of surgical patients suffer from anemia, and therefore anemia should be considered to be a risk factor any time during hospitalization¹⁰. Von Heymann and colleagues analysed 4,494 cardiac surgical patients and showed that pre-operative anemia and intra-operative transfusion were independently associated with decreased long-term survival. In addition, long-term survival was decreased by 50% in anaemic patients receiving blood transfusion compared with those without blood transfusion¹¹ (Table III).

Table III.

Recommendations for intra- and post-operative complications associated with anemia

Recommendations	Class*	Level#
It is recommended to measure hemoglobin pre-operatively in patients scheduled for intermediate- to high-risk NCS 13,17	I	B
It is recommended to treat anemia in advance of NCS, in order to reduce the need for RBC transfusion during NCS 20,23	I	A
The use of an algorithm to diagnose and treat anaemic patients before NCS should be considered	II a	C

^*Class of recommendation.

^#Level of evidence.

NCS: non-cardiac surgery; RBC: red blood cell.

Anemia may contribute to myocardial ischemia, particularly if coronary artery disease (CAD) is present. Iron deficiency (ID) is the underlying cause of anemia in approximately 50% of all cases¹⁰. It was recently shown that ID was associated with increased risk of 90-day mortality both in patients with (4–14%) and without (2–5%) anemia¹². In addition, the incidence of serious adverse events, major cardiac and cerebrovascular events, allogenic blood transfusion requirements, and length of stay were increased in patients with ID.

Based on the possibility of preserving the patients’ own blood resources and to enable safe handling of donor blood, the World Health Assembly (WHA) has endorsed the Patient Blood Management (PBM) approach (WHA63.12). Patient Blood Management is a patientcentred and multidisciplinary approach to manage anemia (Table III and IV), minimize iatrogenic blood loss and bleeding (Table V), and harness tolerance to anemia in an effort to improve patient outcome (Table VI)^13–18. A comprehensive PBM programme addressing all three PBM pillars was associated with reduced transfusion need of RBC units, and lower complication and mortality rates¹³.

Table IV.

Laboratory parameters for the diagnosis of absolute iron-deficiency anemia

Parameter	Normal	Iron deficiency
Mean corpuscular hemoglobin (g/dL)	28–33	<27
Mean cellular volume (fL)	80–96	<80
Transferrin saturation (%)	16–45	<20
Ferritin (ng/mL)	18–360	<30*
Reticulocytes hemoglobin (ng/mL)	18–360	<30

^*In cases of chronic kidney disease, chronic heart failure or infections, iron deficiency is diagnosed with ferritin level <100 ng/mL or transferrin saturation <20%⁴¹.

Table V.

Recommendations for intra- and post-operative complications associated with blood loss

Recommendations	Class*	Level#
In patients undergoing surgery with expected blood loss of ≥500 mL, use of washed cell salvage is recommended37,42	I	A
It is recommended to use point-ofcare diagnostics for guidance of blood component therapy, when available31,43–47	I	A
In patients undergoing NCS and experiencing major bleeding, administration of tranexamic acid should be immediately considered35,36,48–50	IIa	A
Use of closed-loop arterial blood sampling systems should be considered to avoid blood loss27,42,51,52	IIa	B
Application of meticulous hemostasis should be considered a routine procedure13, 53	II a	B

^*Class of recommendation.

^#Level of evidence.

NCS: non-cardiac surgery.

Table VI.

Recommendations for intra- and post-operative complications associated with allogeneic blood transfusion

Recommendations	Class*	Level#
A feedback/monitoring programme or clinical decision support system should be considered to be assessed before blood transfusion40,54–57	IIa	B
Before allogenic blood transfusion, it should be considered to obtain an extensive consent about risks associated with transfusion	IIa	C

^*Class of recommendation.

^#Level of evidence.

PRE-OPERATIVE Anemia - DIAGNOSIS AND TREATMENT

A serum ferritin level <30 ng/mL, transferrin saturation <20%, and/or microcytic hypochromic red cells (mean corpuscular volume <80 fl, mean corpuscular hemoglobin <27 g/dL) are indicative of ID. In the presence of inf lammation or transferrin saturation <20%, a ferritin level of <100 ng/mL points to functional ID (iron sequestration) (Table IV).

Apart from compromised bone marrow function, most types of anemia are correctable within a period of 2–4 weeks. Oral and i.v. iron therapy can be used to treat ID. Intravenous iron products consist of an iron core embedded in a carbohydrate shell, which inf luences the stability of the drug, for example: iron sucrose comprises a less stable shell, allowing a maximum dose of 200 mg per infusion, whereas ferric carboxymaltose, ferric derisomaltose, and ferumoxytol have a stable shell associated with slow iron release and allowing a higher dose. Administration of i.v. iron has been shown to effectively reverse anemia in ID patients^19,20.

Intravenous iron is efficacious and safe²¹ and should be used in patients in whom oral iron is not tolerated, or if surgery is planned in short notice after the diagnosis of ID. A prospective observational study of 1,728 major surgical patients showed that the prevalence of ID was 50%, 46.3%, and 52.7% in patients with hemoglobin <8.0, 8.0–8.9, and 9.0–9.9 g/dL, respectively²⁰. Furthermore, all iron supplemented iron-deficient anaemic patients required fewer RBC transfusions during the post-operative period, and a reduced intra-operative transfusion rate was observed if iron was supplemented >7 days before surgery. In addition, the length of stay was significantly reduced by 2.8 days for iron supplemented patients.

In the recent PREVENTT trial studying patients with anemia undergoing major abdominal surgery, pre-operative iron transfusion failed to improve outcomes; however, due to the study design, all anaemic patients received i.v. iron but not all (~50–70%) were suffering from ID²². Therefore, an increase in hemoglobin level in non-iron-deficient patients treated with iron infusion is very unlikely.

Recombinant human erythropoietin (rHuEPO) has frequently been used together with iron supplementation to increase preoperative hemoglobin concentrations. A recent Cochrane review found that the administration of rHuEPO in combination with iron to anaemic patients prior to NCS, compared with control treatment, reduced the need for RBC transfusion and increased the hemoglobin concentration pre-operatively; however, there were no important differences in the risk of adverse events or mortality within 30 days, or in length of hospital stay²³. Well-designed, adequately powered RCTs are required to more precisely estimate the impact of this combined treatment.

Pre-operative management of patients with anemia can be simplified by making use of standard operating procedures or algorithms in which thresholds for diagnosis and treatment are depicted²⁴. An example of such an algorithm can be found in the PBM programme (Figure 1) and in the British Committee for Standards in Haematology (BCSH) Guidelines on the Identification and Management of Pre-Operative Anemia²⁵.

Figure 1.

Algorithm of the PBM programme

BLEEDING AND REDUCTION OF IATROGENIC DIAGNOSTIC/SURGERY-RELATED BLOOD LOSS

Blood loss associated with laboratory testing can either cause or aggravate hospital-acquired anemia, which is associated with increased length of stay and complications. In 1,867 patients undergoing cardiac surgery, an average of 115 tests per patient were performed, with a cumulative median volume of 454 mL²⁶. A reduction in blood drawn for laboratory analyses can be achieved by lowering the frequency of sampling and using paediatric-size collection tube sizes, for example. To decrease blood loss, blood-saving bundles could be used (e.g., a closed-loop arterial blood sampling system, smaller sampling tubes, reduction of frequency of blood drawings, and sample numbers). Such a strategy decreased mean blood loss per intensive care unit (ICU) day from 43.3 mL to 15.0 mL (p<0.001), mainly due to the introduction of closed-loop arterial blood sampling systems. In addition, units of transfused RBCs per 100 observation days decreased from 7 to 2.3 (p<0.001)²⁷ (Table V).

A reduction in surgery-related blood loss starts from the preoperative stage, with appropriate cessation strategies for anticoagulation and antiplatelet therapy. Intra-operative anesthetic approaches to avoid blood loss include: (i) advanced anaesthetic; (ii) advanced surgical techniques with meticulous hemostasis, such as minimally invasive surgery and laparoscopic surgery; (iii) judicious use of diathermy dissection; (iv) physician’s mindfulness regarding limiting blood loss; and (v) application of topical hemostatic agents^28–30 (Table V).

Adequate coagulation management to minimize blood loss needs to be a pre-condition before RBC transfusion is considered. In this respect, the use of a coagulation algorithm is recommended^31,32, encompassing pre-operative assessment, and ensuring basic conditions for hemostasis³², reversal of anticoagulants, point-of-care diagnostics in bleeding patients, and optimized coagulation management with the use of clotting factor concentrates^33,34 (Table V).

Tranexamic acid is an antifibrinolytic agent that is widely used for prophylaxis and treatment of bleeding caused by hyperfibrinolysis. A meta-analysis including 129 trials encompassing more than 10,000 patients to assess the effect of tranexamic acid on blood transfusion showed that administration of tranexamic acid reduced allogeneic blood transfusion by 38% (p<0.001)³⁵. In the recent POISE-3 study, 9,535 patients undergoing NCS were randomized to tranexamic acid (1 g i.v. bolus) or placebo at the start and end of surgery. The incidence of the primary efficacy outcome (composite bleeding outcome) at 30 days was significantly lower with tranexamic acid than with placebo (HR, 0.76; 95% CI, 0.67–0.87)³⁶. With respect to the primary safety outcome (composite CV outcome), the results did not meet the non-inferiority criteria (HR, 1.02; 95% CI, 0.92–1.14; p=0.04 for non-inferiority) (Table V).

The use of (washed) cell recovery is highly recommended in surgical settings where blood loss is routinely or anticipated to be >500 mL, as it reduces the rate of exposure to allogeneic RBCs, risk of infection, and length of stay. A meta-analysis including 47 trials encompassing 3,433 patients of all surgical disciplines showed that the use of washed cell salvage reduced the rate of exposure to allogeneic RBC transfusion by 39% (p<0.001), risk of infection by 28% (p=0.03), and length of stay by 2.31 days (p<0.001)³⁷ (Table V).

OPTIMAL BLOOD COMPONENT USE WITH PATIENT-CENTRED CLINICAL DECISION SUPPORT

In order to optimize utilization of allogeneic blood products and to ensure guideline-adherent transfusion strategies, computerized physician order-entry systems should be considered^38,39. For example, Kaserer and colleagues evaluated the effectiveness of a monitoring and feedback programme and compared transfusion rates of >210,000 patients before and after implementation; overall, transfusion of RBCs was reduced by 40%⁴⁰ (Table VI).

Informed consent should be obtained from patients prior to transfusion of allogeneic blood products. It is necessary to effectively communicate the risks and benefits of the various potential interventions to the patient. It may further be recommended that any transfusion of allogeneic blood products should be mentioned in the discharge summary. In addition, the patient’s own preferences and values should be considered when developing a medical plan.

CONCLUSIONS

It is well established, that the risk for postoperative complications is increased in patients undergoing major surgery with anemia compared to patients without anemia. Patient Blood Management is an evidence-based, multidisciplinary approach to manage and preserve patient’s own blood. To increase patient safety and ensure optimal medical care the ESC guideline recommend a preoperative anemia management in patients scheduled for intermediate- to high-risk NCS (Table IV). In addition, PBM offers strategies to minimise surgical blood loss (Table V) and evidence based transfusion strategies (Table VI).