Patient Blood Management: transfusion appropriateness in the post-operative period

Abstract

Background

Within the context of Patient Blood Management (PBM) policy for the peri-operative period, the transfusion medicine unit of our institution adopted a series of strategies to support and enhance red blood cell (RBC) transfusion best practices. This study aimed to evaluate the appropriateness of RBC transfusion therapy in the post-operative period, before and after starting a multifactorial PBM policy.

Materials and methods

A 2-phase observational study was conducted on patients who underwent major surgery. The study was designed as follows: 3 months of preliminary audit, followed by multifactorial PBM policy, and a final audit. The policy comprised seminars, teaching lessons, periodic consultations and the insertion of Points of Care. RBC transfusion appropriateness was evaluated in both audits.

Results

The preliminary audit, performed on 168 patients, showed that 37.7% of the patients were appropriately transfused. The final audit, performed on 205 patients, indicated a significant increase of RBC transfusion appropriateness to 65.4%.

Discussion

In our experience, our multifactorial PBM policy improved the RBC transfusion appropriateness in the post-operative period. We believe that our multifactorial PBM policy, which comprises the insertion of Points of Care, supported the healthcare workers in the transfusion decision-making process. This enhancement of transfusion appropriateness implies clinical and managerial advantages, such as reduced transfusion-related risks, optimisation of health care resources, and reduction in costs.

Introduction

Blood transfusion is a life-saving procedure in severe bleeding and life-threatening anaemia. However, the accepted benefits entail significant risks of morbidity and mortality, which include infection due to bacterial and viral contaminations, storage lesion of the blood units, and increased risk of immune-mediated adverse events^1–3. Over the last decade, attention has been directed toward achieving a consistent rise in quality, with the aim of improving the safety and efficacy of the transfusion therapy⁴.

Recent efforts aimed at promoting the proper use of blood components were converged into the multidisciplinary evidence-based approach called “patient blood management” (PBM)⁵, recognised by the World Health Organization as the new standard of care⁶. PBM strategies are directed toward optimising the cure of patients who might need blood transfusion by minimising the associated risks^4,5. However, there is still an over-use of red blood cells (RBC)⁷, which has led to the gap between supply and demand.

Patient blood management aims to optimise patient outcomes using techniques to minimise blood loss, avoid inappropriate blood usage with adequate preoperative evaluation, and an evidence-based use of blood and coagulation parameters. Moreover, it includes audits of physicians’ compliance using established transfusion criteria. These strategies should be developed during the pre-, intra-, and post-operative periods, and the involvement of all healthcare workers is essential to improve transfusion safety and appropriateness⁸.

Among PBM strategies, the introduction of continuous non-invasive Points of Care (POCs) could be of great advantage. The constant monitoring of the changes in patients’ haemoglobin (Hb) and other vital parameters gives real-time information on possible hidden bleeding and prevents the inappropriate use of allogeneic blood products in haemodynamically stable patients⁹.

In 2010, the Italian Society of Transfusion Medicine (SIMTI) published its recommendations for transfusion therapy in surgical patients during the peri-operative period^10–12, helping physicians decide on the appropriate use of blood products⁶. These endorsements were introduced in a Ministerial Decree on 2 November 2015¹³ and in the Ministerial Guidelines in January 2017¹⁴. The post-operative period usually presents a risk of developing anaemia due to hidden blood loss, reduced erythropoiesis, and repeated blood sampling^15,16. Severely ill patients with high levels of pro-inflammatory mediators^17,18 are more likely to develop post-operative anaemia. This study aimed to evaluate the adherence to SIMTI guidelines of RBC transfusion, in the post-operative period, before and after implementing the multifactorial PBM policy within a 2-year period.

Materials and methods

The study was carried out at the Scientific Institute for Research and Health Care (“Azienda USL-IRCCS”) of Reggio Emilia and was approved by the Ethical Committee of Reggio Emilia. Written consent and oral informed consent were obtained from all study participants according to the Declaration of Helsinki.

Study design

The study was conducted as follows (Figure 1):

Figure 1.

Timeline of the study.

PBM: patient blood management; POCs: continuous non-invasive Points of Care.

1. a preliminary audit (3 months) aimed at evaluating the appropriateness of RBC transfusion therapy after major surgery in three post-operative wards: semi-intensive post-operative (SIPO), post-surgery high-care unit (HC), and orthopaedic room (OR);

2. the multifactorial PBM policy consisted of a period of PBM training (3 months), followed by implementation of POCs for the continuous monitoring of Hb levels (12 months).

   PBM training included periodic seminars open to physicians and nurses of the post-operative wards concerning the applications of the SIMTI recommendations, and was arranged as follows:

   • - live teaching sessions;

   • - lectures by resident consultants and research fellows;

   • - periodical consultation with prescribers;

   • - POC training.

   Subsequently, specific POCs for the continuous, non-invasive monitoring of Hb levels (Radical-7 Pulse CO-Oximeter device; Masimo Corp., Irvine, CA, USA) were placed in each ward and used for 12 months. POCs were intentionally used in support, and not in replacement, of the routine analyses.

   The physician responsible for ordering RBC post operatively was the surgeon following the single patient, as established by our hospital plan. The transfusion medicine personnel did not interfere with the prescribers’ decisions.

   We are aware that there are factors that can influence accuracy of non-invasive Hb monitoring. However, besides having been validated in healthy subjects, POCs are used mainly in the intra-operative setting, where the prevalence of hypovolaemic/severely anaemic patients is particularly high, while in the post-operative setting, these confounding factors are more likely to be minimised. POCs, therefore, although not replacing the routine analyses, enter in an early phase of the transfusion decision process;

3. final audit regarding the appropriateness of transfusion therapy after PBM was conducted on patients monitored with POCs, who are those that benefit from the entire multifactorial PBM policy developed in our hospital. The assessment of transfusion appropriateness after a single phase of the programme (PBM training or after POC insertion) was beyond the aim of this study, since these two initiatives were intentionally undertaken together as part of the “Azienda USL-IRCCS” PBM. Final audit data collection and analysis lasted 3 months.

Patient population

The appropriateness of RBC transfusion was evaluated at the medical care unit of the “Azienda USL-IRCCS” on consecutive patients who underwent major surgery (in which an extensive resection was performed) and were subsequently admitted to SIPO, HC, and OR wards in the post-operative phase, which was defined as the period between the day after surgery and the day of discharge from the wards.

Patients’ demographic data and percentage of transfusions in the post-operative period are presented in Table I and Table II, respectively. Patients’ distribution based on the type of surgery is presented in Online Supplementary Tables SI and SII. The following clinical data were obtained from the hospital electronic database and electronic blood bank registry: diagnosis, comorbidities, surgical details, length of stay, Hb levels before surgery and at discharge. The following data were collected for each transfusion episode: 1) type of unit transfused; 2) patient’s demographic data; 3) diagnosis; 4) type of surgery; 5) comorbidities (i.e. cardiovascular diseases, pneumopathies, severe metabolic disorders, and debilitating chronic pathologies); 6) complications that occurred during surgery (i.e. infections, haemorrhage, and secondary surgery); 7) haematochemical exams (i.e. blood count and coagulation tests); and 8) current pharmacological therapies (i.e. anticoagulants, anti-hypertensives, and antibiotics).

Table I.

Distribution of the patients monitored within each audit.

	Preliminary audit	Final audit
Total n. of patients	168	205
Male	84	115
Female	84	90
Mean age (years)	68.7±14.7	69.1±15.7

Table II.

Distribution of transfused patients and number of red blood cell (RBC) units transfused.

	Preliminary audit	Final audit	p-value
Total n. of patients	168	205
Transfused with RBC units	53 (31.5%)	52 (25.3%)	p=0.187
Male transfused	23	28
Female transfused	30	24
Total RBC units transfused	170	119	*p=0.05

For both audits, patients affected by haematologic diseases were excluded from the evaluation of the appropriateness of RBC transfusions.

Appropriateness of red blood cell transfusion

The appropriateness of each transfusion episode was evaluated according to the SIMTI recommendations^10–12. Transfusions were considered appropriate based on the following conditions:

1. Hb under 80 g/L;

2. Hb 80–90 g/L only in the presence of risk factors (i.e. coronary pathology, cardiac insufficiency, and cerebrovascular pathology/limited compensation mechanisms);

3. Hb 90–100 g/L only in the presence of symptoms related to hypoxia (hypotension, electrocardiogram signal of ischaemia, and lactic acidosis).

Transfusions during the post-operative period were considered inappropriate in all other conditions.

Statistical analysis

Continuous data were expressed as mean±standard deviation (SD), and comparisons were made using an independent t-test. Categorical variables were described using frequencies and percentages, and analysed using a χ² test. For small size frequencies (<5), a Fisher’s exact test was performed. *p≤0.05 and **p≤0.01 were considered statistically significant. All analyses were performed using GraphPad Prism 7.02 software (GraphPad Software, San Diego, CA, USA).

Results

The preliminary audit was performed on 168 patients who underwent major surgery before starting a PBM policy. Next, a multifactorial PBM strategy was developed and applied as described in the Materials and methods section. The final audit was conducted on 205 patients monitored using POCs (Table II).

The patients transfused with RBC in the post-operative period were 31.5% (n=53) during the preliminary audit and 25.4% (n=52) in the final audit (Table II).

The number of RBC units transfused per patient decreased from 170 to 119 (30% decrease; p=0.05). During the preliminary audit, each of the 53 patients transfused with RBCs received 3.2±0.41 units, while the 52 patients transfused with RBCs in the final audit received 2.3±0.21 RBC units.

Pre-operative Hb levels were 12.6±3.8 and 11.9±4.0 for the preliminary and final audits, respectively. Hb levels at discharge were, however, 12.0±2.0 and 10.9±1.4.

Among the 53 patients transfused in the preliminary audit, 20 received an appropriate RBC transfusion (37.7%) based on the SIMTI recommendations (see Materials and methods for details). In the final audit, we observed a highly significant increase in RBC transfusion appropriateness (**p≤0.001), with 34 of 52 patients appropriately transfused (65.4%) (Figure 2).

Figure 2.

Percentage of patients who received an appropriate red blood cell transfusion in the preliminary and final audit.

**p≤0.001.

The appropriate transfusion events among the patients who received a single unit were 2 of 16 (12.5%) in the preliminary audit and 8 of 18 (44.4%) in the final audit. Transfusion appropriateness increased from 3 of 16 (23.1%) to 10 of 17 (58.8%) among the patients who received 2 units and from 15 of 24 (62.5%) to 16 of 17 (94.1%) among those transfused with 3 or more RBC units (Online Supplementary Figure 1S).

We also associated the RBC transfusion appropriateness with surgical timing, grouping the emergencies and the elective surgeries. In the preliminary audit, 10 of the 53 patients transfused with RBCs underwent emergency surgery and 43 underwent elective surgery, with transfusion appropriateness of 40.0% (4 of 10) and 37.2% (16 of 43), respectively. In the final audit, of the 52 patients transfused with RBCs, 7 underwent emergency surgery and 45 elective surgery, with appropriateness of 71.4% (5 of 7) and 64.4% (29 of 45), respectively.

After assessing the appropriateness of RBC transfusion according to SIMTI standards, we grouped the patients for the presence or absence of comorbidities (see Materials and methods for details). In the preliminary audit, 20 out of 53 patients transfused with RBCs had at least one comorbidity; among these, 14 received an appropriate RBC transfusion therapy (70.0%), and only 6 patients without comorbidities were appropriately transfused (18.2%).

In the final audit, 21 of the 52 patients transfused with RBCs were affected by at least one comorbidity: 15 were transfused appropriately (71.4%). Interestingly, among the 31 patients who were not affected by comorbidities, 19 (61.3%) received an appropriate transfusion (Figure 3).

Figure 3.

Appropriateness of RBC transfusion therapies in the presence/absence of comorbidities.

*p≤0.005.

Of note, we observed a decrease in the mean length of stay of transfused patients between the two audits, although this was not significant: 30±23 days vs. 25±20 days. Finally, we found no difference between the two audits in terms of 1-year mortality and re-hospitalisation for both transfused and non-transfused patients (data not shown).

Discussion

The lack of universally accepted indications on the correct use of haemocomponents often results in low transfusion appropriateness, especially in the post-operative period. This is caused by a high variability in the use of RBCs, plasma and platelets which does not usually correlate with the real clinical need and is attributable to the individual physician’s perception of the situation^19,20. This variability mainly affects patients belonging to the so-called “grey zone”, i.e., with Hb levels between 8 g/L and 10 g/L²¹, making it even more difficult to evaluate the appropriateness of the transfusion therapy.

To limit the indiscriminate use of haemocomponents, many transfusion medicine Societies worldwide, the SIMTI among them, have published their own recommendations^{10–12,22,23}. This study reported the results obtained by a 2-phase evaluation of the adherence to the SIMTI recommendations concerning the appropriateness of transfusion therapies carried out at the “Azienda USL-IRCCS” of Reggio Emilia in three post-operative wards: SIPO, HC, and OR.

To verify whether the multifactorial PBM strategy adopted could help to improve transfusion appropriateness, we compared the data between the preliminary and final audit.

We found a significant increase in RBC transfusion appropriateness, increasing from 37.7 to 65.4% of patients; this increase was independent of the number of units received by the patient in each transfusion episode.

The increase of transfusion appropriateness was accompanied by an overall reduction in the percentage of patients transfused with RBCs (from 31.5% in the preliminary audit to 25.3% in the final audit), as well as a statistically significant reduction in the total number of RBC units transfused (from 170 to 119; p≤0.05). This trend reflects a decrease in the units transfused per capita that passed from 3.2 to 2.3 mean RBC units received by each patient.

As far as the timing of surgery is concerned, encouraging results were observed for the elective surgery subset, for which we registered a significant increase in appropriateness as a possible consequence of our multifactorial PBM policy. Furthermore, we registered the highest significant increase in appropriateness for the subgroup of patients without comorbidities.

Although in our study we observed a general improvement in the post-operative use of RBC transfusion therapy, we found no difference on the 1-year mortality and re-hospitalisation outcomes between the two audits for both transfused and non-transfused patients. The hypothesis that RBC transfusions may affect clinical outcomes in a dose-dependent manner divides the scientific community. Some authors encourage a critical evaluation of the advantages and disadvantages of increasing Hb content in the individual patient, each of whom may face different (sometimes opposite) long-term outcomes²⁴. Future PBM studies should focus on a detailed identification of those sub-groups of patients who might benefit from RBC transfusions. Unfortunately, our study population is too small and heterogeneous to provide this.

However, taken together, we clearly demonstrate that the PBM strategies adopted by our hospital led to an improvement in the adherence to the SIMTI recommendations in the post-operative period. This is particularly true for those patients without comorbidities and in the elective surgery subset, for which the decision-making process is usually longer. These patients represented the majority of surgical admittances to our hospital, and their risk of receiving an inappropriate transfusion was higher than that of patients with severe anaemia with comorbidity who were admitted for emergency surgery.

The use of non-invasive POCs in the post-operative period (accompanied by an increased awareness of the importance of monitoring anaemia) might help physicians’ decision-making, especially in those cases in the “grey zone”, and for whom it might not be sufficient to simply provide prompt laboratory results.

Conclusions

We implemented a multifactorial PBM policy aimed at helping clinicians to make appropriate decisions concerning the transfusion therapy to be adopted. In our experience, this led to an increase in the appropriateness of RBC transfusion, which resulted in better management of the transfusion resources. Although our study did not assess the effect of PBM policy on different types of surgery, this is gaining interest in the scientific community and should be addressed across the entire peri-operative period. Indeed, surgical bleeding, together with the type of operation and Hb levels on admission to intensive care units, all play a key role in deciding the appropriate transfusion therapy. In the near future, we aim to investigate the appropriateness of blood transfusion by selecting specific patients who need particular care, taking into consideration the emerging risks associated with transfusion and the type of surgery.