Blood transfusion practice among medical physicians working at Kauno Klinikos Hospital

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1 Faculty of Medicine

Department of Intensive Care Sengin Lézan Zindrou

Blood transfusion practice among medical physicians working at Kauno

Klinikos Hospital

Medicine

Prof. Dr. Vidas Pilvinis Kaunas, Lituhania, 2017

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SUMMARY

Author: Sengin Lézan Zindrou

Title: Blood transfusion practice among medical physicians working at Kauno Klinkos Hospital. Aim: To review the clinical practice of blood transfusion in different clinical settings, to evaluate the threshold of blood transfusion as well as the units of blood used.

Objectives:

1. To assess blood transfusion threshold among physicians according clinical practice (different medical specialties).

2. To determine and compare the threshold for blood transfusion between younger physicians with less clinical practice and older physicians with more clinical practice in the intensive care department.

3. To evaluate current practice according present guidelines.

4. To determine if experience has any influence when it comes to blood transfusion.

Methodology: A scenario-based survey was conducted among 84 clinical physicians at the Lithuanian University of Health Sciences Kauno Klinikos. Distributing hypothetical scenarios and collecting data for hemoglobin trigger for each scenario estimated clinical practice of blood transfusion.

Study participants: Clinical physicians at the LUHS Kauno Klinikos.

Results: A total of 84 medical physicians, 33 (39%) of which were surgeons, 26 (31%) were intensivists and 25 (30%) of the physicians had different therapeutic specialties. The majority of the physicians in the first scenario, 38 (45,2%) chose a threshold of 80 g/L of hemoglobin. In the second scenario the majority 44 (52,4%) choose a threshold of 80 g/L, in the third scenario majority of the physicians 37 (44%) choose to transfuse at a threshold of 70 g/L and in the fourth and last scenario the majority which was 29 (34,5%) of the physicians choose to not plan a transfusion. There was no significant difference found between the groups of specialties (p>0,05)

Conclusions: Years of experience does not have an influence on the threshold chosen by clinical physicians working at Kauno Klinikos hospital, neither does the specialty of the physician. In general, the tactic was restrictive with some lack of knowledge in patients suffering with cardiovascular diseases receiving a transfusion.

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ACKNOWLEDGEMENTS

The author would like to thank the participated physicians for the help by filling the surveys, and Jurate Tomkeviciute who contributed in this research with statistical advices.

CONFLICT OF INTEREST

The author reports no conflicts of interest.

ETHICS COMMITTEE CLEARANCE

Title: Blood transfusion threshold among medical practitioners at Kauno Klinikos Hospital. Number of issue: BEC-MF-236

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ABBREVIATIONS LIST

1. Red blood cell (RBC) 2. Hemoglobin (Hb)

3. Transfusion Related Acute Lung Injury (TRALI) 4. Intensive Care Units (ICU)

5. Transfusion Requirements in Critical Care (TRICC) 6. Cardio Vascular Disease (CVD)

7. Hepatitis B (HVB) 8. Hepatitis C (HVC)

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INTRODUCTION

For many decades the decision to transfuse red blood cells was based up on a single criterion, perhaps the most well known rule in the history of blood transfusion, the so-called ”10/30 rule”. [1] However, in 1988 the National Institutes of Health Consensus Conference on Red Blood Cell Transfusions suggested that the indication for red blood cell transfusion should not be based on one single criterion, and that other factor such as the clinical and oxygen status of the patient should be taken in consideration. [2] Nonetheless, until today there is still an ongoing discussion regarding red blood cell transfusion and its indications. Perhaps due to the fact that our knowledge about physiology of anemia, ischemia and oxygen transport is improving, and also the methods used to assess appropriate physiological parameter is becoming more accessible in clinical practice, these indications are being modified with time. [3] In addition, blood transfusion includes several risks such as transfusion-related acute lung injury, infectious complications, ABO- and non-ABO-associated hemolytic transfusion reactions, associated Graft-versus-Host disease, and transfusion-associated circulatory overload. [4] Since these complications are transfusion-associated with increased morbidity and mortality of the transfused patient, questions regarding risks versus benefits have been raised, as well as when it is most appropriate to perform a red blood cell transfusion. These questions are constantly being challenged in current clinical practice [1]. In the last 25 years a large amount of clinical evidence have been generated, resulting in several articles being published about guidelines on indications for transfusion in different clinical settings with the goal to improve the practice and guide physicians to use transfusions only for appropriate cases. [5-10] However, the clinical practice today varies and the outcomes still differs. [11]

This leads us to the question whether to transfuse or not in different clinical settings, and it makes it interesting to know the practice among physicians today after the publication of these guidelines. A study performed using a scenario-based survey, physicians were given hypothetical scenarios and asked to choose the appropriate hemoglobin level for which they would decide to perform a RBC transfusion, was distributed among physicians in Canada. That particular study has been the ruler of the study carried out at Lithuanian University of Health Sciences Kauno Klinikos, with the aim to investigate the practice of blood transfusion, more specifically the threshold of hemoglobin level and units of blood among clinical physicians with different medical specialties (surgeons, intensivists and other therapeutical specialties) and to evaluate if years of experience has any influence on when to performed blood cell (RBC) transfusion. Distributing a modified version of the scenario-based survey collected the data in this study.

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AIM AND OBJECTIVES OF THE THESIS

Aim: To assess the use of blood transfusion, its thresholds and the units used in clinical practice and to evaluate the current practice according present guidelines.

Objectives:

1. To assess blood transfusion threshold among physicians according clinical practice (different medical specialties).

2. To determine and compare the threshold for blood transfusion between younger physicians with less clinical practice and older physicians with more clinical practice in the intensive care department.

3. To evaluate current practice according present guidelines.

4. To determine if experience has any influence when it comes to blood transfusion.

LITERATURE REVIEW

Anemia. The definition of anemia is questionable and it may vary with different factors such as the sex, age, and ethnicity of every patient. [12] However, according the World Health organization (WHO) anemia is defined when the hemoblogin are at a level less than 130 g/L in men, and less than 120 g/L in women, and in severe cases less than 80 g/L. [12-13] In a study performed it was shown that the prevalence of anemia in patients hospitalized in the intensive care unit (ICU) range from 60-66% at admission, and up to 90%, and 97% at the 3rd and 8th day respectively. [12] Anemia is stated to be one of the most common reasons for receiving a red blood transfusion among critically ill patients [14] and the etiology for this may be single or multifactorial [12], in hospitalized patients the different causes for anemia may include iron deficiency, suppression of erythropoietin and iron transport, trauma, coagulopathies, adverse effects of and reactions to medications, and gastrointestinal blood loss. [12] Additional reasons in the intensive care unit may be numerous bloods sampling for clinical evaluation purposes. [15] Even though iron deficiency may affect a large number of critically ill patients, nutritional insufficiency may also contribute to the loss of iron, including B12 and folate deficiency, all leading to anemia through unsuccessful eryhtropoiesis. [12, 14] This is explained by the fact that normally in a healthy patient there is a direct correlation between hemoglobin level and the concentration of erythropoietin, which is a hormone, synthesized in the kidneys as a response to deprivated oxygen levels in tissues that stimulate the erythroid progenitor cells to form red blood cells

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9 (RBC) in the bone marrow. And when there is low oxygen tension in tissues due to decreased hemoglobin concentration, the levels of erythropoietin is increased leading to the increased production of RBC (process called eryhtropoesis). In case iron stores in the body are depleted due to nutritional deficiencies, the production of hemoglobin is impaired leading to production of smaller and less RBC containing a decreased level of hemoglobin. [12]

When anemia occurs the body responses through different physiological mechanisms, as an attempt to compensate for the decreased levels of hemoglobin. These mechanisms include increased cardiac output, increased coronary artery blood flow, increased oxygen extraction, redistribution of blood flow and an increase of red blood cell 2,3-diphosphoglycerate. [16] If various clinical factors are present such as coronary artery disease, disorders of the heart valve or acute respiratory distress syndrome, the compensatory mechanism may be affected. [16]

In case of anemia, the purpose when using blood transfusion as a treatment, are usually to increase the arterial oxygen and thus to increase andmaintain the oxygen delivery to the organs and tissues. [(17-18] However, in patients were there is no indication for an urgent blood transfusion but a need to correct the anemia, other alternatives are favored such as folic acid, iron, recombinant erythropoietin and vitamin B12 (haematopoetic drugs) as treatment. [16]

Blood transfusion. The process of blood transfusions involves transferring blood or blood products intravenously, from a donor to a recipient. Transfusions are used in different medical conditions with the aim to replace the lost components of blood. In early years, blood transfusion included the transfusion of whole blood, but in current medical practice it is possible to transfuse separate components of blood, such as red blood cells, white blood cells, plasma, clotting factors and platelets. [19]

Indications. The main indications for blood transfusion include cases of anemia and hemorrhage. Red blood cell transfusion is used to treat hemorrhage when there is a loss of 1500 mL or 30% of total blood volume, and to increase the oxygen supply to the tissues in the body when physiological mechanisms fail to compensate the reduced hemoglobin level and the decreased oxygen carrying capability. [16, 20] In addition to this, initiating a blood transfusion should not only be based on parameters such as hemoglobin and hematocrit levels, but should also include evaluating the overall condition and clinical state of the patient. [11, 16]

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10 Practice. Transfusing red blood cells or another blood product is a common procedure in the intensive care unit (ICU). It is stated that approximately 30-50% of the patients in the ICU, depending on the case, receive a red blood cell transfusion. And on a national scale, 10% out of all the RBCs transfusion is performed in the ICU and studies have shown that the greater part is given for patients with anemia and that 20% are given to treat hemorrhage cases. [13] Historically, the trigger for blood transfusion was based on the ”10/30 rule” for many years, indicating that a hemoglobin level of 100g/L and hematocrit of 30% should be maintained in surgical patients, but was also later on implemented in other clinical settings, one of them being the intensive care unit. [3] However, after the publication of Transfusion Requirements in Critical Care (TRICC) the strategies of blood transfusion trigger changed into a more restrictive one. [3, 21] The reasons why this study was conducted includes the risks and complications critically ill patients were facing when receiving a red blood cell transfusion, to evaluate anemia tolerance in critically ill, and also the safety and supply of transfusions was a concern. [21] The idea was to conclude if using a restrictive strategy would give the same results, in terms of outcome and benefit as using a liberal strategy, and hopefully decrease the numbers of transfusions and thus decrease the risks of complications patients are facing with each transfusion. So, in 1999 the “Transfusion Requirements in Critical Care” (TRICC) study carried out a random trial to evaluate the possible benefits of a restrictive vs. liberal threshold of hemoglobin (Hb) level for blood transfusion among critically ill patients. [21] Out of 838 patients that were included in this study, 418 of them received a restrictive approach of blood transfusion (transfusion was given when Hb concentration had a value below 70g per liter, and Hb concentrations were maintained between 70 to 90g per liter), and 420 received a liberal approach (transfusion was given when Hb concentration had a value below 100g per liter, and Hb concentrations were maintained between 100g to 120g per liter). The result of the study was that a threshold of 70 g/L of hemoglobin (restrictive tactic) was no less effective than a threshold of 100g/L hemoglobin (liberal transfusion tactic) and that there was no difference in all-cause-30-day mortality in neither of the groups (18.7 percent vs. 23.3 percent, P= 0.11). It was also stated that the range of hemoglobin maintenance could be at a level of 70 g/L to 90 g/L compared to before, which was an Hb level of 100 g/L to 120 g/L. This did in turn mean that in the group of patients receiving a restrictive transfusion tactic, the number of red blood cell units transfused was decreased by 54% and the numbers of transfused patients also decreased by 33%. In the liberal group all of the patients were transfused. [13, 21]

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11 Many years has passed since the study about Transfusion Requirements in Critical Care trial was published and a number of researches have showed to reduce their number of transfusions. [3] In a retrospective study about changes in clinical practice of RBC transfusion it was concluded that the patients undergoing abdominal aortic aneurysm (AAA) surgery between the years of 2003-2006 had a decreased number of RBC transfusions and a lesser preoperative hemoglobin level, in comparison to the patients undergoing the same type of surgery between the years of 1980-1982. [22] In another study published in 2005, the aim was to observe the changes in blood transfusion practice over time among Canadian critical care practitioners (using a scenario based survey), it was concluded that 85% of the Canadian physicians had changed their tactics since the publication of the TRICC clinical trial in Canada. Their adopted approach included having a lower transfusion trigger and an increase use of single-unit red blood cell transfusion (results showed an increase of 56% choosing a single unit in 2002 vs. 10% in 1993). [23] However, more recent studies show that there is still a variation in the practice of blood transfusion in different settings. One study showing this is the CRIT study performed in the United States. In a total of 284s ICUs in 213 hospitals, it was concluded that practice of blood transfusion has changed little over time. The incidence of anemia is high and most likely results in blood transfusion as treatment. It was also concluded that increased mortality, longer ICU and hospital lengths of stay was related to the amounts of RBC transfusions a patient received during the course of the study. Also patients that were receiving a transfusion had an increased incidence of a complication. [3]

Another important issue to keep in mind is that the practice of blood transfusion may vary in different clinical settings, it may include clinical practice among trauma patients, bleeding patients (eg, GI bleeding), septic shock patients and anemia in patients with cardiovascular diseases (CVD) and many other scenarios likely to need a red blood cell transfusion.

In a study about “red blood cell transfusion in adult trauma and critical care” from 2010, a clinical practice guideline was developed for this particular setting. Their results included recommendations for critically ill trauma patients and stated that an Hb level of 70 g/L is safe to use, also that there is no benefit of using a liberal tactic (Hb transfusion trigger at 100 g/L) in a resuscitated critically ill trauma patient. [26] In another retrospective study, with the focus on trauma patients in the ICU and current transfusion practice, it was concluded a large amount of transfusions is performed among adult trauma patients and that the restrictive tactic of transfusion was safe to use and that critically ill trauma patients stand quite low levels of Hb. [24]

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12 In a different clinical setting, a study from 2017, with patients suffering from cardiovascular diseases receiving blood transfusion, concluded that there is a low quality of evidence to support a proper transfusion trigger to be used. However, this study states that 30% of patients admitted to the ICU in the United Kingdom have co-existing CVD and that is it an increasing number due to age of population and number of admissions to the ICU increase. When anemia occurs in a healthy patient the body responds through different compensating mechanisms, however in patients with CVD this compensatory mechanism will be impaired and will not be able to properly delivery oxygen to all the tissues in the body. This in turn will increase the work of the heart causing it to increase in cardiac output (CO), heart rate and stroke volume further stressing the heart and eventually may lead to a decreased heart supply through the coronary arteries, leading to ischemia to the heart. The meta-analysis and systematic review evidence in this study demonstrated that there were no difference in a 30-day mortality between groups of restrictive transfusion patients compared with a more liberal group, however the risk of acute coronary syndrome did increase. So there may be a chance that patients with CVD and anemia would benefit from a more liberal approach of RBC transfusion, a threshold of >80 g/l was recommended. [25]

Guidelines. Guidelines for blood transfusion have been published in many different setting [5-10] examples including the American Society of Anesthesiologists, [5] the British Committee for Standards in Hematology [6], the American Association of Blood Banks [7], the American College of Physicians [8] the Society of Critical Care Medicine [9] and the European Society of Cardiology [10], all with the similar recommendation that a more restrictive approach, a threshold of 70-80 g/L, should be applied in various clinical settings. However, not all cases are the same and there is a special need of caution when observing or identifying a decrease in Hb concentration level in some patients, such cases may include patients suffering from CVD, expressed symptoms of anemia, continuous bleeding or patients with a traumatic brain injury. In those cases the Hb threshold is recommended to be at a level of 80-100 g/L. [11]

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13 Complications of blood transfusion. In terms of history, the most common types of viral complications included the transfer of hepatitis B (HVB), hepatitis C (HVC) and human immunodeficiency virus (HIV), which over the past two decades has decreased significantly. This improvement is a result of a combination between improved screenings of blood products as well as a limiting donor selection. [26] In a study performed in England, with the aim to evaluate the risks of infectious donations entering the blood supply between years of 1993 to 2001, the results showed that the risk was very low in concern of infectious donations, and have declined since 1993. During the period of 1993 to 2001 the frequency for infectious donations was 1 in 260,000 for HBV and 1 in 8 million for HIV. The frequency for HVC was 1 in 520,000 between the periods of 1993 to 1998, and later decreased drastically to 1 in 30 million between the years of 1999 to 2001. [27] A similar study was performed in Italy which included close to 90% of the total blood supply; their results also showed that the risk of infectious donations was low, especially HIV infections was lower than the risk of HCV or HBV. [28] Although these studies may show good results there are still some countries that do not have the same possibilities to select and manage blood from donor and thus do not have the same results. In Nigeria for example, the second most common cause of HIV is through blood transfusion. [29] On the other hand, even though blood transfusion may be seen as a procedure that may save lives, it still includes many risks and complications, for instance, transfusion-related acute lung injury (TRALI) is yet one of the leading complications after an blood transfusion. Also transfusion associated Graft-Versus-Host disease, transfusion-associated circulatory overload, ABO- and non-ABO-associated hemolytic transfusion reaction and are complications that may be seen in practice. [4, 30] TRALI is a clinical syndrome that is seen in 6 hours after a blood transfusion. According to a study performed in 2012, it was stated that risk factors for TRALI included receiving blood products from female donors and that reducing transfusion from female donors would in turn decrease the incidence of TRALI. [30] With this said, blood transfusions comes with a high risk of complications and therefore it is necessary to evaluate benefits vs. possible clinical outcomes before choosing to transfuse.

In addition to this, due to these various complications many randomized controlled clinical trials have taken part of the research world to evaluate and compare the morbidity and mortality of blood transfusion in patients with a restrictive transfusion tactic and a liberal transfusion tactic. [4] In a systematic review from 2016, 31 trials and 12,587 participants were included in a study with the aim to compare the restrictive and liberal transfusion tactic and its impact on a 30-day morbidity and mortality.

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14 It was concluded that a restrictive vs. liberal transfusion tactic showed no evidence in difference in an all-cause-30-day morbidity or mortality. It was also concluded that in this distinct study using a restrictive tactic decreased the chances of receiving a red blood cell transfusion by 43% in a wide range of clinical specialties. [31]

RESEARCH METHODOLOGY AND METHODS

Study population and administration. This study was conducted in Lithuanian University of Health Sciences (LUHS) Kauno Klinikos using an anonymous scenario based survey. The scenarios were self-administered to the clinical physicians at the Kauno Klinikos hospital between December 2016 and January 2017. After the approval of their participation a description of the study was provided, and they were asked to follow the instructions written on the survey and fill in the asked physician characteristics. The object of the study included the physicians working as surgeons, intesivists or working as other therapeutics (different specialties). The collected data was divided into three separate groups according these distinct specialties. In total 84 physicians participated in this study. It was conducted on 33 physicians working as general surgeons, and included 12 physicians with more years clinical experience in practice and 21 younger physicians with less clinical experience, and 26 physicians from the intensive care unit, which included 10 physicians with more clinical experience and 16 physicians with less clinical experience. The group of physicians with different therapeutic specialties was in total 25 physicians, and only 3 of them were physicians with more clinical experience and the remaining was younger physicians. The physicians with different therapeutic specialties included gastroenterologist, pulmonologist, dermatologist, cardiologists and internals. The distribution and collection of data was done separately in each department with personal sessions. It was made clear that their contribution to this research would not affect their medical position. Each survey took about 10-15 min to fill in and was collected the same day, after completing filling.

Survey development and scenario description. Experts and an interative process among investigators developed a scenario based survey used in a Canadian blood transfusion threshold article. [23] The scenarios in t study was modified from the one used in the Canadian survey and the final version of the survey was composed of four scenarios, two surgical and two therapeutic cases. The therapeutic scenarios illustrated a patient with gastrointestinal hemorrhage and a patient with severe community-acquired pneumonia with suspicion of severe sepsis. The surgical scenarios described a multiple trauma patient and a patient with postoperative myocardial infarction. The scenarios provided

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15 included the age, gender, clinical status, hemodynamic state and the presence or absence of hypoxia of the different hypothetical cases, that could be seen as a trigger to transfuse or not. The hemoglobin concentration threshold was recorded by giving five distinct options (60 g/L, 70 g/L,80 g/L, 90 g/L, >100 g/L). A modification was made in the last scenario adding a sixth option for recording the blood transfusion threshold: “I would not plan a transfusion”. The survey also recorded information about the physicians participating in this study, their medical specialties, and years of experience and if they were working as residents or senior physicians.

Statistical analysis.

Data were analyzed using IBM SPSS statistics version 23.0 (IBM Corporation, New York, USA). The qualitative data is presented in frequency (n) and percentages (%). Comparing qualitative data in groups (different medical specialties), Chi-square test was used and significant difference was found when statistical significance p<0,05.

RESULTS

Physician characteristics

A total of 84 physicians responded to the survey distributed at Lithuanian University of Health Sciences (LUHS) Kauno Klinikos, 33 (39%) of which were surgeons, 26 (31%) were intensivists and 25 (30%) of the physicians had different therapeutic specialties. The average number of years of clinical practice among the intensive care physicians was 11 (12, 3) years, among the surgeons the average was 8 (10, 7) years and in the group of other therapeutic specialties the clinical practice was about 4 (5, 1) years. The total average of years of clinical practice including all physicians in this study was 8 (10,4) years.

RESULTS OF THE MOST COMMON TRANSFUSION TRIGGER IN ALL SCENARIOS AMONG ALL PHYSICIANS

The majority of the physicians in the first scenario, 38 (45,2%) choose a threshold of 80 g/L of hemoglobin, 33 (39,3%) choose to transfuse at 70 g/L, 7 (8,3%) choose to transfuse at 90 g/L, 5 (6%) choose to transfuse at 60 g/L and 1 (1,2%) choose to transfuse at ≥100 g/L. No one choose to ’’not plan a transfusion” since it was not an option in this scenario.

In the second scenario the majority of the physicians, 44 (52,4%) choose a threshold of 80 g/L, 33 (39,3%) choose to transfuse at 70 g/L, 5 (6%) choose to transfuse at 90 g/L, 1 (1,2%) choose ≥100 g/L

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16 and 1 (1,2%) choose 60 g/L. No one choose to ’’not plan a transfusion” since it was not an option in this case.

In the third scenario, the majority of the physicians 37 (44%) choose to transfuse at a threshold of 70 g/L, 30 (35,7%) choose to transfuse at the level of 80 g/L, 10 (11,9%) choose 60 g/L, 4 (4,8%) choose 90 g/L and 3 (3,6%) choose to transfuse when the hemoglobin level was ≥100 g/L. No one choose to ’’not plan a transfusion” since it was not an option in this case.

In the fourth scenariothe majority, 29 (34,5%) of the physicianschoose to not plan a blood transfusion. 23 (27,4%) choose 80 g/L as a hemoglobin threshold, 19 (22,6%) choose 90 g/L, 10 (11,9%) choose 70 g/L, 2 (2,4%) choose ≥100 g/L and 1 (1,2%) choose to transfuse at the level of 60 g/L.

Figure 2. Blood transfusion trigger among all physicians in every scenario summarized in one table

* There was no significant difference found between the most common transfusion trigger among all physicians p > 0,05 5(6%) 33(39,3%) 38(45,2%) 7(8,3%) 1(1,2%) 1(1,2%) 33(39,3%) 44(52,4%) 5(6%) 1(1,2%) 10(11,9%) 37(44%) 30(35,7%) 4(4,8%) 3(3,6%) 1(1,2%) 10(11,9%) 23(27,4%) 19(22,6%) 2(2,4%) 29(34,5%) 0 10 20 30 40 50 60 60 g‎/L 70 g‎/L 80 g‎/L 90 g‎/L ≥100 g‎/L I wouldn't plan a transfusion Scenario 1 Scenario 2 Scenario 3 Scenario 4

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17 RESULTS OF THE MOST COMMON TRANSFUSION TRIGGER AND UNITS USED IN

EACH SCENARIO Scenario 1 – Hemoglobin threshold

- Describes a patient after poly-trauma admitted to the ICU (surgical case).

In the first scenario the majority of the intesivists, 13 (50%), choose to transfuse at the level of 80 g/L, 9 (34,6%) choose 70 g/L, 2 (7.7%) choose 60 g/L and 2 (7.7%) choose 90 g/L, whereas no physician choose to transfuse at the level of ≥100 g/L in this group.

The majority of the surgeons, 16 (48,5%), choose to transfuse at the levels of 70g/L, 13 (39,4%) choose 80g/L, 2 (6,1%) choose 90g/L and2 (6, 1%) choose 60 g/L, whereas no physicians choose to transfuse at the level of ≥100 g/L in this group.

In the group of other therapeutic specialties, the majority of the physicians 12(48%) choose to transfuse at the level 80g/L of hemoglobin, 8 (32%) choose 70 g/L, 3 (12%) choose 90g/L, 1 (4%) choose ≥100, and 1 (4%) choose to transfuse at 60g/L.

Figure 3: Hemoglobin threshold for scenario 1, demonstrating different between groups of specialties

* There was no significant difference between all specialties in choosing RBC transfusion threshold for scenario 1. p>0,05 2(7,7%) 9(34,6%) 13(50%) 2(7,7%) 2(6,1%) 16(48,5%) 13(39,4%) 2(6,1%) 1(4%) 8(32%) 12(48%) 3(12%) 1(4%) 0 10 20 30 40 50 60 60 g‎/L 70 g‎/L 80 g‎/L 90 g‎/L ≥100 g‎/L ICU Surgery Other therapeutic specialities

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18 Scenario 1 – Corresponding units

- The respondents were supposed to choose units given to the corresponding scenario after choosing threshold for blood transfusion.

In the group of intensives, the majority 23 (88,5%), choose to transfuse 2 units of blood in this particular scenario, 3 (11,5%) choose 1 unit whereas no physician choose to give 3 or 4 (or more) units for transfusion.

In the group of surgeons the majority of them, 29 (87,9%) choose to give 2 units, 4 (12,1%) choose 3 units, whereas no physician among the surgeons choose to give only 1 unit or4 (or more) units.

In the therapeutic group, the majority of the physicians 22 (88%), choose to give 2 units of blood, 2 (8%) choose to give 3 units and 1 (4%) physician choose to give 1 unit. No physicians choose to give 4 units or more.

Figure 4: Units chosen for patient in hypothetical scenario 1

* There was no significant difference between all specialties in choosing units for hypothetical patient in scenario 1. p>0,05 3(11,5%) 23(88,5%) 29(87,9%) 4(12,1%) 1(4%) 22(88%) 2(8%) 0 10 20 30 40 50 60 70 80 90 100

1 unit 2 units 3 units

ICU Surgery

Other therapeutic specialities

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19 Scenario 2 - Hemoglobin threshold

- Described a patient with gastrointestinal hemorrhage admitted to the ICU (therapeutic case).

In the second scenario, the majority of the intesivists which was 13 (50%) of the physicians in this group choose a threshold level of 80g/L, 10 (38,5%) choose 70g/L, 2 (7, 7%) choose 90 g/L, and 1 (3,8%) choose 60 g/L. No intensivists choose to transfuse at a level of ≥ 100 g/L.

The majority, 18 (54,5%) of the surgeons choose to transfuse at the levels of 70g/L, 14 (42,4%) choose 80g/L, and 1 (3%) choose 90 g/L. No physicians in this group choose a hemoglobin threshold of 60 g/L or at a level of ≥ 100 g/L as an indication for blood transfusion in this scenario.

In the group of other therapeutic specialties, the majority of the physicians 17 (68%) choose to transfuse at 80g/L, 5 (20%) choose 70 g/L, 2 (8%) choose 90g/L and 1 (4%) choose 100 g/L, whereas no one choose 60 g/L.

Figure 5: Hemoglobin threshold for scenario 2, demonstrating different results between groups of specialties

* There was no significant difference between all specialties in choosing RBC transfusion threshold for scenario 2. p>0,05 1(3,8%) 10(38,5%) 13(50%) 2(7,7%) 18(54,5%) 14(42,4%) 1(3%) 5(20%) 17(68%) 2(8%) 1(4%) 0 10 20 30 40 50 60 70 80 60 g/L 70 g‎/L 80 g‎/L 90 g/L ≥100 g‎/L ICU Surgery Other therapeutic specialities

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20 Scenario 2 –Corresponding units

The majority of the intensivists, 21 (80,8%) choose to give 2 units of blood, 2 (7, 7%) choose 1 unit and 2 (7,7%) choose to give 4 units or more, whereas 1 (3, 8%) chooses to give 3 units of blood.

Surgeons majority of choice, 22 (66,7%) was to transfuse 2 units of blood, 7 (21,2%) choose 3 units,3 (9,1%) choose to transfuse 1 unit of blood and 1 (3%) choose to give 4 or more units of blood.

In the group of therapeutics the majority, 22 (88%), choose to give 2 units of blood, 2 (8%) physicians choose 3 units and 1 (4%) choose to give 1 unit of blood, and no one in this group choose to give 4 or more units of blood.

Figure 6: Units chosen for patient in hypothetical scenario 2

* There was no significant difference between all specialties in choosing units for hypothetical patient in scenario 2. p>0,05 2(7,7%) 21(80,8%) 1(3,8%) _2(7,7%) 3(9,1%) 22(66,7%) 7(21,2%) 1(3%) 1(4%) 22(88%) 2(8%) 0 10 20 30 40 50 60 70 80 90 100

1 unit 2 units 3 units 4 units or

more

ICU Surgery

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21 Scenario 3 - Hemoglobin threshold

- Described a patient with community-acquired pneumonia admitted to the ICU (therapeutic case).

In the third scenario the majority of the intensivists, 14 (53,8%), choose to transfuse at a level of 70g/L, 8 (30,8%) choose 80g/L and 4 (15,4%) choose 60 g/L whereas no physician choose to transfuse at either 90 g/L or ≥100 g/L.

The majority of the surgeons, 12 (36,4%), choose to transfuse at the levels of 70 g/L, 11 (33,3%) choose 80g/L, 6 (18,2%) choose 60g/L, 3 (9,1%) choose ≥100 g/L and 1 (3%) choose 90g/L.

In the group of other therapeutic specialties, the majorities choose to transfuse at level of 70 g/L and 80 g/L, out of which 11 (44%) choose 70 g/L and also 11 (44%) choose 80g/L of hemoglobin. 3 (12%) of the physicians choose 90 g/L. No one choose to transfuse at 60g/L or at ≥100 g/L.

* There was no significant difference between all specialties in choosing RBC transfusion threshold for scenario 3. p>0,05 4(15,4%) 14(53,8%) 8(30,8%) 6(18,2%) 12(36,4%) 11(33,3%) 1(3%) 3(9,1%) 11(44%) 11(44%) 3(12%) 0 10 20 30 40 50 60 60 g/L 70 g‎/L 80 g‎/L 90 g‎/L ≥100 g‎/L ICU Surgery Other therapeutic specialities

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22 Scenario 3– Corresponding units

Among the intensivists the majority of physicians, 18 (69,2%), choose to transfuse 2 units of blood and 8 (30, 8%). No one choose to give 3 or 4 or more units.

In this case the majority of the surgeons, 22 (66,7%) choose to give 2 units of blood and 11 (33,3%) physicians choose 1 unit. No one choose to give 3 or 4 or more units.

In the group of other therapeutics, the majority, 17 (68%) choose to transfuse 2 units of blood, 7 (28%) physicians choose 1 unit, and 1(4%) choose to give 3 units whereas no one chose to give 4 or more units in this scenario.

Figure 8: Units chosen for hypothetical patient in scenario 3

* There was no significant difference between all specialties in choosing units for hypothetical patient in scenario 3. p>0,05 8(30,8%) 18(69,2%) 11(33,3%) 22(66,7%) 7(28%) 17(68%) 1(4%) 0 10 20 30 40 50 60 70 80

1 unit 2 units 3 units

ICU

Surgery

Other therapeutic specialities

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23 Scenario 4- Hemoglobin threshold

- Described a patient after cardiac surgery developing acute myocardial infarction, admitted to the ICU (surgery case).

The majority of the intensive care physicians choose to transfuse at a level of 80 g/L and not to plan a transfusion, out of which 8 (30,8%) choose 80 g/L and 8 (30,8%), choose to not plan a blood transfusion. 7 (26,9%) choose to transfuse at 90 g/L, 2 (7,7%) choose to transfuse at ≥ 100 g/L and 1 (3,8%) choose to transfuse at 70 g/L whereas no one choose to transfuse at 60 g/L.

Among the surgeons the majority of them, 15 (45,5%), choose to not plan a transfusion in this scenario. 8 (24,2%) choose to transfuse at a level of 80 g/L, 5 (15,2%) choose to transfuse at a level of 70 g/L, 4 (12,1%) choose 90 g/L, 1 (3%) choose 60 g/L and whereas no one choose ≥ 100 g/L as a hemoglobin threshold.

In the group of therapeutic physicians the majority, 8 (32%) choose a threshold of 90 g/L, 7 (28%) choose 80 g/L, 6 (24%) of them choose not to plan a transfusion, 4 (16%) choose70 g/L and whereas no one choose a threshold of ≥ 100 g/L.

* There was no significant difference between all specialties in choosing RBC transfusion threshold for scenario 4. p>0,05 1(3,8%) 8(30,8%) 7(26,9%) 2(7,7%) 8(30,8%) 1(3%) 5(15,2%) 8(24,2%) 4(12,1%) 15(45,5%) 4(16%) 7(28%) 8(32%) 6(24%) 0 5 10 15 20 25 30 35 40 45 50 60 g‎/L 70 g‎/L 80 g‎/L 90 g‎/L ≥100 g‎/L I wouldn't plan a transfusion ICU Surgery Other therape utic speciali ties

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24 Scenario 4 – Corresponding units

The majority of the intensivists, 9 (34,6%), choose to transfuse 2 units of blood in this scenario,8 (30,8%) choose 1 unit and 1 (3, 8%) choose to give 4 or more units of blood, whereas no one choose to give 3 units of blood.

The majority of the surgeons, 14 (42,4%), choose to give 2 units of blood, 4 (12,1%) choose to give 1 unit and no one choose to give 3 or 4 or more units.

In the group of other therapeutic physicians the majority, 13 (52%), choose to give 2 units, 6 (24%) choose 1 unit and no one choose to give 3 nor 4 or more units.

Figure 10: Units chosen for hypothetical patient in scenario 4

* There was no significant difference between all specialties in choosing units for hypothetical patient in scenario 4. p>0,05 8(30,8%) 9(34,6%) 1(3,8%) 4(12,1%) 14(42,4%) 6(24%) 13(52%) 0 10 20 30 40 50 60

1 unit 2 units 4 units or more

ICU Surgery

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25 RESULTS OF BLOOD TRANSFUSION TRIGGER IN EACH SCENARIO, COMPARED

BETWEEN ALL SENIOR PHYSICIANS WITH ALL RESIDENT PHYSICIANS Scenario 1

In the group of residents the majority, 30 (51,70%), choose to transfuse at 80 g/L, 23 (39,70%) choose 70g/L, 3 (5,20%) choose 90 g/L, 1 (1,70%) choose 60g/L and also 1 (1,70%) choose to transfuse at ≥100 g/L.

In the group of seniors the majority, 10(38,50%), choose to transfuse at a level of 70 g/L, 8 (30,80%) choose 80g/L, 4 (15,40%) choose 60 g/L and 4 (15,40%) choose 90g/L, whereas no seniors choose the trigger threshold to be at a level of ≥100 g/L.

Figure 11: Hemoglobin threshold for scenario 1, physicians with less years of experience compared with physicians with more years of clinical experience

* There was no significant difference in RBC transfusion threshold between senior physicians compared to resident physicians in scenario 1. p>0,05

1(1,70%) 23(39,70%) 30(51,70%) 3(5,20%) 1(1,70%) 4(15,40%) 10(38,50%) 8(30,80%) 4(15,40%) 0,00% 10,00% 20,00% 30,00% 40,00% 50,00% 60,00% 60 g‎/L 70 g‎/L 80 g‎/L 90 g‎/L ≥100 g‎/L Resident Senior

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26 Scenario 2

In the second scenario, the majority of the residents, 27 (46,60%) choose to transfuse at a level of 80 g/L, 26 (44, 80%) choose 70 g/L, 4 (6,90%) choose 90 g/L, and 1 (1,70%) ≥100 g/L, whereas no resident choose to transfuse at 60 g/L.

The majority of the senior physicians, 17 (65,40%) choose the threshold of 80 g/L, 7 (26,90%) choose 70g/L, 1 (3, 80%) choose 60 g/L, and also 1 (3, 80%) choose 90 g/L whereas no senior physicians choose to transfuse at a level of ≥100 g/L.

26(44,80%) 27(46,60%) 4(6,90%) 1(1,70%) 1(3,80%) 7(26,90%) 17(65,40%) 1(3,80%) 0,00% 10,00% 20,00% 30,00% 40,00% 50,00% 60,00% 70,00% 60 g/L 70 g‎/L 80 g‎/L 90 g/L ≥100 g‎/L Resident Senior

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27 Scenario 3

The majority of the residents, 27 (46,60%), in the third scenario choose to transfuse at the level of 70g/L, 23 (39, 70%) choose 80g/L, 4 (6,90%) choose 60 g/L, 3 (5, 20%) choose 90 g/L, and 1(1,70%) choose to transfuse at the level ≥100 g/L.

In the group of senior physicians the majority, 10 (38,50%), choose to transfuse at a hemoglobin level of 70g/L, 7 (26,90%) choose 80 g/L, 6 (23, 10%) choose 60g/L, 2 (7,70%) choose ≥100 g/L and 1 (3,80%) choose 90 g/L.

4(6,90%) 27(46,60%) 23(39,70%) 3(5,20%) 1(1,70%) 6(23,10%) 10(38,50%) 7(26,90%) 1(3,80%) 2(7,70%) 0,00% 5,00% 10,00% 15,00% 20,00% 25,00% 30,00% 35,00% 40,00% 45,00% 50,00% 60 g/L 70 g‎/L 80 g‎/L 90 g‎/L ≥100 g‎/L Residents Senior

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28 Scenario 4

In the fourth scenario, the majority of the residents which was 22 (37,90%) physicians choose to not plan a transfusion for this scenario, 14(24,10%) choose to transfuse at 80g/L, 12 (20,70%) choose 90 g/L, and 9 (15,50%) choose 70 g/L whereas only 1 (1,70%) choose to transfuse at the level of ≥ 100 g/L.

The majority of the senior physicians, 9 (34,60%), choose to transfuse at the level of 80 g/L, 7 (26,90%) choose to not plan a transfusion and 7 (26, 90%) choose to transfuse at 90 g/L, and 1 (3,80%) choose to transfuse at a level of 60 g/L, 1 (3,80%) choose 70 g/Land 1 (3,80%) choose ≥ 100 g/L.

9(15,50%) 14(24,10%) 12(20,70%) 1(1,70%) 22(37,90%) 1(3,80%) 1(3,80%) 9(34,60%) 7(26,90%) 1(3,80%) 7(26,90%) 0,00% 5,00% 10,00% 15,00% 20,00% 25,00% 30,00% 35,00% 40,00% 60 g‎/L 70 g‎/L 80 g‎/L 90 g‎/L ≥100 g‎/L I wouldn't plan a transfusion Resident Senior

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29 RESULTS OF BLOOD TRANSFUSION TRIGGER IN EACH SCENARIO, COMPARED

BETWEEN SENIOR PHYSICIANS WITH RESIDENT PHYSICIANS IN THE DEPARTMENT OF INTENSIVE CARE

Scenario 1

In the first scenario, the majority of the residents which was 10 (62,50%) of the physicians, choose to transfuse at 80g/L, 5 (31,30%) choose to transfuse at 70g/L, 1 (6,30%) choose 90 g/L, and no one in this group choose to transfuse at 60 g/L or at ≥ 100 g/L.

Among the senior physicians, the majority of them 4(40%), choose to transfuse at 70g/L, 3 (30%) choose 80 g/L, 2 (20%) choose 60 g/L and 1 (10%) choose 90 g/L, whereas no one choose to transfuse at a level of ≥ 100 g/L.

Figure15: Hemoglobin threshold for scenario 1, physicians with less years of clinical experience compared with physicians with more clinical experience in the specialty of intensive care

* There was no significant difference between senior physicians and resident physicians in the department of intensive care for scenario 1. p>0,05

5(31,30%) 10(62,50%) 1(6,30%) 2(20,00%) 4(40,00%) 3(30,00%) 1(10,00%) 0,00% 10,00% 20,00% 30,00% 40,00% 50,00% 60,00% 70,00% 60 g‎/L 70 g‎/L 80 g‎/L 90 g‎/L Residents Seniors

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30 Scenario 2

In the second scenario the majority of the residents choose to transfuse at 70g/L and 80 g/L, out of which 7 (43,80%) choose 70 g/L and 7 (43,80%) choose 80 g/L, 2 (12,50%) choose 90 g/L and no one choose the level of 60 g/L nor to transfuse at a level of ≥ 100 g/L.

In the group of senior physicians, the majority 6 (60%) choose a level of 80 g/L, 3 (30%) choose 70 g/L, 1 (10%) choose 60 g/L, whereas no one choose 90 g/L or ≥ 100 g/L.

Figure 16: Hemoglobin threshold for scenario 2, physicians with less years of experience compared with physicians with more clinical experience in the specialty of intensive care

7(43,80%) 7(43,80%) 2(12,50%) 1(10,00%) 3(30,00%) 6(60,00%) 0,00% 10,00% 20,00% 30,00% 40,00% 50,00% 60,00% 70,00% 60 g/L 70 g‎/L 80 g‎/L 90 g/L Residents Seniors

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31 Scenario 3

In the third scenario the majority of the residents, 8 (50%), choose to transfuse at a level of 70 g/L, 7 (43,80%) choose to transfuse at 80g/L and 1 (6,30%) choose the level of 60 g/L, whereas no one choose to transfuse at the level of 90 g/L or ≥ 100 g/L.

The senior physicians had a majority of 6 (60%) choosing to transfuse at a level of 70g/L, 3(30%) choose 60g/L and 1 (10%) at 80 g/L whereas no one choose a threshold of 90 g/L or ≥ 100 g/L.

Figure 17: Hemoglobin threshold for scenario 3, physicians with less years of experience compared with physicians with more years of clinical experience in the specialty of intensive care

1(6,30%) 8(50,00%) 7(43,80%) 3(30,00%) 6(60,00%) 1(10,00%) 0,00% 10,00% 20,00% 30,00% 40,00% 50,00% 60,00% 70,00% 60 g/L 70 g/L 80 g/L Residents Seniors

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32 Scenario 4

In the fourth scenario the majority of the residents, 7 (43,80%), choose to not plan a transfusion in this case, 6 (37,50%) residents choose to transfuse at 80 g/L, 2 (12,50%) choose to transfuse at 90g/L and 1 (6,30%) choose the level of ≥ 100 g/L, whereas no one choose to transfuse at the level of 60 g/L nor 70 g/L.

The majority of the seniors, 5 (50%), choose to transfuse at a level of 90g/L, 2 (20%) choose 80 g/L, 1 (10%) choose 70g/L, 1 (10%) choose ≥ 100 g/L and 1 (10%) choose to not plan a blood transfusion, and no one choose to transfuse at a Hb level of 60 g/L.

Figure 18: Hemoglobin threshold for scenario 4, physicians with less years of experience compared with physicians with more years of clinical experience in the specialty of intensive care

6(37,50%) 2(12,50%) 1(6,30%) 7(43,80%) 1(10,00%) 2(20,00%) 5(50,00%) 1(10,00%) 1(10,00%) 0,00% 10,00% 20,00% 30,00% 40,00% 50,00% 60,00%

70 g/L 80 g/L 90 g/L ≥100 g/L I wouldn't plan a transfusion

Residents Seniors

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33

DISCUSSION OF THE RESULTS

As earlier discussed the history of blood transfusion threshold has not been clear for many years, the previous “10/30 rule”, stating that the hemoglobin levels should be sustained at a level of 100 g/L or above and a hematocrit above 30% in surgical patients, later on also applied in non-surgical settings such as intensive care units has no clinical evidence leading to its limitation. [4] This rule however, slowly disappeared as blood transfusion showed to have an association of risks for complications such as transfusion related acute lung injury, immunodeficiency, transfusion-associated circulatory overload and other, in turn also increasing the morbidity and mortality of the patients. The rule disappeared some time after that the TRICC choose to evaluate the possible outcome in patients using a lower transfusion trigger (70 g/L) vs. a liber (100 g/L) approach. It was a worry that anemia tolerance would not be sufficient enough especially among critically ill patients. Nonetheless, the results showed to have no difference in morbidity and mortality between the two groups, and also the benefits of transfusion was shown to be at least as effective by using a restrictive approach as using a liberal one. Several published guidelines after this huge clinical trial also recommended a more restrictive approach in various clinical settings. It may be seen as unclear when to transfuse in various clinical settings, strangely even though several studies show that initiating a red blood cell transfusion includes risks and complications, and that it should always be chosen to give blood with a precaution. Evaluating the compensating mechanisms for anemia, i.e. the tolerance for anemia should play a big part in assessing the need for transfusion. Unfortunately there is not much data about clinical practice of RBC transfusion among physicians, and may therefore be discussed very limitedly.

The ruler of this study was an article published about the Canadian physician transfusion practices among critically ill patients, with most of their respondents (57% out of 68,5%), having medical specialties as general internists working for an average of 11.1 (7.1) years in combined medical and surgical intensive care units. Their study used a scenario based survey illustrating different hypothetical scenarios of four different patients with different triggers for a blood transfusion, which was developed after the consultation of experts and an interative process among investigators. However, our study modified the scenarios.

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34 The publication (TRICC) that changed the view of transfusion may have affected the choice of threshold of the participants of this study, but there is no data from previous years showing the threshold in the Kauno Klinikos to compare and assess if there has been any change in practice before and after 1999.

Further on, the first scenario describes a patient, 24-years old (male), admitted to the ICU department after a motor vehicle accident, several fractures and internal lacerations of the spleen and liver was found. Operative interventions such as external fixation and internal fixation were provided for the fractures and laparotomy revealed minor tears of spleen and liver. The Hb concentration of the patient dropped slowly from the normal range over 48 hours, with no evidence of a volume deficit. In our results, the majority (45,2%) of the physicians in the first scenario choose to transfuse at a hemoglobin level of 80 g/L. In a separate point of view between the groups the majority among the intesivists (50%) choose 80 g/L, majority of surgeons (48,5%) choose 70 g/L and the majority among the therapeutic physicians (48%) choose to transfuse at a level of 80 g/L. There was no significant difference between these different specialties (p>0, 05). And the majorities in all specialties choose to transfuse with 2 units of blood for the first scenario. In comparison to the results concluded in the Canadian study, their results showed that 63% of their respondents choose a hemoglobin threshold of 70 g/L [23] for the first scenario. According to practice guidelines and recommendation a restrictive approach should be used in critically ill trauma patients (when Hb falls below a concentration of 70 g/L) and [26] in addition to this, studies have shown that a restrictive approach in trauma patient is safe to use. [32] Regarding units for blood transfusion in trauma critically ill patients, there is not much data about this, our understanding is that it will always be individual to the case and also to keep a low number of unit(s) in turn deceases the amount of blood transfused thus decrease risk for complications. However, to maintain the Hb at least over 70 g/l could be used as a guide to choose units of RBC. With that said the majority in Kauno Klinikos did not choose the exact level of Hb as according guideline recommendations but was yet close to the restrictive approach (70 g/L) rather than the liberal approach (100 g/L). Also 2 units seemed to be appropriate in this case according to the majority of the physicians.

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35 In the second scenario, 70 years old patient (female) with gastrointestinal hemorrhage was admitted to the ICU after vomiting of approximately 1 L of blood, additionally having signs of hematochezia and melena. Even though crystalloids was provided for the patient and she was hemodynamically stable at the moment and no signs of volume deficit was found, she was still having an evidence of blood loss in a rate of 2 units every 12 hours. Due to the clinical trials that has been performed to assess the Hb threshold among critically ill patients (which are still today evaluated and studied), it could be concluded that the strategy of transfusion in critically ill patients is recommended to be restrictive, and a liberal approach include higher risks for complications, also a increased morbidity and mortality. [23, 33] However, the requirements for patients with acute hemorrhage is thought to differ from the other recommendations, due to the fact that acute hemorrhage may contribute to a fast hemodynamic instability, and also a fast decrease in Hb concentration (which is thought to be due to the fact that hemoglobin values may underestimate the blood loss). [33] Guidelines for blood transfusion are mainly based on clinical trials excluding the patients with acute bleeding. [21] The British Society of Gastroenterology from 2002 recommends a hemoglobin concentration of ≤ 100 g/L as a threshold for hemorrhage transfusion. [34] Other guideline recommendations from 2010, which based the conclusion on systematic reviews and clinical trials, stated that a blood transfusion should not be initiated (in a patient with non-variceal bleeding) until hemoglobin level falls below 70 g/L or less. [38] In addition to this, in a randomized clinical trial, the restrictive vs the liberal approach of blood transfusion were assessed in patients with acute gastrointestinal bleeding. The conclusion of the study was that a restrictive approach (70 g/L) was safe and improved the clinical outcomes in comparison with the ones receiving a liberal (100 g/L) approach, as it was reported that risk of rebleeding risks was decreased, survival rate were increased and the need for rescue therapy and other complication was markedly decreased. Although this study had good results, it also had some limitations and the results cannot be generalized to all patients with acute gastrointestinal bleeding. [35] In another single-center, randomized controlled trial study, to further more show the possible or appropriate threshold for hemorrhagic patients, it was stated that the outcomes in patients receiving a restrictive approach significantly improved. [33]

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36 Our results showed that the majority of the physicians (52, 4%) choose a hemoglobin threshold of 80 g/L. In a detailed view, the majorities (50%), in the group of intensivists choose 80 g/L, the majorities (54, 5%) of the surgeons choose 70g /L, and the majorities (68%) of the other therapeutic physicians choose an Hb level of 80 g/L. There was no significant difference between these different specialties (p>0, 05). The majority of the physicians choose 2 units for this scenario. The same results were seen in among the Canadian physicians, which also choose to transfuse at a level of 80 g/L. However, there is not enough data found for the most suitable threshold, but the ones that do show results of patients with gastrointestinal bleeding show clearly that a restrictive threshold for blood transfusion could be appropriate to use in that group of patients. Again every transfusion includes risks and complication so no matter what threshold it should always be given with caution.

In the third scenario, a 45- year old patient (male) is presented to the ICU after 3 days of productive cough, fever and chills. There was a suspicion of sepsis, and the patient had pneumonia seen on X-ray. The patient was intubated and mechanically ventilated and his arterial saturations are determined to be 94 % on 50 % oxygen. After aggressive volume resuscitation, his hemoglobin level dropped with no evidence of ongoing blood loss. In this scenario the majority (44%) of the physicians choose to transfuse the patient with severe sepsis at a level of 70 g/L. In a more specific view among the different specialties, the majority of the intensivists (53,8%) choose a Hb concentration of 70 g/L the majority (36,4%) of the surgeons choose 70 g/L, and the majority of other therapeutic specialties was divided, (44%) choosing a level of 70 g/L and (44%) 80 g/L. There was no significant difference between these different specialties (p>0, 05). And the majority of the physicians chose 2 units for this scenario. The same results were found in the Canadian article with the majority of their physicians choosing 70 g/L as a threshold for the septic patient. In an updated systematic review from 2016, it was concluded that a more restrictive approach was safe to use. In addition to this, guidelines state that the Hb target is similar for patients with sepsis as the critically ill patients. [11] The threshold chosen is what we believe would be the most appropriate Hb trigger concentration based on current guidelines, also liberal strategies have yet no been proven to have a more beneficial outcome compared to a restrictive one, except in patients who has acute MI.

The fourth and last scenario, presents a case about a 55 years old patient (male) that after four days of cardiac surgery (uncomplicated abdominal aortic aneurysm repair), developed an anterior wall myocardial infarction. He was admitted to the ICU with no other complications and there is no evidence of volume deficit, also the patient is currently pain free. To discuss the possible threshold of

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37 blood transfusion in myocardial infarction (MI) it may be necessary to remind us of the effects anemia has in a patient with acute coronary syndrome. The answer is that anemia is not thought to be well tolerated in patients with coronary diseases as in other clinical conditions. [21] In addition to this, patients with coronary diseases often receive treatment in combination between anticoagulants and invasive events, which in turn increases the chances of having an episode of bleeding. Subsequently the bleeding leads to anemia, which in case of acute coronary syndrome worsens the ischemia of the heart. [36] Recommendations from the American Associations of Blood Banks states that a threshold of 80 g/L should be used in patients with cardiovascular diseases [7] and studies have concluded that a restrictive transfusion strategy may be more suitable for critically ill patients who are not suffering from a cardiovascular disease, but should be used with caution in those who do. In a systematic review from 2016, the threshold was concluded to be 80 g/L in patients with an ongoing acute coronary syndrome or chronic cardiovascular disease. [37] The results of our physicians show us that the majority, 29 (34,5%) choose to not plan a transfusion. The majority of the intensive care physicians choose to transfuse at a level of 80 g/L and not to plan a transfusion, out of which 8 (30,8%) choose 80 g/L and 8 (30,8%), choose to not plan a blood transfusion. Among the surgeons the majority of them, 15 (45,5%), choose to not plan a transfusion and in the group of therapeutics the majority choose 8 (32%) choose a threshold of 90 g/L. This was an additional and modified option added to this survey, which was thought to be chosen due to the lack of knowledge about blood transfusion in patients suffering from acute coronary syndrome. We believe that this option is not the most suitable choice since anemia may limit the oxygen delivery to the heart in patients with existing coronary lesions. However, due to the fact that the patient was hemodynamically stable and there were no data about the Hb concentration in this scenario, the choice to not planning a transfusion is understandable.

Another part of this study was to evaluate if there is any difference in when to initiate a RBC transfusion between physicians with more years of clinical experience compared with the ones who are younger and therefore have less years of experience. The results show us that there is no significant difference among the total younger physicians included compared to the total older physicians in this study. This tells us that among the physicians in Kauno Klinikos, they are well educated regarding blood transfusion and most of the results show that they follow the guidelines with a more restrictive approach in most of the hypothetical cases distributed in this study.

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38 In addition, this particular study was done in the intensive care unit and was therefore also more detailed on the physicians working as intensive care physicians and was therefore specifically divided into younger and older ones only in this group and the results showed to have no significant difference (p>0,05) when choosing a hemoglobin threshold for each scenario provided in this study.

To summarize the discussion it can be said that the physicians of the Kauno Klinikos do have a restrictive approach in terms of blood transfusion, although the knowledge concerning a patient with acute myocardial infarction does not seem to be clear. It is important to keep in mind that whatever situation, the transfusion threshold, when chosen should be at a level where maximum benefit and minimal harm can be given to the patient.

CONCLUSION

1. The physicians at Kauno Klinikos hospital showed to have an overall great knowledge in most of the clinical settings provided in this scenario based survey regarding hemoglobin threshold and when to initiate a blood transfusion.

2. There is no difference on blood transfusion threshold between younger and older physicians working in intensive care unit.

3. Participated physicians showed to have a more restrictive approach and a practice according recommended guidelines.

4. The years of experience do not seem to determine if experience has any influence when it comes to blood transfusion.

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39

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001991/

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626470/#b67-blt-11-193

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781778/

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Guidelines From the AABB. JAMA [Internet]. 2016 [cited 22 November 2016];316(19):2025. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27732721

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9. Napolitano L, Kurek S, Luchette F, Corwin H, Barie P, Tisherman S et al. Clinical practice guideline: Red blood cell transfusion in adult trauma and critical care*. Critical Care Medicine [Internet]. 2009 [cited 23 November 2016];37(12):3124-3157. Available from:

https://www.ncbi.nlm.nih.gov/pubmed/19773646

10. Hamm C, Bassand J, Agewall S, Bax J, Boersma E, Bueno H et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal [Internet]. 2011 [cited 23 November 2016];32(23):2999-3054. Available from: https://www.ncbi.nlm.nih.gov/pubmed?term=21873419

Blood transfusion practice among medical physicians working at Kauno Klinikos Hospital