Transfusion therapy

1

What is the overarching indication for blood transfusion?

The overarching indication for transfusing packed red blood cells (RBCs) is to improve oxygen delivery ( $\dot{D}{O}_2$ ). One of the primary roles of RBCs is to transport oxygen from the lung to tissue to allow aerobic metabolism. $\dot{D}{O}_2$ is dependent upon the cardiac output (CO) and the arterial oxygen content (CaO ₂ ) by the following equation:

Where arterial oxygen content equals the following:

Hg, hemoglobin; S _a O ₂ , arterial oxygen saturation; P _a O ₂ , arterial oxygen partial pressure

In other words, oxygen delivery to tissue, $\dot{D}{O}_2$ , is dependent upon the amount of oxygen in the blood, CaO ₂ , and the rate, CO, that blood is delivered. There are circumstances (e.g., hemorrhage) in which the $\dot{D}{O}_2$ is inadequate to meet the body’s metabolic oxygen demands ( $\dot{V}{O}_2$ ). Transfusing RBCs will increase the Hg level, thereby, increasing CaO ₂ , which increases $\dot{D}{O}_2$ . Also, transfusing RBCs (and other blood products) will increase the heart’s preload and subsequent stroke volume (recall Frank-Starling law), leading to an increase in CO which also increases $\dot{D}{O}_2$ . Recall, CO = stroke volume × heart rate. Therefore transfusing RBCs will increase $\dot{D}{O}_2$ by increasing both oxygen content and CO.

2

What happens when there is a mismatch between oxygen delivery and consumption (aka supply-demand mismatch)?

$\dot{D}{O}_2$ , usually exceeds oxygen consumption, $\dot{V}{O}_2$ , by a factor of 4 (1000 mL/min vs. 250 mL/min). In other words, oxygen supply to tissue greatly exceeds tissue oxygen demands at rest. However, when $\dot{D}{O}_2$ is inadequate to meet $\dot{V}{O}_2$ demands, a compensatory increase in “oxygen extraction” occurs to maintain $\dot{V}{O}_2$ . Normally, the oxygen extraction ratio (O ₂ ER) is 20% to 30% where O ₂ ER = $\dot{V}{O}_2$ / $\dot{D}{O}_2$ . For example, if $\dot{V}{O}_2$ , is normally 250 mL/min and $\dot{D}{O}_2$ , is 1000 mL/min, then the O ₂ ER = 25%. This corresponds to a mixed venous saturation (S _mv O ₂ ) equal to 70% to 80%. Note, that a S _mv O ₂ requires right heart catheterization with a pulmonary artery catheter to sample blood from the pulmonary artery. Normally, a compensatory increase in CO will occur to maintain adequate $\dot{D}{O}_2$ in the setting of increased $\dot{V}{O}_2$ (e.g., exercise). If the increase in CO fails to maintain adequate $\dot{D}{O}_2$ , then the oxygen extraction ratio will increase causing the S _mv O ₂ less than 70%. Once these compensatory mechanisms are exhausted, cells switch to anaerobic metabolism (i.e., lactic acidosis). For example, a clinical correlate associated with inadequate $\dot{D}{O}_2$ is cardiogenic shock caused by inadequate CO or hemorrhagic shock caused by inadequate oxygen content from acute blood loss anemia and inadequate CO from hypovolemia.

3

What is $\dot{D}{O}_{\mathrm{2crit}}$ ?

$\dot{D}{O}_{2\text{crit}}$ is defined as the critical oxygen delivery needed to satisfy the metabolic demands for oxygen consumption. In a euvolemic patient with normal cardiac function, the $\dot{D}{O}_{2\text{crit}}$ is normally not reached until the Hg concentration decreases to 3.5 g/dL. However, the specific Hg level depends upon the patient’s oxygen requirement. For example, in high metabolic states (e.g., sepsis, burns, trauma) there is an increase in $\dot{V}{O}_2$ ; therefore $\dot{D}{O}_{2\text{crit}}$ is reached at a higher concentration of Hg. Comorbidities, such as coronary artery disease also affects the Hg concentration at which $\dot{D}{O}_{2\text{crit}}$ is reached.

4

What are some of the surrogate measures for $\dot{D}{O}_{\mathrm{2crit}}$ ?

$\dot{D}{O}_{2\text{crit}}$ cannot be directly measured in the typical clinical setting. Surrogate variables include:

• Vital signs: hypotension, tachycardia, urine output

• Labs: lactic acid, base deficit

• Signs of myocardial ischemia: new ST-segment depression greater than 0.1 mV, new ST-segment elevation greater than 0.2 mV, regional wall motion abnormalities by echocardiography

• Decreased mixed venous O ₂ saturation (< 50%)

5

What are the physiological adaptations to acute normovolemic anemia?

Acute normovolemic anemia occurs secondary to the replacement of intraoperative blood loss with crystalloid solution. The compensatory physiological changes include sympathetic stimulation (tachycardia, increased CO), decreased blood viscosity (decreases afterload, increases preload, improves capillary flow), and redistribution of blood flow to tissues that are more oxygen dependent (i.e., heart and brain). Notably, the heart and brain have the highest O ₂ ER at baseline and cannot tolerate a decrease in $\dot{D}{O}_2$ by increasing oxygen extraction compared with other tissues.

6

What does a low mixed venous saturation suggest in terms of oxygen delivery?

A low mixed venous saturation (S _mv O ₂ < 60%) implies that the body is increasing its O ₂ ER because of decreased $\dot{D}{O}_2$ . This implies that either the CO and/or oxygen content is insufficient to meet the metabolic demands of the body. This is commonly seen in the setting of cardiogenic and hemorrhagic shock.

7

Can a patient develop lactic acidosis despite a normal mixed venous saturation?

Some patients may present with shock physiology (anaerobic metabolism as indicated by lactic acidosis) not because of inadequate $\dot{D}{O}_2$ but rather because of inability to use oxygen because of impairment of oxidative phosphorylation. This can be seen in septic shock (endotoxin-mediated inhibition of pyruvate dehydrogenase), cyanide toxicity (inhibits electron transport chain), propofol infusion syndrome (inhibits electron transport chain).

8

Which organ has the highest oxygen extraction ratio?

The heart has the highest O ₂ ER and consumes more oxygen by mass compare to any other organ. This is evident by the fact that the coronary sinus has the lowest oxygen saturation in the entire body (SvO ₂ ≈ 40%), which also explains why the mixed venous saturation from the pulmonary artery (SmvO ₂ ≈ 70%) is lower than the central venous saturation from the superior and inferior vena cava (ScvO ₂ ≈ 75%). It also explains the rationale in maintaining a higher Hg in patients with coronary artery disease as the heart’s oxygen demands can increase up to a factor of five when stressed (e.g., tachycardia caused by shock physiology), but has limited ability to compensate for anemia by increasing its O ₂ ER.

9

What Hg concentration should trigger a blood transfusion?

The Transfusion Requirements in Critical Care Trial attempted to answer this question. Within the trial, groups were divided into a restrictive trigger of 7 g/dL (to target a Hg between 7 and 9 g/dL) and a liberal trigger of 10 g/dL (to target a Hg between 10 and 12 g/dL). The 30-day mortality was found to be lower in the restrictive group, with organ dysfunction being comparable between the two groups. Further, the restrictive group received less blood transfusions during the intensive care unit (ICU) stay. It was determined from this trial that the transfusion trigger for most patients in the ICU should be a Hg less than 7 g/dL. However, patients with hemodynamic instability or evidence of cardiac ischemia may need a higher Hg threshold.

Current American Society of Anesthesiology (2015) guidelines recommend to strongly consider transfusion of RBC when the Hg is less than 6 g/dL, that transfusion is rarely needed when the Hg is greater than 10 g/dL, and that clinical indications (e.g., ongoing blood loss) should guide transfusion triggers when the Hg is between 6 and 10 g/dL.

10

What is leukoreduction? What are its benefits?

Leukoreduction is the process by which white blood cells are removed from donor blood through the use of a filter. It is reported to have the following benefits: (1) reduces the risk of febrile, nonhemolytic transfusion reactions, and (2) reduces the transmission of infectious agents, such as Epstein-Barr virus, cytomegalovirus, human T-cell lymphocytic virus, prion disease (Creutzfeldt-Jakob disease), malaria, leishmaniasis, human granulocytic anaplasmosis, and yersinia enterocolitis. Universal leukoreduction is currently practiced in mostly all developed countries, aside from the United States, where its adherence is not mandated (because of costs/benefit concerns). However, in practice the vast majority (> 80%–90%) of hospitals in the United States adhere to universal leukoreduction of all blood products.

11

What are the risks of blood transfusion?

• Infectious transmission

• Transfusion reactions (see Table 11.1 )

  Table 11.1

  Major Transfusion Reactions

  Modified from Boshkov LK. Transfusion-related acute lung injury and the ICU. Crit Care Clin. 2005;21:479-495.

  Diagnostic Entity	Onset	Major Signs and Symptoms	Differentiating Features
  Transfusion-related acute lung injury (TRALI)	Minutes to hours	Dyspnea, respiratory distress, hypoxemia, cyanosis, pulmonary edema, fever, tachycardia	Nonhydrostatic pulmonary edema, frequent fever, transient leukopenia
  Transfusion-associated circulatory overload (TACO)	Minutes to hours	Dyspnea, respiratory distress, hypoxemia, cyanosis, pulmonary edema, evidence of hypervolemia (jugular venous distention, peripheral edema, elevated BNP), hypertension	Hydrostatic pulmonary edema, absent fever, hypertension, evidence of hypervolemia, evidence of increased left atrial pressure, elevated BNP, responds to diuretics
  Anaphylactic reactions	Minutes to hours	Bronchospasm, respiratory distress, hypotension, cyanosis, generalized erythema and urticaria, mucous membrane edema	Rash, urticaria, and edema present; hypotension and bronchospasm prominent
  Bacterial contamination of blood products	Minutes	Fever, rigors, hypotension, and vascular collapse	Fever, rigors, and vascular collapse predominant; most common with platelets
  Hemolytic transfusion reaction	Minutes	Fever, rigors, hypotension, hemoglobinuria, disseminated intravascular coagulation	Usually with red blood cell transfusion, hemolysis

  Symptoms may be missed while under general anesthesia, and differential diagnosis should be expanded to include common intraoperative problems.

  BNP , Brain natriuretic peptide.

• Immunomodulatory effects

12

Describe the risk of infection that can occur with blood transfusion

Blood transfusion is extremely safe in this day and age. The risk of transmission of hepatitis C or human immunodeficiency virus (HIV) from a unit of blood is rare in developed nations (one in few million on average) and is highly dependent upon the population. For example, in Canada the risk of hepatitis C and HIV with blood transfusion is reported to be 1 in 13 and 21 million, respectively. However, there will always remain some risk, albeit rare, of infection with blood transfusion. These include pathogens that are routinely tested, including those without a screening test. The pathogens routinely tested include the following: hepatitis, HIV, syphilis, human T-cell lymphotropic virus, West Nile virus, and cytomegalovirus. Other pathogens that may be transmitted include prion-mediated disease (Creutzfeldt-Jakob disease) in the United Kingdom, parasitic diseases, such as Chagas disease, and malaria in underdeveloped regions of the world.