Appendix 1 |
|Appendix D:||Practice Guidelines for Blood Component Therapy|
Adverse Effects of Diminished Oxygen-carrying Capacity
Diminished oxygenation due to inadequate oxygen-carrying capacity can have serious clinical implications, primarily because of ischemic effects on the myocardium and brain. Oxygen delivery (DO2) is defined as the product of cardiac output (Qt) and arterial oxygen content (CaO2 ). The latter is a function of hemoglobin saturation (SaO2 ), hemoglobin concentration (Hb), and the amount of oxygen physically dissolved in arterial blood:
DO2 = (CaO2)(Qt),
CaO2 = (SaO2/100)(1.39.Hb) + (0.003.PaO2).
Although an increase in cardiac output is the primary compensation for reduced oxygen-carrying capacity, changes in the microcirculation can affect oxygen transport at the tissue level. For example, during periods of blood loss, the autonomic nervous system can restrict blood flow and oxygen delivery to skin, muscle, and the abdominal viscera to preserve oxygen delivery to the central nervous system and heart.
The effects of anemia must be separated from those of hypovolemia, although both can interfere with oxygen transport. The clinical manifestations of hypovolemia are well known, and a classification based on blood loss has been established by the American College of Surgeons. 51 A loss of up to 15% of total blood volume (class I hemorrhage) usually has little hemodynamic effect other than vasoconstriction and mild tachycardia. A loss of 15-30% of blood volume (class II hemorrhage) produces tachycardia and decreased pulse pressure; unanesthetized patients may also exhibit anxiety or restlessness. A loss of 3040% (class III hemorrhage) produces increasing signs of hypovolemia, including marked tachycardia, tachypnea, and systolic hypotension; unanesthetized patients demonstrate altered mental status. Experience has shown that, in young healthy patients, losses of up to 3040% of blood volume usually can be treated adequately with crystalloid therapy. Loss of more than 40% of total blood volume (class IV hemorrhage) is life-threatening and accompanied by marked tachycardia and hypotension, very narrow pulse pressure, and low urine output; mental status is markedly depressed.
The lower limit of human tolerance to acute normovolemic anemia has not been established. It is believed that oxygen delivery is adequate in most individuals at hemoglobin concentrations as low as 7 g/dL. 4 In healthy, normovolemic individuals, tissue oxygenation is maintained and anemia tolerated at hematocrit values as low as 1825%. 52, 53 The heart does not begin producing lactic acid until a hematocrit of 15-20% is reached. 54, 55 Myocardial lactate flux does not appear to be affected at hemoglobin concentrations as low as 6 g/dL. 56 Heart failure usually does not occur until the hematocrit reaches 10%. 57, 58
Chronic anemia is better tolerated than acute anemia. Oxygen delivery is facilitated through increases in 2,3-diphosphoglycerate levels in RBCs. In patients with chronic anemia, cardiac output usually does not change until the hemoglobin concentration falls below 7 g/dL. Significant symptoms are unusual unless the RBC mass is decreased by approximately 50%. 58 Chronic anemia has special implications for pregnant women. Obstetric patients usually tolerate chronic anemia without significant adverse maternal or fetal effects. A review of 17 studies of obstetric patients revealed no effect of hemoglobin concentration on the incidence of stillbirth or intrauterine growth retardation, 59 whereas another found increased complications of pregnancy associated with both low (<10.4 g/dL) and high (>13.2 g/dL) hemoglobin concentrations. 60 Studies of acute isovolemic anemia in animals suggest that fetal oxygen extraction is maintained until the maternal hematocrit is reduced by more than 50%. 61 In a study of pregnant sheep with chronic anemia (hematocrit less than 14% for 6 days), decreased oxygen delivery to the placenta did not reduce fetal oxygen consumption. 62
In acute anemia, reductions in arterial oxygen content usually are well tolerated because of compensatory increases in cardiac output. This compensatory mechanism may be affected by several factors, however, such as left ventricular, dysfunction and vasoactive pharmacologic agents ( e.g., &bgr; adrenergic or calcium channel blockade), necessitating a higher hemoglobin concentration for adequate oxygen delivery. Human tolerance of acute anemia is further affected by certain pharmacologic agents, such as anesthetics, hypnotics, and neuromuscular blocking drugs, and by intraoperative conditions ( e.g., hypothermia). Anesthetics have important cardiovascular and endocrine actions that influence oxygen transport and consumption and the physiologic response to acute anemia. Most anesthetics cause myocardial depression and decrease arterial blood pressure, cardiac output, stroke volume, peripheral vascular resistance, total-body oxygen consumption, and cerebral and myocardial oxygen demands. 63 The magnitude of these effects varies among anesthetics and as a function of anesthetic depth. In addition, anesthetics differ in their effects on hepatic blood flow, and thus they may differ in how they influence the development of systemic lactic acidosis and base-deficit in patients with anemia or impaired oxygen transport.
The physiologic limit of oxygen transport is not known in either awake humans or those under general anesthesia. Case reports suggest that humans may tolerate lower hemoglobin concentration and oxygen transport during anesthesia than when awake. 64 This may be due to an anesthetic-and neuromuscular block-ade-induced reduction of oxygen consumption. However, there are no controlled prospective studies addressing this important issue. The impact of regional anesthesia on oxygen transport is also unclear.
These physiologic principles have been reinforced by clinical studies demonstrating inconsistent associations between anemia and adverse perioperative or peripartum outcomes. Case series reports of Jehovah's Witnesses indicate that some patients tolerate very low hemoglobin concentrations (less than 68 g/dL) in the perioperative period without an increase in mortality. 65, 66, 67 A review of 16 series published between 1983 and 1990, involving 1,404 operations on Jehovah's Witnesses, found that lack of blood was implicated as the primary cause of death in only 8 (0.6%) patients and as a contributor to death in an additional 12 (0.9%) patients. 68 Another review of 61 reports of 4,722 Jehovah's Witnesses identified 23 deaths due to anemia, all but 2 of which occurred at hemoglobin concentrations less than 5 g/dL. 64 A stastistical analysis of one series of Jehovah's Witnesses found that hemoglobin alone was not a statistically significant predictor of outcome unless it was less than 3 g/dL. 69 Both hemoglobin and intraoperative blood loss must be taken into consideration. 65 This body of literature represents self-selected reports, however, in which clinicians are more likely to report survivors than nonsurvivors. The information provided in most reports is insufficient to allow for independent conclusions regarding the degree to which profound anemia contributed to morbidity or mortality.
Decisions regarding perioperative transfusion are often difficult, necessitating clinical judgment. There is little scientific support for relying on a specific hemoglobin or hematocrit value as a transfusion trigger, such as the outdated 10/30 rule that transfusion is necessary in patients with a hemoglobin concentration less than 10 g/dL or an hematocrit less than 30%. 70 Estimates of blood volume are also unreliable, because of inaccuracies of intraoperative blood loss measurement, intercompartmental fluid shifts during surgery, and the dilutional effects of crystalloid therapy. Although often useful, intraoperative hemoglobin determinations can be misleading. Alterations of intravascular volume due to the concomitant administration of colloids and crystalloids can produce artificially lowered or elevated hemoglobin concentrations.
Intraoperative estimates of blood volume are indirect, being inferred from pressure measurements obtained at various locations (arterial, central venous, or pulmonary capillary wedge pressures). Whole-body oxygen consumption, oxygen extraction ratio, and oxygen delivery have been used to estimate the need for RBC transfusion. 71, 72, 73 These measurements require invasive monitoring ( e.g., arterial, pulmonary artery), have not been independently verified, and are global (not organ-specific) measures of oxygen utilization. In the clinical setting, it is not possible to directly measure the adequacy of oxygen transport to specific organs or to regions within these organs.
The perioperative decision-making process regarding transfusion is complicated by knowledge that myocardial ischemia is often silent and most frequent in the postoperative period, when monitoring is less intense. 74, 75 A patient's oxygen transport needs can increase at any time during the postoperative period because of pain, fever, shivering, or physical activity.
Aside from the more obvious potential benefits of RBC transfusion in improving oxygen-carrying capacity, other unsubstantiated claims of benefit have been made, including effects on wound-healing. However, in healing tissue, collagen deposition is dependent on oxygen tension and perfusion and not on blood hemoglobin concentration. 76
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