The universal goal of resuscitation is to maintain oxygen uptake (VO2) into the vital organs and thereby sustain aerobic metabolism. The determinants of oxygen uptake are identified in the equation shown below.
VO2 = Q x Hb x 13 x (SaO2 – SvO2)
The factors that pose a risk to the VO2 in acute blood loss are the cardiac output (Q) and the hemoglobin concentration (Hb). The consequences of a low cardiac output are far more threatening than the consequences of anemia. Therefore, the first priority in acute blood loss is to preserve blood flow (cardiac output), while correcting erythrocyte deficits is a secondary goal.
FLOW-DIRECTED RESUSCITATION
Each of the fluids was infused in the volume indicated over 60 minutes, and the height of the columns indicates the change in cardiac index recorded at the end of the infusion period. The volumes of whole blood, packed cells, and dextran-40 are equivalent (500 mL), whereas the infusion volume of lactated Ringer’s (1 L) is double that of the other fluids. The most potent fluid for promoting the cardiac output is the dextran-40, and the least potent resuscitation fluid is the erythrocyte concentrate (packed RBCs).
Blood Products
If promoting cardiac output is the first priority in the management of acute hemorrhage, then blood is not the ideal resuscitation fluid for acute blood loss because blood products do not promote blood flow as well as some acellular fluids. The density of erythrocytes impedes the ability of blood products to promote blood flow (a viscosity effect). In fact, the administration of erythrocyte concentrates (packed cells) can reduce blood flow and aggravate tissue oxygen deficits.
Asanguinous Fluids
The dextran-40 represents one type of fluid, which is characterized by the presence of large molecular weight substances that do not pass easily from one fluid compartment to another. These large molecules with limited mobility prevent the egress of water, and this maintains the volume of the fluid compartment. Fluids of this type that restrict water movement are called colloids (from the Greek word for glue). The other type of fluid is the lactated Ringer’s solution, which is an electrolyte solution devoid of large molecules that impede water movement. Fluids of this type that allow water to move freely from one fluid compartment to another are called crystalloids.
This difference cannot be explained by viscosity, because both types of fluids are acellular and have negligible viscosities. The difference is due to the differences in volume distribution. Crystalloid fluids are primarily sodium chloride solutions, and because sodium is distributed evenly in the extracellular fluid, crystalloid fluids will also distribute evenly in the extracellular fluid. Because plasma represents only 20% of the extracellular fluid, only 20% of an aliquot of crystalloid fluid will remain in the vascular space, while the remaining 80% will add to the interstitial space. On the other hand, colloid fluids, because of their limited mobility, are more prone to remain in the vascular space. In the case of dextran-40, between 75 and 80% of the infused volume will remain in the plasma. Therefore, the enhanced effect of colloids on the cardiac output is due to the greater tendency of colloid fluids to increase the plasma volume. The increase in plasma volume augments cardiac output not only by increasing ventricular preload (volume effect) but also by decreasing ventricular afterload (dilutional effect on blood viscosity).
The following statements summarize some salient features of resuscitation fluids.
1. Colloid fluids are superior to blood products and crystalloid fluids for promoting blood flow (cardiac output).
2. Erythrocyte concentrates (packed cells) do not increase (and can decrease) blood flow, and thus they should never be used for volume resuscitation.
3. Crystalloid fluids primarily fill the interstitial space.
4. To have equivalent effects on cardiac output, the volume of crystalloid fluid infused must be at least three times greater than the volume of colloid infusion.
Despite the superior performance of colloid fluids, crystalloid fluids are more popular for volume resuscitation. This preference is partly due to the lower cost of crystalloid fluids, and partly due to habit. Chapter 15 expands further on the various likes and dislikes of colloid and crystalloid fluids.
Fluid Administration
The standard approach to volume resuscitation in hypovolemic shock is to rapidly administer 2 L of crystalloid fluid as a bolus, or infuse crystalloid at a rate of 6 mL/min/kg (31a). If a favorable response is seen, then crystalloid fluids are continued using the endpoints discussed below. If there is not a favorable response, then colloid fluids and blood products are added to the regimen. The rate of infusion is dictated by the clinical condition of the patient and will vary widely. Infusion rates as high as 2.5 mL/second can be delivered through introducer catheters. A rough estimate of the resuscitation volume can be derived as follows.
1. Remember to use lean body weight and to adjust for obesity and advanced age.
2. Clinical manifestations may not be prominent in mild volume loss, but aggressive volume infusion is not indicated in that setting. Once blood pressure drops in the supine position, there is at least a 30% decrease in blood volume.
3. Calculate the volume deficit by multiplying the estimated normal blood volume and the percent loss. This is a quantitative estimate of the volume needs in each patient.
4. Determine the resuscitation volume of specific fluids using the rules listed below.
a. Blood replacement is usually not necessary for Class I and Class II hemorrhage.
b. Although colloid fluids can differ in their ability to remain in the vascular compartment, a general rule of thumb is to assume that no less than 50% and no more than 75% of infused colloid will remain in the vascular space. This translates to a replacement volume for colloid fluids that is 1.5 to 2 times the volume deficit.
c. The resuscitation volume for crystalloid fluids is 4 times the volume deficit, or 3 times the resuscitation volume for colloids.
ENDPOINTS
The following are common endpoints of volume resuscitation:
1. CVP = 15 mm Hg (32)
2. Wedge pressure = 10 to 12 mmHg (33)
3. Cardiac index > 3 L/min/m2
4. Oxygen uptake (VO2) > 100 mL/min/m2
5. Blood lactate < 4 mmol/L
6. Base deficit -3 to +3 mmol/L
These endpoints represent normal hemodynamic parameters for adults.
Base Deficit
The base deficit (millimoles of base needed to correct the pH of 1 L of whole blood to 7.40) has been shown to correlate with volume deficits and with mortality in trauma victims. As a result, this parameter has been recommended as a valuable guide to volume therapy. The base deficit is routinely calculated by many automated blood gas analyzers, and the calculated base deficit is included in many blood gas reports. The normal range for the base deficit is 3 mmol/L on either side of zero. Elevations in base deficit can be classified as mild (2 to 5 mmol/L), moderate (6 to 14 mmol/L), or severe (> 15 mmol/L).
The base deficit that remains elevated during volume infusion is an indication of ongoing tissue ischemia. This measurement is probably a poor man’s lactate determination, and it shows promise as a readily available and easy-to-use index of ischemic acid production in tissues.
ERYTHROCYTE RESUSCITATION
In the second stage of management, attention is directed to deficits in oxygen carrying capacity. The current practice of transfusing red blood cells based on hemoglobin determinations has absolutely no scientific basis. A serum hemoglobin concentration provides no information about tissue oxygenation, nor is it synonymous with oxygen carrying capacity. To illustrate the latter point, when dehydration increases the serum hemoglobin concentration, does it also increase the oxygen carrying capacity of blood?
The move away from hemoglobin and hematocrit is apparent in the Clinical Guideline on Elective Red Cell Transfusions published by the American College of Physicians. The guideline states that for asymptomatic patients with anemia, “In the absence of patient risks (e.g., active coronary disease), transfusion is not indicated, independent of hemoglobin level”(italics mine).
Oxygen Transport Variables
A more rational approach to red cell transfusions is to employ the oxygen transport variables and the blood lactate level to assess tissue oxygenation. The following conditions would be indications for transfusion in normovolemic anemia:
1. Oxygen uptake (VO2) below the normal range (indicating an oxygen debt)
2. Blood lactate greater than 4 mmol/L (regardless of the VO2)
3. Oxygen extraction ratio (O2ER) greater than 0.5
The VO2 can also be used to evaluate the response to transfusion therapy. An increase in VO2 after transfusion of one unit of blood or packed cells indicates a beneficial response. Transfusion of single units of blood can then be continued until the VO2 is no longer augmented.
OTHER CONCERNS
RESUSCITATION-INDUCED HEMORRHAGE
Although the prevailing opinion favors aggressive volume resuscitation for hemorrhage, evidence from both animal studies and clinical trials indicates that volume resuscitation to normotension can actually promote continued blood loss. This is an important observation for two reasons. First, it indicates that the blood pressure is not an appropriate endpoint for the resuscitation of hypovolemic shock (not, at least, until holes in blood vessels are sealed). Second, and more important, it implies that therapy aimed at achieving normal clinical parameters (which is the general approach in modern medicine) is not appropriate when the human body is subjected to abnormal conditions. Normal clinical parameters are a desirable goal only when abnormal (pathologic) conditions are corrected.
POST-RESUSCITATION INJURY
Injury to the major organs can continue unabated following apparently successful resuscitation of hypovolemic shock. This postresuscitation injury can be progressive and can involve several organs (the brain and intestinal tract appear to be most susceptible). Two processes have been implicated in the pathogenesis of this disorder: the no-reflow phenomenon and reperfusion injury.
No-Reflow Phenomenon
Defects in microvascular perfusion can persist despite the resuscitation of hypovolemic shock to premorbid levels of blood pressure and cardiac output. Several mechanisms have been proposed for this phenomenon, including calcium-induced vasoconstriction, leukocyte plugging, and vascular compression from the accumulation of edema fluid. Persistent hypoperfusion in the splanchnic circulation can lead to translocation of intestinal pathogens and postresuscitation septicemia. At present, there is no therapy that prevents the no-reflow phenomenon. Because its occurrence and severity seem to be related to the duration of ischemia, prompt resuscitation should help to prevent this complication.
Reperfusion Injury
Postresuscitation injury is also attributed to toxic metabolites that accumulate during the period of ischemia and are washed away during reperfusion, causing damage to remote tissues. Toxic oxygen metabolites have been implicated in this process. Two potential sources of enhanced oxidant production are neutrophil activation and generation of superoxide radicals from the oxidation of hypoxanthine. Despite the proposed role of oxidant injury in the reperfusion period, preliminary studies using antioxidants to prevent this phenomenon have been disappointing.
