Bradley A. Boucher and G. Christopher Wood
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. List the most common etiologies of decreased intravascular volume in hypovolemic shock patients.
2. Describe the major hemodynamic and metabolic abnormalities that occur in patients with hypovolemic shock.
3. Describe the clinical presentation, including signs, symptoms, and laboratory test measurements, for the typical hypovolemic shock patient.
4. Prepare a treatment plan with clearly defined outcome criteria for a hypovolemic shock patient that includes both fluid management and other pharmacologic therapy.
5. Compare and contrast the relative advantages and disadvantages of crystalloids, colloids, and blood products in the treatment of hypovolemic shock.
6. Formulate a stepwise monitoring strategy for a hypovolemic shock patient.
KEY CONCEPTS
Hypovolemic shock occurs as a consequence of inadequate intravascular volume to meet the oxygen and metabolic needs of the body.
Protracted tissue hypoxia sets in motion a downward spiral of events leading to organ dysfunction and eventual failure if untreated.
The overarching goals in treating hypovolemic shock are to restore effective circulating blood volume, as well as managing its underlying cause, thereby reversing organ dysfunction and returning to homeostasis.
Three major therapeutic options are available to clinicians for restoring circulating blood volume: crystalloids (electrolyte-based solutions), colloids (large-molecular-weight solutions), and blood products.
In the absence of ongoing blood loss, administration of 2,000 to 4,000 mL (about 4 to 8 pints) of isotonic crystalloid will normally re-establish baseline vital signs in adult hypovolemic shock patients.
Colloid solutions administered are primarily confined to the intravascular space, in contrast to isotonic crystalloid solutions that distribute throughout the extracellular fluid space.
Blood products are indicated in adult hypovolemic shock patients who have sustained blood loss from hemorrhage exceeding 1,500 mL (about 3 pints).
Vasopressors may be warranted as a temporary measure in patients with profound hypotension or evidence of organ dysfunction in the early stages of shock.
Major treatment goals in hypovolemic shock following fluid resuscitation are as follows: arterial systolic blood pressure (SBP) greater than 90 mm Hg within 1 hour, organ dysfunction reversal, and normalization of laboratory measurements as rapidly as possible (less than 24 hours).
INTRODUCTION
The principal function of the circulatory system is to supply oxygen and vital metabolic compounds to cells throughout the body, as well as removal of metabolic waste products. Circulatory shock is a life-threatening condition whereby this principal function is compromised. When circulatory shock is caused by a severe loss of blood volume or body water it is called hypovolemic shock, which is the focus of this chapter. Regardless of etiology, the most distinctive manifestations of hypovolemic shock are arterial hypotension and metabolic acidosis. Metabolic acidosis is a consequence of an accumulation of lactic acid resulting from tissue hypoxia and anaerobic metabolism. If the decrease in arterial blood pressure (BP) is severe and protracted, such hypotension will inevitably lead to severe hypoperfusion and organ dysfunction. Rapid and effective restoration of circulatory homeostasis through the use of fluids, pharmacologic agents, and/or blood products is imperative to prevent complications of untreated shock and ultimately death.
ETIOLOGY AND EPIDEMIOLOGY
Practitioners must have a good understanding of cardiovascular physiology to diagnose, treat, and monitor circulatory problems in critically ill patients. The interrelationships between the major hemodynamic variables are depicted in Figure 13–1.1 These variables include: arterial BP, cardiac output (CO), systemic vascular resistance (SVR), heart rate (HR), stroke volume (SV), left ventricular size, afterload, myocardial contractility, and preload. While an oversimplification, Figure 13–1 is beneficial in conceptualizing where the major abnormalities occur in patients with circulatory shock as well as predicting the body’s compensatory responses.
Shock can be effectively categorized by etiology into four major types: hypovolemic, obstructive, cardiogenic, and distributive (Table 13–1).2,3 As noted, all patients with shock have profound decreases in arterial BP. Understanding the primary cause of the circulatory abnormality in these respective shock states is invaluable to their management. Hypovolemic shock is caused by a loss of intravascular volume either by hemorrhage or fluid loss (e.g., dehydration). Obstructive shock is caused by an obstruction that directly compromises inflow or outflow of blood from the heart. Cardiogenic shock is caused by diminished myocardial contractility which results in decreased CO with an increase in SVR. Lastly, distributive shock is caused by a major decrease in SVR with an increase in CO. Differentiating between the underlying abnormality and the associated compensatory response is also essential in terms of treatment and monitoring. Hypovolemic shock is considered to be essentially a profound deficit in preload. Preload is defined as the volume in the left ventricle at the end of diastole. Decreased preload results in subsequent decreases in SV, CO, and eventually, mean arterial pressure (MAP). As such, restoration of preload becomes an over-riding goal in the management of hypovolemic shock.
The prognosis of shock patients depends on several variables including severity, duration, underlying etiology, pre-existing organ dysfunction, and reversibility.4 Data are not readily available as to the incidence of hypovolemic shock, although hypovolemia due to hemorrhage is a major factor in 40% to 50% of trauma deaths annually.5
FIGURE 13–1. Hemodynamic relationships among key cardiovascular parameters (A). Solid lines represent a direct relationship; the broken line represents an inverse relationship. In B, the alterations typically observed in hypovolemic shock are highlighted with arrows depicting the likely direction of the alteration. (From Ref. 1.)
Table 13–1 Major Shock Classifications and Etiologies
|
I. Hypovolemic |
|
Hernorrhagic |
|
Trauma |
|
Gl |
|
Abdominal aortic aneurysm |
|
Nonhemorrhagic (dehydration) |
|
Vomiting |
|
Diarrhea |
|
Third spacing |
|
II. Cardiogenic |
|
Myocardial infarction |
|
Septal wall rupture |
|
Acute mitral valve regurgitation |
|
Myocarditis |
|
Arrhythmias |
|
III. Obstructive |
|
Pericardial tamponade |
|
Pulmonary embolism |
|
Amniotic fluid embolism |
|
Tumor embolism |
|
IV. Distributive |
|
Sepsis |
|
Anaphylactic |
|
Spinal cord injury |
From Refs. 2, 3.
PATHOPHYSIOLOGY
The total amount of water in a typical 70 kg (154 lb) adult is approximately 42 L (Fig. 13–2). About 28 of the 42 L are inside the cells of the body (intracellular fluid) while the remaining 14 L are in the extracellular fluid space (fluid outside of cells: interstitial fluid and plasma). Circulating blood volume for a normal adult is roughly 5 L (70 mL/kg) and is comprised of 2 L of red blood cell fluid (intracellular) and 3 L of plasma (extracellular). By definition, hypovolemic shock occurs as a consequence of inadequate intravascular volume to meet the oxygen and metabolic needs of the body.Diminished intravascular volume can result from severe external or internal bleeding, profound fluid losses from GI sources such as diarrhea or vomiting, or urinary losses such as diuretic use, diabetic ketoacidosis, or diabetes insipidus (Table 13–1).3 Other sources of intravascular fluid loss can occur through damaged skin, as seen with burns, or via “capillary leak” into the interstitial space or peritoneal cavity, as seen with edema or ascites. This latter phenomenon is often referred to as “third spacing” since fluid accumulates in the interstitial space disproportionately to the intracellular and extracellular fluid spaces. Regional ischemia may also develop as blood flow is naturally shunted from organs such as the GI tract or the kidneys to more immediately vital organs such as the heart and brain.
FIGURE 13–2. Distribution of body fluids showing the extracellular fluid volume, intracellular body fluid volume, and total body fluids in a 70 kg (154 lb) adult. Extracellular volume (ECV) comprises 14 L of total body fluid (42 L). Plasma volume makes up approximately 3 L of the 14 L of ECV. Intracellular volume accounts for the remaining 28 L of total body fluids with roughly 2 L being located within the red blood cells. Blood volume (approximately 5 L) is also depicted and is made up of primarily red blood cells and plasma. (From Guyton AC, Hall JE. Textbook of Medical Physiology. 8th ed. Philadelphia: Saunders, 1991: 275, with permission.)
Hypovolemic shock symptoms begin to occur with decreases in intravascular volume in excess of 750 mL or 15% of the circulating blood volume (20 mL/kg in pediatric patients).6 As previously stated, decreases in preload or left ventricular end-diastolic volumes result in decreases in SV. Initially, CO may be partially maintained by compensatory tachycardia. Similarly, reflex increases in SVR and myocardial contractility may diminish arterial hypotension. This neurohumoral response to hypovolemia is mediated by the sympathetic nervous system in an attempt to preserve perfusion to vital organs such as the heart and brain (Fig. 13–3). Two major endpoints of this response are to conserve water to maximize intravascular volume and to improve tissue perfusion by increasing BP and CO (oxygen delivery). The body attempts to maximize its fluid status by decreasing water and sodium excretion through release of ADH, aldosterone, and cortisol. BP is maintained by peripheral vasoconstriction mediated by catecholamine release and the renin-angiotensin system.5 CO is augmented by catecholamine release and fluid retention.3,7However, when intravascular volume losses exceed 1,500 mL (about 3 pints), the compensatory mechanisms are inadequate, typically resulting in a fall in CO and arterial BP, while acute losses greater than 2,000 mL (about 4 pints) are life-threatening (35 mL/kg in pediatric patients).7 The decrease in CO results in a diminished delivery of oxygen to tissues within the body and activation of an acute inflammatory response.5 Oxygen delivery can be further compromised by inadequate blood hemoglobin levels due to hemorrhage and/or diminished hemoglobin saturation due to impaired ventilation. Decreased delivery of oxygen and other vital nutrients results in diminished production of the energy substrate, adenosine triphosphate (ATP). Lactic acid is then produced as a by-product of anaerobic metabolism within tissues throughout the body.3 Hyperglycemia produced during the stress response from cortisol release is also a contributing factor in the development of lactic acidosis. Lactic acidosis indicates that inadequate tissue perfusion has occurred.3 Protracted tissue hypoxia sets in motion a downward spiral of events leading to organ dysfunction and eventual failure if untreated.6 Table 13–2 describes the effects of shock on the body’s major organs. Relative failure of more than one organ, regardless of etiology, is referred to as the multiple organ dysfunction syndrome (MODS). Involvement of the heart is particularly devastating considering the central role it plays in oxygen delivery and the potential for myocardial dysfunction to perpetuate the shock state. Pre-existing organ dysfunction and build up of inflammatory mediators can also exacerbate the effects of hypovolemic shock to the point of irreversibility.5 For example, acute or chronic heart failure can lead to pulmonary edema, further aggravating gas exchange in the lungs and, ultimately, tissue hypoxia. MODS develops in approximately 20% of trauma patients who require fluid resuscitation. Only about one-third of early-onset MODS is quickly reversible (within 48 hours) with proper fluid resuscitation. Thus, it is imperative that hypovolemic shock be treated quickly to avoid MODS.8
FIGURE 13–3. Expected neurohumoural response to hypovolemia. (ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; Na, sodium.) (From Jimenez EJ. Shock. In: Civetta JM, Taylor RW, Kirby RR, eds. Critical Care. New York: Lippincott-Raven; 1997: 369, with permission.)
Table 13–2 Shock Manifestations on Major Organs
|
Heart |
|
• Myocardial ischemia |
|
• Dysrhythmias Brain |
|
• Restlessness, confusion, obtundation |
|
• Global cerebral ischemia Liver |
|
• Release of liver enzymes |
|
• Biliary stasis Lungs |
|
• Pulmonary edema. |
|
• ARDS |
|
Kidneys |
|
• Oliguria |
|
• Decreased glomerular filtration |
|
• Acute kidney injury |
|
• Gl tract |
|
• Stress-related mucosal disease |
|
• Bacterial translocation |
|
• Hematologic |
|
• Thrombocytopenia |
|
• Coagulopathies |
ARDS, acute respiratory distress syndrome; Gl, gastrointestinal.
Clinical Presentation and Diagnosis of Hypovolemic Shock
General
Patients will be in acute distress, although symptoms and signs will vary depending on the severity of the hypovolemia and whether the etiology is hemorrhagic versus nonhemorrhagic.
Symptoms
• Thirst
• Weakness
• Lightheadedness
Signs
• Hypotension, arterial systolic BP (SBP) less than 90 mm Hg or fall in SBP greater than 40 mm Hg
• Tachycardia
• Tachypnea
• Hypothermia
• Oliguria
• Dark, yellow-colored urine
• Skin color: pale to ashen; may be cyanotic in severe cases
• Skin temperature: cool to cold
• Mental status: confusion to coma
• Pulmonary artery catheter measurements: decreased CO, decreased SV, increased SVR, low pulmonary artery occlusion pressure (PAOP)
Laboratory Tests
• Hypernatremia
• Elevated serum creatinine
• Elevated blood urea nitrogen
• Decreased hemoglobin/hematocrit (hemorrhagic hypovolemic shock)
• Hyperglycemia
• Increased serum lactate
• Decreased arterial pH
Patient Encounter, Part 1
JT is a 65-year-old male admitted to the emergency department (ED) after a 3-day history of severe vomiting and diarrhea. The patient’s wife states that a “stomach virus” causing vomiting and diarrhea has been recently affecting several family members. JT is weak and confused, his breathing is labored, and he is losing consciousness. The initial diagnosis by the ED team is hypovolemic shock. A physical exam is being performed and blood samples are being sent to the laboratory.
What type of hypovolemic shock does JThave and what is the cause?
What signs and symptoms would you expect to see in this patient with hypovolemic shock?
What laboratory abnormalities might be expected in this patient?
What are the first nonpharmacologic steps in treating the patient?
TREATMENT
Desired Outcomes
The overarching goals in treating hypovolemic shock are to restore effective circulating blood volume, as well as manage its underlying cause. In achieving this goal, the downward spiral of events that can perpetuate severe or protracted hypovolemic shock is interrupted. This is accomplished through the delivery of adequate oxygen and metabolic substrates such as glucose and electrolytes to the tissues throughout the body that will optimally bring about a restoration of organ function and return to homeostasis. Evidence of the latter is a return to the patient’s baseline vital signs, relative normalization of laboratory test results, and alleviation of the other signs and symptoms of hypovolemic shock previously discussed.9 Concurrent supportive therapies are also warranted to avoid exacerbation of organ dysfunction associated with the hypovolemic shock event.
General Approach to Therapy
Securing an adequate airway and ventilation is imperative in hypovolemic shock patients consistent with the airway, breathing, and circulation (ABCs) of life support. Any compromise in ventilation will only accentuate the tissue hypoxia occurring secondary to inadequate perfusion. Thus, tracheal intubation and mechanical ventilation may be needed (Fig. 13–4). IV access is also essential for administration of IV fluids and medications. IV access can be accomplished through the placement of peripheral IV lines or catheterization with central venous lines if rapid or large volumes of resuscitative fluids are indicated. While primarily facilitating fluid administration, the IV lines provide access for blood samples for obtaining appropriate laboratory tests. Placement of an arterial catheter is advantageous to allow for accurate and continual monitoring of BP, as well as arterial blood gas (ABG) sampling. A bladder catheter should be inserted for ongoing monitoring of urine output. Baseline laboratory tests that should be done immediately include: complete blood cell counts with differentials, serum chemistry profile, liver enzymes, prothrombin and partial thromboplastin times, and serum lactate. A urinalysis and an ABG should also be obtained and ongoing ECG monitoring should be performed. In addition to restoring circulating blood volume, it is necessary to prevent further losses from the vascular space. This is especially true with hemorrhagic hypovolemic shock where identifying the bleeding site and achievement of hemostasis are critical in the successful resuscitation of the patient. This frequently involves surgical treatment of hemorrhages.
FIGURE 13–4. Treatment algorithm for the management of moderate to severe hypovolemia. (CVP, central venous pressure; MAP, mean arterial pressure; PA, pulmonary artery; PAOP, pulmonary artery occlusion pressure; PRBCs, packed red blood cells; SBP, systolic blood pressure.)
Upon stabilization, placement of a pulmonary artery (PA) catheter may be indicated based on the need for more extensive cardiovascular monitoring than is available from noninvasive measurements such as vital signs, cardiac rhythm, and urine output.9,10 Key measured parameters that can be obtained from a PA catheter are the pulmonary artery occlusion pressure (PAOP), which is a measure of preload, and CO. From these values and simultaneous measurement of HR and BP, one can calculate the left ventricular SV and SVR.10 Placement of a PA catheter should be reserved for patients at high risk of death due to the severity of shock or pre-existing medical conditions such as heart failure.11 Use of PA catheters in broad populations of critically ill patients is somewhat controversial because clinical trials have not shown consistent benefits with their use.12–14 However, critically ill patients with a high severity of illness may have improved outcomes from PA catheter placement. It is not clear why this was seen, but it could be that more severely ill patients have less physiologic reserve and less “room for error” and benefit from the therapeutic decisions that come from detailed PA catheter data.15 An alternative to the PA catheter is placement of a central venous catheter that typically resides in the superior vena cava to monitor central venous pressure (CVP). While central venous catheters are less expensive and more readily placed, they are not particularly accurate in monitoring effective fluid resuscitation.10
Fluid Therapy
Three major therapeutic options are available to clinicians for restoring circulating blood volume: crystalloids (electrolyte-based solutions), colloids (large-molecular-weight solutions), and blood products. Blood products are used only in instances involving hemorrhage (or severe preexisting anemia), thus leaving crystalloids and colloids as the mainstay of therapy in all types of hypovolemic shock, along with adjunctive vasopressor support. The aggressiveness of fluid resuscitation (rate and volume) will be dictated by the severity of the hypovolemic shock and the underlying cause. Warming of all fluids to 37°C (98.6°F) prior to administration is an important consideration to prevent hypothermia, arrhythmias, and coagulopathy, as they will have a negative impact on the success of the resuscitation effort.16
Crystalloids
Conventional, “balanced” crystalloids are fluids with (a) electrolyte composition that approximates plasma, such as lactated Ringer’s (LR), or (b) a total calculated osmolality similar to that of plasma (280 to 295 mOsm/kg), such as 0.9% sodium chloride (also known as normal saline [NS] or 0.9% NaCl) (Table 13–3).17 Thus, conventional crystalloids will distribute in normal proportions throughout the extracellular fluid space upon administration. In other words, expansion of the intravascular space will only increase by roughly 200 to 250 mL for every liter of isotonic crystalloid fluid administered.5Hypertonie crystalloid solutions such as 3% NaCl or 7.5% NaCl have osmolalities substantially higher than plasma. The effect observed with these fluids is a relatively larger volume expansion of the intravascular space. By comparison to conventional crystalloids, administration of 250 mL of 7.5% sodium chloride will result in an intravascular space increase of 500 mL.5 This increase is a result of the fluid administered as well as osmotic drawing of intracellular fluid into the intravascular and interstitial spaces. This occurs because the hypertonic saline increases the osmolality of the intravascular and interstitial fluid compared to the intracellular fluid. Hypertonic saline also has the potential for decreasing the inflammatory response.18 Despite these theoretical advantages, data are lacking demonstrating superiority of hypertonic crystalloid solutions compared with isotonic solutions.19 Crystalloids are generally advocated as the initial resuscitation fluid in hypovolemic shock because of their availability, low cost, and equivalent outcomes compared with colloids.9 A reasonable initial volume of an isotonic crystalloid (0.9% NaCl or LR) in adult patients is 1,000 to 2,000 mL (about 2 to 4 pints) administered over the first hour of therapy. Ongoing external or internal bleeding will require more aggressive fluid resuscitation. In the absence of ongoing blood loss, administration of 2,000 to 4,000 mL (about 4 to 8 pints) of isotonic crystalloid will normally re-establish baseline vital signs in adult hypovolemic shock patients.20 Selected populations, such as burn patients, may require more aggressive fluid resuscitation, while other patient subsets such as those with cardiogenic shock or heart failure may warrant less aggressive fluid administration to avoid over-resuscitation.21 In hemorrhagic shock patients, approximately three to four times the shed blood volume of isotonic crystalloids is needed for effective resuscitation.20,21
Side effects from crystalloids primarily involve fluid overload and electrolyte disturbances of sodium, potassium, and chloride.22 Dilution of coagulation factors can also occur resulting in a dilutional coagulopathy.5 Two clinically significant reasons LR is different from NS is that LR contains potassium and has a lower sodium content (130 versus 154 mEq/L or mmol/L). Thus, LR has a greater potential than NS to cause hyponatremia and/or hyperkalemia. Alternatively, NS can cause hypernatremia and hypokalemia. Nevertheless, there is no clear cut advantage when comparing NS and LR.
Colloids
Understanding the effects of colloid administration on circulating blood volume necessitates a review of those physiologic forces that determine fluid movement between capillaries and the interstitial space throughout the circulation (Fig. 13–5).5–23 Relative hydrostatic pressure between the capillary lumen and the interstitial space is one of the major determinants of net fluid flow into or out of the circulation. The other major determinant is the relative colloid osmotic pressure between the two spaces. Administration of exogenous colloids results in an increase in the intravascular colloid osmotic pressure. The effects of colloids on intravascular volume are a consequence of their relatively large molecular size (greater than 30 kilodaltons [kDa]), limiting their passage across the capillary membrane in large amounts. Alternatively stated, colloids can be thought of as “sponges” drawing fluid into the intravascular space from the interstitial space. In the case of isosmotic colloids (5% albumin, 6% hetastarch, and dextran products), initial expansion of the intravascular space is essentially 65% to 75% of the volume of colloid administered accounting for some “leakage” of the colloid from the intravascular space.5 Thus, in contrast to isotonic crystalloid solutions that distribute throughout the extracellular fluid space, the volume of isooncotic colloids administered remains relatively confined to the intravascular space. In the case of hyperoncotic solutions such as 25% albumin, fluid is pulled from the interstitial space into the vasculature resulting in an increase in the intravascular volume that is much greater than the original volume of the 25% albumin that was administered. While theoretically attractive, hyperoncotic solutions should not be used for hypovolemic shock since the expansion of the intravascular space is at the expense of depletion of the interstitial space. Exogenous colloids available in the United States include 5% albumin, 25% albumin, 5% plasma protein fraction (PPF), 6% hetastarch, 10% pentastarch, 10% dextran 40, 6% dextran 70, and 6% dextran 75 (Table 13-3). The first three products are derived from pooled human plasma. Hetastarch and pentastarch are semisynthetic hydroxyethyl starches derived from amylopectin. The dextran products are semisynthetic glucose polymers that vary in terms of the average molecular weight of the polymers. Superiority of one colloid solution over another has not been clearly established.24
Table 13–3 Composition of Common Resuscitation Fluids
FIGURE 13–5 Operative forces at the capillary membrane tend to move fluid either outward or inward through the capillary membrane. In hypovolemic shock, one therapeutic strategy is the administration of colloids that can sustain and/or draw fluid from the interstitial space by increasing the plasma colloid osmotic pressure. (From Guyton AC, Hall JE. Textbook of Medical Physiology. 8th ed. Philadelphia: Saunders; 1991: 174, with permission.)
For years within the critical care literature a controversy known as the “colloid versus crystalloid debate” raged over the relative merits of the two types of resuscitation fluids. At the center of the debate was what the goal of fluid resuscitation in shock should be: immediate expansion of the intravascular space with colloids versus expansion of the entire extracellular fluid space with crystalloids. A randomized controlled study involving 6,997 critically ill patients (Saline versus Albumin Fluid Evaluation [SAFE] study) demonstrated no difference in mortality between patients receiving saline versus albumin.25Largely in response to the SAFE trial, the FDA issued a notice to health care providers in May 2005 declaring albumin safe for use in most critically ill patients.26 Burn, traumatic brain injury, and septic shock patients were excluded from the SAFE trial; however, based on previous data there do not appear to be a clear-cut overall advantage for either crystalloids or colloids in these patient groups.26 Thus, while the debate is not fully resolved, most clinicians today prefer using crystalloids based on their availability and inexpensive cost compared with colloids.21,27
Generally, the major adverse effects associated with colloids are fluid overload, dilutional coagulopathy, and anaphylactoid/anaphylactic reactions.28,29 Although derived from pooled human plasma, there is no risk of disease transmission from commercially available albumin or PPF products since they are heated and sterilized by ultrafiltration prior to distribution.28 Because of direct effects on the coagulation system with the hydroxyethyl starch and dextran products, they should be used cautiously in hemorrhagic shock patients. This is another reason why crystalloids may be preferred in hemorrhagic shock. Furthermore, hetastarch can result in an increase in amylase not associated with pancreatitis. As such, the adverse-effect profiles of the various fluid types should also be considered when selecting a resuscitation fluid.
Blood Products
Blood products are indicated in hypovolemic shock patients who have sustained blood losses from hemorrhage exceeding 1,500 mL. This, in fact, is the only setting in which freshly procured whole blood is administered. In virtually all other settings, blood products are given as the individual components of whole blood units, such as packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate, and concentrated coagulation factors.30 This includes ongoing resuscitation of hemorrhagic shock, when PRBCs can be transfused to increase oxygen-carrying capacity in concert with crystalloid solutions to increase blood volume. In patients with documented coagulopathies, FFP for global replacement of lost or diluted clotting factors, or platelets for patients with severe thrombocytopenia (less than 20 × 10/mm3 or 20 × 109L]) should be administered.31 Type O negative blood or “universal donor blood” is given in emergent cases of hemorrhagic shock. Thereafter, blood that has been typed and cross-matched with the recipient’s blood is given. The traditional threshold for PRBC transfusion in hypovolemic shock has been a serum hemoglobin of less than 10 g/dL (100 g/L or 6.2 mmol/L) and hematocrit less than 30%. However, a more restrictive transfusion threshold of 7 g/dL (70 g/L or 4.34 mmol/L) appears to be safe for critically ill patients after they have received appropriate fluid resuscitation and have no signs of ongoing bleeding.32 Traditional risks from allogeneic blood product administration include hemolytic and nonhemolytic transfusion reactions and transmission of bloodborne infections in contaminated blood. However, recent large studies have also shown that transfusions are associated with higher mortality, possibly because of adverse immune and inflammatory effects.30Based on limitations of homologous blood donations, intraoperative salvage techniques can be employed in patients with massive hemorrhage in an effort to conserve blood.6,32,33
Due to blood shortages and associated risks with transfusions, there are ongoing research efforts concerning the development of red blood cell substitutes as a possible therapy alternative. Products that have reached clinical trials include perfluorocarbon emulsions and hemoglobin-based oxygen carriers (HBOCs).34 These blood products have several advantages over PRBCs including greater availability (because donors aren’t needed), increased shelf-life, absence of infectious risks, and no need for cross-matching. As such, red blood cell substitutes have the potential to serve as temporizing measures in hypovolemic shock patients until conventional red blood cell transfusions can be administered or in instances in which availability of donated PRBCs is extremely limited. Nonetheless, lack of adequate efficacy data and additional side effects associated with each of the respective red blood cell substitutes have precluded their approval in the United States at present.34
Research also continues into the use of recombinant activated factor VII (rFVIIa) as an adjunctive agent to treat uncontrolled hemorrhage. Initial experiences with rFVIIa show that it can decrease transfusions, though large studies have not been performed.35 A major unresolved issue surrounding the use of rFVIIa is its safety where the risk of thromboembolic events in patients receiving this agent off-label was recently highlighted.36 The optimal dose of rFVIIa in nonhemophilic patients is also unknown. This latter issue is particularly important in light of the high acquisition costs for rFVIIa, and ultimately, pharmacoeconomic analyses of rFVIIa will be needed.
Pharmacologic Therapy
Vasopressor Therapy
Vasopressor is the term used to describe any pharmacologic agent that can induce arterial vasoconstriction through stimulation of the α1-adrenergic receptors. While replenishment of intravascular volume is undoubtedly the cornerstone of hypovolemic shock therapy, use of vasopressors may be warranted as a temporary measure in patients with profound hypotension or evidence of organ dysfunction in the early stages of shock.2,9 Typically, vasopressors are used concurrently with fluid administration. Table 13–4 is a list of those vasopressors used in the management of hypovolemic shock. Dopamine or norepinephrine may be preferred over epinephrine because epinephrine has an increased potential for causing cardiac arrhythmias and impaired abdominal organ (splanchnic) circulation.37 In cases involving concurrent heart failure, an inotropic agent such as dobutamine may be needed, in addition to the use of a vasopressor.
Vasopressors are almost exclusively administered as continuous infusions because of their very short duration of action and the need for close titration of their dose-related effects. Starting doses should be at the lower end of the dosing range followed by rapid titration upward if needed to maintain adequate BP. Monitoring of end-organ function such as adequate urine output should also be used to monitor therapy. Once BP is restored, vasopressors should be weaned and discontinued as soon as possible to avoid any untoward events. The most significant systemic adverse events associated with vasopressors are excessive vasoconstriction resulting in decreased organ perfusion and potential to induce arrhythmias (Table 13–4). Central venous catheters should be used to minimize the risk of local tissue necrosis that can occur with extravasation of peripheral IV catheters.
Supportive Care Measures
Lactic acidosis, which typically accompanies hypovolemic shock as a consequence of tissue hypoxia, is best treated by reversal of the underlying cause. Administration of alkalizing agents such as sodium bicarbonate has not been demonstrated to have any beneficial effects and may actually worsen intracellular acidosis.38 Since GI ischemia is a common complication of hypovolemic shock, prevention of stress-related mucosal disease should be instituted as soon as the patient is stabilized. The most common agents used for stress ulcer prophylaxis are the histamine2-receptor antagonists and proton pump inhibitors. Prevention of thromboembolic events is another secondary consideration in hypovolemic shock patients. This can be accomplished with the use of external devices such as sequential compression devices and/or antithrombotic therapy such as the low-molecular-weight heparin products or unfraction-ated heparin. Patients with adrenal insufficiency due to pre-existing disease, glucocorticoid use, or critical illness may have refractory hypotension despite resuscitation. Such patients should receive appropriate glucocorticoid replacement therapy (e.g., hydrocortisone).
Patient Encounter, Part 2: Physical Exam, Diagnostic Tests, and Initial Treatment
PMH: Hypertension, congestive heart failure
Meds: Benazepril 10 mg daily, atenolol 50 mg daily, furosemide 40 mg daily as needed for edema
SH: Occasional alcohol use (per family)
FH: Noncontributory
PE: Ht 5’9” (175 cm), Wt 65 kg (143 lb)
VS: 80/40 mm Hg, P 130 bpm, RR 22, T 35.0°C (95.0°F), urine output: none since catheterization 10 minutes ago
Neuro: Recent loss of consciousness
Pulmonary: Normal breath sounds, undergoing tracheal intubation for mechanical ventilation
CV: ECG shows sinus tachycardia, otherwise normal
Abd: WNL
Extremities: Noncontributory
Pertinent labs: pH 7.20, PaCO2 50 mm Hg (6.65 kPa), PaO2 70 mm Hg (9.31 kPa), Na 153 mEq/L (153 mmol/L), HCO3 18 mEq/L (18 mmol/L), lactate 70 mg/dL (0.78 mmol/L), SCr 1.7 mg/dL (150 μmol/L), Hct 51%
Identify treatment goals for JT in the next hour.
Identify treatment goals for JT in the next 24 hours.
What initial pharmacologic/fluid therapy is required?
Comment on the need for blood products or sodium bicarbonate in JT.
Table 13–4 Vasopressor Drugs
OUTCOME EVALUATION
Successful treatment of hypovolemic shock is measured by the restoration of BP to baseline values and reversal of associated organ dysfunction. The likelihood of a successful fluid resuscitation will be directly related to the expediency of treatment. Therapy goals include:
• Arterial SBP greater than 90 mm Hg (MAP greater than 60 mm Hg) within 1 hour
• Organ dysfunction reversal evident by increased urine output to greater than 0.5 mL/kg/h (1.0 mL/kg/h in pediatrics), return of mental status to baseline, and normalization of skin color and temperature over the first 24 hours
• HR should begin to decrease reciprocally to increases in the intravascular volume within minutes to hours
Patient Encounter, Part 3: Care Plan/Ongoing Therapy
One hour after the initial fluid bolus, JT’s vital signs are:
BP 85/50 mm Hg, HR 120 bpm, RR 20, urine output: 15 mL in past hour. Pertinent new labs: lactate 4.8 mg/dL (0.53 mmol/L). JT has regained consciousness but is weak and confused.
What is your assessment of the patient’s condition compared to 1 hour ago?
What therapy is required at this time?
How does JT’s past medical history affect therapy decisions?
Describe monitoring over the next 24 hours.
Patient Care and Monitoring
1. Does the patient have an adequate airway and ventilation (hemoglobin saturation greater than 92%)? If not, trained emergency personnel should consider performing tracheal intubation with initiation of mechanical ventilation.
2. Is there a detectable BP? If yes, obtain history, perform physical examination, obtain blood for baseline laboratory tests, and monitor ECG. If not, begin isotonic crystalloid fluid resuscitation immediately (see step 4).
3. Monitor the following serial laboratories for comparison to baseline values every 6 hours in the first 24 hours and daily thereafter until normalized: sodium, serum creatinine, blood urea nitrogen, serum lactate, glucose, bilirubin, hemoglobin, hematocrit, platelets, prothrombin time, partial thromboplastin time, ABGs, and pH.
4. Is the systolic BP less than 90 mm Hg (MAP less than 60 mm Hg)? If yes, start aggressive fluid therapy beginning with 1,000 to 2,000 mL lactated Ringer’s over 1 hour in adults (20 mL/kg in pediatrics). Monitor BP at least every 15 minutes (or continuously via an arterial catheter).
5. Is the patient bleeding? If yes, transfuse 5 to 10 mL/kg PRBCs. (Note: 1 unit PRBCs will provide approximately 3% increase in hematocrit or 1 g/dL [10 g/L or 0.62 mmol/L] increase in hemoglobin.) Do not allow hemoglobin concentrations to fall below 7 g/dL (70 g/L or 4.34 mmol/L; hematocrit 20%). Conventional goal hemoglobin concentration is 10 g/dL (100 g/L or 6.2 mmol/L; alternatively, hematocrit greater than or equal to 30%). Provide emergent control of ongoing hemorrhaging.
6. Is there evidence of cerebral or myocardial ischemia? If yes, begin vasopressor therapy of dopamine 10 mcg/kg/min or norepineprhine 2 mcg/min. Titrate dosage every 5 minutes as needed. Wean and discontinue vasopressor as soon as the goal arterial BP has been achieved.
7. Has the goal arterial BP been achieved? If not, give additional fluid therapy hourly blending crystalloids and isooncotic colloids based on inadequate BP response.
8. Is the patient hemodynamically stable? If not, admit to the intensive care unit for ongoing treatment and monitoring. A PA catheter (or CVP catheter) should be inserted by trained medical personnel. Monitor PAOPto a goal pressure of 14 to 18 mm Hg and minimum cardiac index of 2.2 L/min/m2 (alternatively CVP 8 to 15 cm H2O).
9. Monitor normalization of organ function to baseline state including mental status, urine output to greater than 0.5 mL/kg/h (1 mL/kg/h in pediatric patients), normal skin color and temperature, and normalization of base deficit and/or lactate. Begin supportive care measures including stress ulcer prophylaxis and antithrombotic therapy if there is no evidence of ongoing bleeding.
10. Has the underlying cause of the hypovolemic shock been addressed to prevent its recurrence? If not, treat as necessary.
11. Is there any evidence of adverse events from the resuscitation therapies employed such as fluid overload, electrolyte disturbances, transfusion reactions, and/or alterations in coagulation? If yes, manage the particular adverse event accordingly.
• Normalization of laboratory measurements expected within hours to days following fluid resuscitation. Specifically, normalization of base deficit and serum lactate is recommended within 24 hours to potentially decrease mortality39 and
• Achievement of PAOP to a goal pressure of 14 to 18 mm Hg occurs (alternatively, CVP 8 to 15 mm Hg)
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
REFERENCES
1. Braunwald E. Regulation of the circulation. I. N Engl J Med 1974;290:1124–1129.
2. Astiz ME. Pathophysiology and classification of shock states. In: Fink MP, Abraham E, Vincent JL, et al., eds. Textbook of Critical Care. Philadelphia: Elsevier Saunders, 2005:897–904.
3. Jones AE, Kline JA. Shock. In: Marx JA, Hockberger RS, Walls RM. eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. Philadelphia: Mosby Elsevier, 2006:41–56.
4. Vallet B, Wiel E, Lebuffe G. Resuscitation from circulatory shock. In: Fink MP, Abraham E, Vincent JL, et al., eds. Textbook of Critical Care. Philadelphia: Elsevier Saunders, 2005:905–910.
5. Puyana JC. Resuscitation of hypovolemic shock. In: Fink MP, Abraham E, Vincent JL, et al., eds. Textbook of Critical Care. Philadelphia: Elsevier Saunders, 2006:1933-1943.
6. Stern SA, Bobke EMK. Resuscitation: Management of shock. In: Ferrera PC, Colucciello SA, Marx JA, et al., eds. Trauma Management: An Emergency Medicine Approach. St. Louis: Mosby, 2002:75-102.
7. Harbrecht BG, Alarcon LH, Peitzman AB. Management of shock. In: Moore EE, Feliciano DV, Mattox KL, eds. Trauma. New York: McGraw-Hill, 2004:201-226.
8. Ciesla DJ, Moore EE, Johnson JL, et al. Multiple organ dysfunction during resuscitation is not postinjury multiple organ failure. Arch Surg 2004;139:590-594.
9. Moore FA, McKinley BA, Moore EE. The next generation in shock resuscitation. Lancet 2004;36:1988-1996.
10. Rhodes A, Grounds RM, Bennett ED. Hemodynamic monitoring. In: Fink MP, Abraham E, Vincent JL, et al., eds. Textbook of Critical Care. Philadelphia: Elsevier Saunders, 2005:735-739.
11. Practice guidelines for pulmonary artery catheterization: An updated report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Anesthesiology 2003;99: 988-1014.
12. Ivanov R, Allen J, Calvin JE. The incidence of major morbidity in critically ill patients managed with pulmonary artery catheters: A meta-analysis. Crit Care Med 2000;28:615-619.
13. Richard C, Warszawski J, Anguel N, et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: A randomized controlled trial. JAMA 2003;290: 2713-2720.
14. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med 2003;348:5-14.
15. Chittock DR, Dhingra VK, Ronco JJ, et al. Severity of illness and risk of death associated with pulmonary artery catheter use. Crit Care Med 2004;32:911-915.
16. Hoffman GL. Blood and blood components. In: Marx JA, Hockberger RS, Walls RM. eds. Rosen’s Emergency Medicine. Concepts and Clinical Practice. Philadelphia: Mosby Elsevier, 2006:56-61.
17. Zaloga GP, Kirby RR, Bernards WC, et al. Fluids and electrolytes. In: Civetta JM, Taylor RW, Kirby RR, eds. Critical Care. New York: Lippincott-Raven, 1997:413-441.
18. Rhee P, Koustova E, Alam HB. Searching for the optimal resuscitation method: Recommendations for the initial fluid resuscitation of combat casualties. J Trauma 2003;54:S52-S62.
19. Bunn F, Roberts I, Tasker R, et al. Hypertonie versus near isotonic crystalloid for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2004:CD002045.
20. Mullins RJ. Management of shock. In: Mattox KL, Feliciano DV, Moore EE, eds. Trauma. New York: McGraw-Hill, 2000:195-232.
21. Shafi S, Kauder DR. Fluid resuscitation and blood replacement in patients with polytrauma. Clin Orthop Relat Res 2004:37-42.
22. Revell M, Greaves I, Porter K. Endpoints for fluid resuscitation in hemorrhagic shock. J Trauma 2003;54:S63-S67.
23. Guyton AC, Hall JE. Textbook of Medical Physiology. 10th ed. Philadelphia: Saunders, 2000.
24. Bunn F, Alderson P, Hawkins V. Colloid solutions for fluid resuscitation. Cochrane Database Syst Rev 2003:CD001319.
25. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-2256.
26. Safety of albumin administration in critically ill patients. Rockville, MD: U.S. Food and Drug Administration, 2005.
27. Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2007:CD000567.
28. Boldt J. Volume replacement in the surgical patient—Does the type of solution make a difference? Br J Anaesth 2000;84:783-793.
29. Barron ME, Wilkes MM, Navickis RJ. A systematic review of the comparative safety of colloids. Arch Surg 2004;139:552-563.
30. Boucher BA, Hannon TJ. Blood management: A primer for clinicians. Pharmacotherapy 2007;27:1394-1411.
31. Kelley DM. Hypovolemic shock: An overview. Crit Care Nurs Q 2005;28:2-19.
32. Mclntyre LA, Hebert PC. Can we safely restrict transfusion in trauma patients? Curr Opin Crit Care 2006;12:575-583.
33. Fowler RA, Berenson M. Blood conservation in the intensive care unit. Crit Care Med 2003;31:S715-S720.
34. Stollings JL, Oyen LJ. Oxygen therapeutics: Oxygen delivery without blood. Pharmacotherapy 2006;26:1453-1464.
35. Holcomb JB. Use of recombinant activated factor VII to treat the acquired coagulopathy of trauma. J Trauma 2005;58:1298-1303.
36. O’Connell KA, Wood JJ, Wise RP, et al. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA 2006;295:293-298.
37. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.
38. Boyd JH, Walley KR. Is there a role for sodium bicarbonate in treating lactic acidosis from shock? Curr Opin Crit Care 2008;14:379-383.
39. Tisherman SA, Barie P, Bokhari F, et al. Clinical practice guideline: Endpoints of resuscitation. J Trauma 2004;57:898-912.