Presenting Signs and Symptoms

Absolute hypovolemia occurs as a consequence of loss of water, electrolytes, or blood (or any combination of the three) (Box 159.1). Patients with hypovolemia most often have symptoms related to reduced cardiac output such as fatigue, dyspnea, postural dizziness, and near or true syncope. Tolerance is variable and depends on the acuity and severity of the hypovolemia, associated anemia, individual physiologic reserve, and primary cause. Organ dysfunction is often a heralding sign of hypovolemia and may occur in the absence of global hypoperfusion or frank hemodynamic instability.

Shock is defined as a state of inadequate tissue perfusion in which oxygen delivery does not meet metabolic requirements. The term does not reflect perfusion pressure—shock may occur with low, normal, or elevated blood pressure. Unfortunately, clinical signs are unreliable indicators of oxygen delivery and blood volume.^5,⁶

Compensated shock refers to inadequate perfusion in the setting of normal blood pressure. The majority of critically ill patients are in compensated shock. The difficulty in identifying these patients prompted the terms occult and cryptic shock to describe normotensive patients with alternative evidence of cardiovascular insufficiency. Hyperlactatemia (<3 mmol/L) is an important marker to aid in identification of these high-risk patients.⁷ Left unresuscitated, these patients often progress to frank hypotension.

Brief episodes of hypotension are important markers of hypoperfusion and herald progressive hemodynamic deterioration. These self-limited episodes of transient hypotension represent progressive exhaustion of cardiovascular compensation and are the first sign of uncompensated shock.⁸ Uncompensated shock is characterized by hypotension that occurs when physiologic attempts to maintain normal perfusion pressure are overwhelmed or exhausted. Sustained hypotension signifies a late stage of shock.

Volume status and perfusion should be evaluated during every emergency department (ED) examination (Box 159.2). Delayed capillary refill, dry axillae and mucous membranes, abnormal skin turgor, sunken eyes, and a depressed fontanelle are classic but imperfect hallmarks of hypovolemia.^9,¹⁰ Peripheral cyanosis, cool extremities, and cutaneous mottling (cutis marmorata) characterize classic hypodynamic shock but are not a primary indication of hypovolemia. In contrast, early hyperdynamic septic shock may be manifested as peripheral vasodilation with warm extremities and brisk capillary refill.

Generalized tissue edema reflects total body sodium and fluid excess but does not quantify intravascular status and may be accompanied by hypovolemia, especially in acute illness. Acute weight change implies loss of fluid rather than lean body mass and is helpful in patients with a reliable comparison weight.

Treatment

Circulatory failure is the final common pathway of many diseases. Inadequate circulating volume is the most common and immediately reversible factor in patients with acute circulatory insufficiency. Accordingly, fluid therapy is the initial management of undifferentiated shock. Pathologic vasodilation compounds the fluid deficit in common conditions such as sepsis, anaphylaxis, adrenal failure, neurogenic shock, and toxin-induced shock. Acute cardiac decompensation and pulmonary embolism are two exceptional situations in which limited volume resuscitation takes secondary priority to catecholamine and mechanical support.

Early recognition of hypovolemia and shock must be coupled with aggressive resuscitation to have an effect on patients. Timely resuscitation is important because the window to reverse critical organ hypoperfusion and affect clinical outcome is measured in hours and often transpires in the ED.¹¹ Equivalent but delayed resuscitation yields greater morbidity and mortality.¹²^–¹⁵ The immediate goal of fluid resuscitation is intravascular expansion to optimize stroke volume and oxygen delivery.

Fluid Resuscitation

Resuscitation Targets (End Points)

The target end point of resuscitation guides the dose and selection of interventions, including fluid therapy. In high-risk patients, fluid selection appears to be less important than volume dosage titrated to an appropriate therapeutic end point.^1,¹⁶ Rapid restoration of systemic pressure (mean arterial pressure > 65 mm Hg) is a first priority to support vital organ autoregulated blood flow. However, stabilization of blood pressure does not guarantee adequate organ perfusion—resuscitation aimed primarily at normotension risks leaving the patient in persistent compensated shock.¹⁷ Unfortunately, there is no single best resuscitation end point for all clinical circumstances. An approach seeking to normalize a combination of both global and regional perfusion markers is most prudent (Box 159.3).

Empiric Fluid Challenge

Empiric volume challenges remain the standard means of early fluid resuscitation. Volume expansion is achieved by infusing serial aliquots of isotonic fluid under direct observation. This strategy is appropriate for acute undifferentiated shock or for obvious or suspected hypovolemia. Crystalloid (10 to 20 mL/kg) or colloid (4 to 7 mL/kg) should be infused rapidly over a period of 15 minutes with serial boluses titrated to the clinical end point objective while monitoring for adverse effects. A positive clinical response to volume loading confirms volume responsiveness but does not predict further response to therapy. Failure to recognize patients not responding to fluid may contribute to overly aggressive volume therapy and delay alternative care measures.

Total volume requirements are difficult to predict at the onset of resuscitation and are often underestimated. Classic hypovolemia, as occurs with acute hemorrhage or fluid loss, may stabilize rapidly with appropriate volume expansion. The 3 : 1 rule of hemorrhage resuscitation suggests that 3 volumetric units of crystalloid are required to replete an extracellular fluid deficit of 1 unit of blood loss. However, experimental models have confirmed that with severe hemorrhage, volume requirements exceed the 3 : 1 suggestion. Pathologic vasodilation and capillary leak contribute to the need for ongoing volume replacement. Exaggerated transcapillary fluid shifts are common with early burns, peritonitis, and pancreatitis. Crystalloid requirements average greater than 60 mL/kg in the first hours of septic shock but may be as high as 200 mL/kg to normalize perfusion.^18,¹⁹

Predicting Volume Responsiveness

The utility of fluid administration to improve stroke volume depends on a number of variables, including venous tone and ventricular function. Critically ill patients may manifest continued hypoperfusion despite initial empiric volume resuscitation. As an example, only half of hypotensive patients with sepsis are stabilized with volume resuscitation alone.¹⁹ In the absence of overt clinical hypovolemia or ongoing fluid loss, volume responsiveness should not be assumed. Continued fluid therapy does not have any impact on macrocirculatory flow in up to 50% of critically ill patients.²⁰

Volume or preload responsiveness refers to the ability to augment stroke volume with fluid administration. In contrast to an empiric volume challenge, volume responsiveness is gauged before fluid administration, and the resulting information is used to guide whether fluid administration is a solution to reverse clinical hypoperfusion. Fluid loading in volume-unresponsive patients is optimally avoided because it delays appropriate therapy and contributes to fluid excess that contributes to organ dysfunction, including hypoxemic respiratory failure and abdominal compartment syndrome.⁴ A more rational approach for patients who remain hypoperfused after initial empiric management incorporates selection and titration of subsequent therapy under the guidance of objective cardiovascular monitoring.

A target central venous pressure (CVP) of 8 to 12 mm Hg is recommended to maximize preload before instituting pressor and inotropic support.²¹ Unfortunately, there is no consistent threshold CVP to reliably estimate response to fluid administration.²² Values that are considered low, normal, or high can be found in patients who respond positively to fluid.²⁰

Dynamic hemodynamic indices are more dependable signs of volume responsiveness. Respirophasic variation in stroke volume during positive pressure mechanical ventilation is among the most useful signs of fluid responsiveness.²⁰ Respiratory collapse of the inferior vena cava (IVC) is another helpful indicator. Minimal IVC variation is associated with supranormal CVP and a low probability of fluid responsiveness. Inspiratory IVC collapse greater than 50% indicates a high probability of augmenting stroke volume with fluid therapy.

Fluid Selection

Early resuscitation and ongoing replacement of fluid deficits may be performed with a variety of fluids. Because each possesses specific benefits and potential disadvantages in given clinical scenarios, an understanding of fluid composition is important. Isotonic solutions are effective volume expanders (Table 159.2). Electrolyte disorders (including hypernatremia and hyponatremia) take secondary priority to isotonic volume loading in hypoperfused patients. Hypotonic solutions are ineffective and inappropriate volume expanders.

Table 159.2 Intravenous Fluid Composition and Distribution

Crystalloids

Isotonic sodium-based crystalloids are distributed to the extracellular compartment, which includes the vascular space. Partitioning within the extracellular fluid leaves 25% of the infused volume within the circulation. Normal saline and lactated Ringer (LR) solution are two isotonic resuscitation solutions in common use. LR solution, also known as Hartmann solution, was developed as a more physiologic alkalinizing replacement solution; bicarbonate is generated by lactate metabolism via the Cori cycle.

The clinical superiority of any single crystalloid remains unproved, and selection of fluid should be based on the source of the hypovolemia, associated electrolyte derangements, and volume requirements. Normal saline provides a supraphysiologic chloride load that induces metabolic acidosis when administered in large volumes. This is advantageous in correcting the volume and electrolyte disturbances (hypochloremic metabolic alkalosis) associated with loss of gastric secretions (e.g., profuse vomiting, gastric outlet obstruction, nasogastric suctioning). LR solution provides a more physiologic electrolyte balance and is often preferred for large-volume resuscitation. LR is recommended for trauma resuscitation but is incompatible with blood. Isotonic bicarbonate (i.e., three ampules of sodium bicarbonate in 1 L of sterile water) is an alternative resuscitation fluid for patients with coexisting metabolic acidosis.

Colloids

Colloid solutions are composed of electrolyte preparations reinforced with macromolecules designed to preserve colloid oncotic pressure. Vascular retention of colloid makes these formulations more efficient volume expanders with a longer duration of action than is the case with crystalloids. Crystalloid solutions require two to four times more volume for equivalent resuscitation. Dilutional hypoalbuminemia, transcapillary fluid shift, and interstitial and pulmonary edema may therefore be limited with colloid use. When dosed to the same end points, colloids and crystalloids are equally effective. Randomized clinical trials have failed to prove clinical superiority of one fluid class, with comparable rates of mortality and lung dysfunction.^23,²⁴ Traumatic brain injury remains one important exception in which isotonic albumin is associated with a higher risk for adverse outcomes when compared with equivalent crystalloid.^23,²⁵ Crystalloid solutions remain the standard ED choice for resuscitation and confer a significant cost advantage over colloid solutions.

Human albumin and hydroxyethyl starch (HES) are the colloids primarily used in clinical practice in the United States. Human albumin solutions are heat-sterilized derivatives of donor plasma. Isotonic 5% albumin is recommended for resuscitation of patients with severe hypoalbuminemia and end-stage liver disease, but there is little outcome evidence to support this position.^21,^26,²⁷ HES, a semisynthetic polymerized amylopectin compound, has supplanted dextran and gelatin-based colloids. A 6% solution provides volume expansion equivalent to that of 5% albumin. The renal dysfunction and coagulopathy that complicated early-generation synthetic colloids do not appear to be clinically significant with new-generation HES solutions.

Hypertonic Solutions

Hyperoncotic Albumin

Infusions of hyperoncotic albumin (20% to 25%) result in vascular expansion greater than two times the volume administered. Besides the obvious benefits of small-volume resuscitation, improved portability, and more rapid hemodynamic stabilization, hyperoncotic albumin has additional advantages. Synergistic interaction with administered drugs and primary antioxidant effects are explanations hypothesized for the improved morbidity linked to hyperoncotic albumin administrated to patients with complicated hypoalbuminemic states.²⁷ End-stage liver disease is one important example in which hyperoncotic albumin attenuates renal dysfunction and death in patients with spontaneous bacterial peritonitis or those undergoing large-volume paracentesis.²⁸^–³⁰

Hypertonic Saline

Hypertonic sodium solutions rapidly expand intravascular volume by mobilizing water from the interstitial and intracellular spaces. A small infusion expands plasma several times the volume infused. Used alone, the hemodynamic impact of hypertonic crystalloid is transient. Hypertonic crystalloid is often used in combination with hyperoncotic colloid (6% dextran or 10% HES) to sustain vascular expansion. Animal resuscitation models have demonstrated additional benefits, including enhanced cardiac output, improved microcirculatory flow, and attenuated inflammatory response. Hypertonic saline is safe, but data are insufficient to conclude that it is better than isotonic crystalloid for the resuscitation of patient with burns, trauma, or sepsis.³¹ Severely traumatized patients with associated traumatic brain injury remain an exceptional use for hypertonic saline, but outcome evidence is mixed.^32,³³

Special Treatment Considerations

Minimal-Volume Resuscitation of Hemorrhagic Shock

Traditional resuscitation of hemorrhagic shock prioritized rapid restoration of circulating blood volume with crystalloid and blood products. Strategic limited-volume resuscitation for uncontrolled hemorrhage dates back to the early 1900s and reemerged in the 1980s.

The rationale is that the increased intravascular pressure and hemodilution resulting from aggressive fluid resuscitation compounds the blood loss by precipitating rebleeding from hemostatic sites. Animal models of uncontrolled hemorrhage reveal that aggressive fluid administration reduces oxygen delivery and results in higher mortality. The widely recognized Houston experience showed a mortality benefit in penetrating trauma victims, but the results have yet to be matched by other investigators.^34,³⁵ In this strategy, hypotensive patients with a source of uncontrolled life-threatening hemorrhage receive IV fluids titrated to sustain critical organ flow until definitive surgical control is achieved (see Box 159.3). Conventional resuscitation ensues once surgical hemostasis is achieved.

The degree and duration of permissive hypotension remain to be clarified, although current recommendations target a systolic blood pressure of 70 mm Hg. Patients with concomitant traumatic brain injury are not candidates for this strategy.

Burn Resuscitation

Patients with partial-thickness and full-thickness burns exhibit marked fluid shifts related to denuded skin, injured tissue, and the systemic inflammatory response. Early anticipation of these large fluid requirements prevents underresuscitation. The Parkland formula remains the most commonly used guide for acute burn resuscitation. Formula calculations are based on the time of injury rather than the time until medical attention and incorporate prehospital fluid administration. All burn formulas provide only estimates of fluid requirements. The requirements must be modified and individualized based on patient response because volume needs may substantially exceed formula approximation.³⁶ LR solution is the resuscitation crystalloid preparation of choice for acute burn management. In addition to burn formula replacement, maintenance fluid requirements should be allocated. Urine output greater than 1 mL/kg/hr is a traditional end point of acute burn resuscitation and may be augmented by the perfusion end points discussed earlier.

Oral Rehydration Therapy

Oral rehydration therapy is a valuable tool for maintenance and correction of mild to moderate dehydration secondary to gastroenteritis in children and adults. It remains underused in the United States despite worldwide success, guideline support, and evidence from controlled trials.³⁷ When used as per published guidelines, oral rehydration therapy is comparable with IV therapy, but with reduced hospitalization and improved safety and expense. Small aliquots of fluid (as low as 5 mL, depending on patient size and tolerance) are administered by bottle, spoon, syringe, or nasogastric tube at regular 2- to 5-minute intervals to meet deficit and maintenance goals. After patient and family education, appropriate fluid selection is the most important factor in successful oral rehydration therapy.

Many common household fluids, including fruit juice, sport drinks, carbonated beverages, and soups, contain poorly tolerated concentrations of sugar and salt. Commercial (e.g., Rehydralyte, Pedialyte) and reconstituted liquids (oral rehydration salts or home recipe) are balanced, low-carbohydrate enteral solutions. One recipe for an oral rehydration solution containing home ingredients consists of 1 L of water, 8 teaspoons of sugar, and 1 teaspoon of salt.