Perspective

Hypovolemia is a common crisis in acute care medicine. Loss of volume is often a direct consequence of acute fluid or blood loss, but relative hypovolemia complicates many clinical conditions. Its severity ranges from mild compensated hypovolemia to shock and hypotension that place end-organ perfusion and function at risk. Fluid therapy to optimize cardiac performance and restore fluid and electrolyte balance is a cornerstone of medical support. Timely and appropriate fluid therapy maintains macrocirculatory and microcirculatory support and reduces mortality.¹ In contrast, both underresuscitation and overly aggressive fluid therapy can have an adverse impact on organ function and outcome.^2,³ Inadequate resuscitation risks leaving a patient in compensated shock. Overly aggressive fluid administration results in volume overload without improving oxygen delivery and is associated with worse clinical outcomes.⁴ In addition to sustaining circulating blood volume, intravenous (IV) fluids also correct and maintain normal acid-base and electrolyte balance. A thorough understanding of the appropriate selection, timing, and goals of fluid therapy is vital to optimize patient care.

Pathophysiology

Oxygen Delivery and Tissue Perfusion

Oxygen is delivered to cells via the circulation as a function of red blood cell mass and cardiorespiratory function. Oxygen enables continuous production of energy by cells in the form of adenosine triphosphate. Poor oxygenation compromises cell energetics and function and results in the clinical manifestations of organ dysfunction and failure.

Cardiac output is the most important determinant of oxygen delivery, and it has sufficient flexibility to compensate for reduced oxygen-carrying capacity, as well as increased metabolic demands. The physiologic response to a decrease in cardiac output is catecholamine-induced tachycardia and enhanced cardiac contractility, which attempt to maintain oxygen delivery in the face of falling stroke volume. Concomitant venoconstriction maintains intrathoracic blood volume (preload), whereas arterial vasoconstriction shunts perfusion to vital organs and maintains critical organ perfusion pressure.

Cardiac output and organ perfusion vary dramatically under changing physiologic, pathologic, and pharmacologic stimuli. Organ blood flow is directly proportional to perfusion pressure in most vascular beds. In hypovolemia, protection of arterial (organ perfusion) pressure occurs via peripheral vasoconstriction at the expense of reduced flow to noncritical circulations (e.g., hepatosplanchnic, renal, cutaneous). Consequently, arterial pressure is maintained despite hypovolemia and organ hypoperfusion.

Effective circulating volume (ECV) conceptualizes the portion of intravascular volume contributing to organ perfusion. ECV decreases with hypovolemia but does not necessarily correlate with volume status because organ perfusion is also dependent on cardiac output, vasomotor tone, and circulatory distribution. As an example, ECV may be compromised by limited cardiac output despite optimized intravascular preload status.

Volume depletion describes a state of contracted extracellular fluid with clinical implications of compromised ECV, tissue perfusion, and function. This is distinguished from dehydration, which implies an intracellular water deficit characterized by plasma hypernatremia and hyperosmolarity.

Water

Water is the most abundant constituent of the body. An adult man weighing 70 kg (154 lb) contains approximately 45 L of water, which accounts for 60% of body mass (Table 159.1). Total body water (TBW) is proportional to lean body mass and affects maintenance fluid requirements. TBW is physiologically compartmentalized into intracellular and extracellular spaces. The extracellular compartment is anatomically and conceptually divided into vascular and interstitial spaces.

Table 159.1 Size and Composition of Body Fluid Compartments*

Water freely crosses cell membranes, and osmotic forces determine the distribution of water within the body. The intracellular and extracellular fluid environments remain isosmolar but physiochemically distinct via tight regulation of dissolved solutes and proteins. Membrane-bound sodium-potassium adenosine triphosphatase pumps compartmentalize sodium and potassium to the extracellular and intracellular spaces, respectively. Active restriction of sodium to the extracellular space is the foundation of isotonic sodium-based resuscitation solutions.

Starling’s law describes the forces governing fluid flux across vascular endothelial membranes. In healthy persons, transcapillary hydrostatic force is nearly opposed by colloid oncotic pressure. Small net loss from the vascular space is ultimately returned to the systemic circulation via lymphatics. Albumin normally accounts for 80% of colloid oncotic pressure, whereas large cellular moieties such as red blood cells and platelets contribute little oncotic pressure effect. Positive hydrostatic pressure, hypoalbuminemia, and pathologic endothelial permeability are common clinical conditions that enhance extravasation of fluid from the vascular compartment. The clinical consequences include large and ongoing volume resuscitation requirements coupled with tissue (e.g., lung, gut, brain) edema, which may compromise function.

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.

Box 159.1 Anatomic Sites of Nonhemorrhagic Volume Loss

Gastrointestinal

Vomiting

Diarrhea

Drainage (ostomy, fistula, nasogastric)

Renal

Diuresis (medication, osmotic)

Salt wasting

Diabetes insipidus

Skin

Third-Space Sequestration

Intestinal obstruction

Respiratory

Respiratory distress

Insensible Loss

Fever

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.

Box 159.2 Clinical Indicators of Hypoperfusion That Warrant Consideration for a Rapid Monitored Fluid Challenge