During times of increasing blood volume such as in heart failure, a compensatory renal response is:

Physiologic Response to Hypovolemia

Acute blood loss or severe hypovolemia related to dehydration decreases venous return.163 This can be seen with acute blood loss (usually greater than 20% of blood volume), severe burns, or prolonged vomiting or diarrhea that depletes body fluids. As a result, cardiac output falls and clinical manifestations of shock ensue. Several compensatory mechanisms are initiated by acute hypovolemia (Box 1.1). The dominant compensatory mechanism in shock is a reduction in carotid sinus baroreceptor inhibition of sympathetic outflow to the cardiovascular system. This increased sympathetic outflow results in several effects: (1) arteriolar vasoconstriction, which greatly increases peripheral vascular resistance; (2) constriction of venous capacitance vessels, which increases venous return to the heart; and (3) an increase in the heart rate and force of contraction, helping maintain cardiac output despite significant loss of volume.160

The value of sympathetic reflex compensation is illustrated by the fact that 30% to 40% of blood volume can be lost before death occurs. When sympathetic reflexes are absent, a loss of only 15% to 20% of blood volume may cause death.160 Increased sympathetic nerve activity results in the commonly recognized physical signs of shock, including pallor, cool clammy skin, rapid heart rate, muscle weakness, and venous constriction. An inadequate immediate compensatory response will result in dizziness, altered mental status, or loss of consciousness.164 The central nervous system response to ischemia further stimulates the sympathetic nervous system after arterial pressure falls below 50 mm Hg.160 Subsequent compensatory mechanisms that work to restore blood volume to a normal level include the release of angiotensin and antidiuretic hormone (vasopressin). This causes arteriolar vasoconstriction, conservation of salt and water by the kidneys, and a shift in fluid from the interstitium to the intravascular space.164

Several investigators have examined the changes in blood pressure and pulse that occur in supine patients with blood loss.158,159,161,165 Collectively, these studies have shown variable individual hemodynamic responses to acute blood loss of up to 1 L. The frequent inability to detect significant loss of volume with supine vital signs, and the observation that syncope frequently develops in patients with acute volume loss on rising, led to the investigation of the use of orthostatic vital signs to detect occult hypovolemia.

I Introduction

The term hypovolemia refers collectively to two distinct disorders: (1) volume depletion, which describes the loss of sodium from the extracellular space (i.e., intravascular and interstitial fluid) that occurs during gastrointestinal hemorrhage, vomiting, diarrhea, and diuresis; and (2) dehydration, which refers to the loss of intracellular water (and total body water) that ultimately causes cellular desiccation and elevates the plasma sodium concentration and osmolality.1 Chapter 17 discusses the accuracy of abnormal vital signs in patients with volume depletion; this chapter discusses assorted additional findings.

Hyponatremia With Extracellular Fluid Volume Depletion

Patients with hyponatremia who have ECF volume depletion have sustained a deficit in total body Na+ that exceeds the deficit in TBW. The decrease in ECF volume is manifested by physical findings such as flat neck veins, decreased skin turgor, dry mucous membranes, orthostatic hypotension, and tachycardia. If sufficiently severe, volume depletion is a potent stimulus to AVP secretion. When the osmoreceptors and volume receptors receive opposing stimuli, the former remains active but the set point of the system is lowered (seeFig. 15.7). Thus, in the presence of hypovolemia, AVP is secreted and water is retained, despite hypoosmolality. Whereas the hyponatremia in this setting clearly involves a depletion of body solutes, the concomitant AVP-mediated retention of water is critical to the pathologic process producing hyponatremia.

As depicted in the flow chart inFig. 15.17, measurement of the urine [Na+] concentration is helpful in assessing whether the fluid losses are renal or extrarenal in origin. A urine [Na+] of less than 30 mEq/L reflects a normal renal response to volume depletion and indicates an extrarenal source of fluid loss. This is usually seen in patients with gastrointestinal disease with vomiting or diarrhea. Other causes include loss of fluid into a third space, such as the abdominal cavity in pancreatitis or the bowel lumen with ileus. Burns and muscle trauma can also be associated with large fluid and electrolyte losses. Because many of these pathologic states are associated with increased thirst, an increase in orally ingested or parenterally infused free water can lead to hyponatremia.

Hypovolemic hyponatremia in patients whose urine [Na+] is higher than 30 mEq/L indicates the kidney as the source of the fluid losses. Diuretic-induced hyponatremia, a commonly observed clinical entity, accounts for a significant proportion of symptomatic hyponatremia in hospitalized patients. It occurs almost exclusively with thiazide rather than loop diuretics. This is most likely because, whereas both classes of diuretics can impair urine diluting ability, loop diuretics also impair the generation of the medullary interstitial concentrating gradient, thus limiting the maximal urinary concentration that can be achieved. The hyponatremia is usually evident within 14 days in most patients, but occasionally can occur as late as 2 years after the initiation of therapy.298 Underweight women appear to be particularly prone to this complication, and advanced age has been found to be a risk factor in some, but not all, studies.298–300 A careful study of diluting ability in older adults has revealed that thiazide diuretics exaggerate the already slower recovery from hyponatremia induced by water ingestion in this population.301

Diuretics can cause hyponatremia by several mechanisms: (1) volume depletion, which results in impaired water excretion by enhanced AVP release and decreased tubular fluid delivery to the diluting segment; (2) a direct effect on the diluting function of the thick ascending limb or distal convoluted tubule; and (3) K+ depletion that frequently accompanies diuretic use, which contributes to the loss of total body exchangeable solute (Na+ + K+).302 The concomitant administration of potassium-sparing diuretics does not prevent the development of hyponatremia. Although the diagnosis of diuretic-induced hyponatremia is frequently obvious, surreptitious diuretic abuse should always be considered in patients in whom other electrolyte abnormalities and high urinary Cl− excretion suggest this possibility. Recent genetic and phenotyping studies have suggested that an inherited defect in PGE2 uptake in the collecting duct may confer an increased risk of thiazide-induced hyponatremia, which raises the possibility that patients at risk of this adverse effect of thiazides may be able to be identified before exposure to the drug.303,304

II. THE FINDINGS AND THEIR PATHOGENESIS

Many of the traditional signs of hypovolemia—dry mucous membranes, sunken eyes, shriveled skin and tongue, confusion—originate in classic descriptions of cholera as findings of patients near vascular collapse.2 Presumably, cellular dehydration, interstitial space dehydration, and poor perfusion contribute to these signs; however, studies of their pathogenesis are unavailable.

Poor skin turgor refers to the slow return of skin to its normal position after being pinched between the examiner's thumb and forefinger.3,4 The protein elastin is responsible for the recoil of skin, and in vitro experiments show that its recoil time increases 40-fold after loss of as little as 3.4% of its wet weight.3 Elastin also deteriorates with age, however, suggesting that poor skin turgor may be a less specific finding of hypovolemia in elderly patients.

Severe Hypovolemia

Hypovolemia leads to a decrease in LV end-diastolic area (EDA) and end-systolic area (ESA), but at baseline there is wide variability in the normal ranges.105 For practical purposes, qualitative assessment of chamber size provides the most useful information if monitored serially in the operating room or in the setting of significant hypovolemia, where EDA will be markedly reduced. It is important to distinguish hypovolemia from distributive shock, where ESA is also decreased but the EDA area will be normal.106 End-systolic cavity obliteration (sometimes described as “kissing walls”) is frequently associated with decreased EDA and hypovolemia, but may also occur in high inotropic or vasodilatory states.105

As previously described, IVC diameter and cIVC can be used to estimate the RAP in spontaneously breathing individuals.77 Central venous pressure, however, is a poor predictor of fluid responsiveness.107 Whether cIVC predicts fluid responsiveness during spontaneous ventilation is an area of active debate,108–111 and has been examined in several studies.112–117 In many instances, spontaneously breathing patients with cIVC of more than 40% to 50% will respond to fluid administration,112,115,117 but this is not found consistently,113,114 and does not necessarily identify nonresponders.112,115 We would encourage the reader to read the primary literature to gain a more in-depth understanding of the topic prior to attempting to use cIVC in the assessment of hypovolemia.

Predictors of fluid responsiveness applicable in patients who undergo passive mechanical ventilation, typically in the setting of critical illness, are covered in theCritical Care section of the chapter.

Hypovolemia

Hypovolemia is common in surgical, trauma, and critically ill patients. Hypovolemia is defined as a depletion of the effective circulating blood volume. It is due to losses either from the body or into body cavities – so-called ‘absolute hypovolemia’ – or to sequestration of fluid within the body as a result of generalized diffuse capillary leak, so-called ‘relative hypovolemia’ (Table 59.1). Large fluid deficits become obvious in systemic inflammatory states (e.g. sepsis syndrome), characterized by panendothelial injury and increased capillary permeability with loss of proteins and fluids from the intravascular to the ISF. Therefore, the effective circulating volume is low with an expanded ECF volume in many conditions, such as sepsis or sepsis syndrome, liver disease, and anaphylaxis. Absolute or relative hypovolemia can be accentuated during anesthesia because sympathetic reflexes are blunted. Anesthetic drugs themselves, including volatile and intravenous agents, may contribute to relative hypovolemia by causing further vasodilatation. Spinal and epidural anesthesia produces relative hypovolemia by blocking efferent sympathetic vasomotor signals resulting in venous pooling.

During hypovolemia the body tries to perfuse the vital organs, including the heart and the brain, by sustained vasoconstriction at the expense of other organs such as the gut, liver, and kidneys. In severe protracted hypovolemia systemic perfusion and the function of the microcirculation are impaired. This then triggers a vicious cycle of progressive tissue damage that may finally lead to the development of multiple organ failure. The primary objective of fluid therapy is to restore and maintain adequate intravascular blood volume in order to restore oxygen delivery, organ perfusion, and microcirculatory flow, and to avoid the activation of a complex series of damaging mediators.

Hypovolemia

Hypovolemia is an uncommon primary cause of neonatal shock, especially during the first postnatal days. In preterm newborns, there is no evidence that hypotensive babies as a group are hypovolemic.125 However, the recent finding of improved hemodynamics following delayed compared with immediate cord clamping in preterm infants suggests a possible role for hypovolemia in the development of cardiovascular compromise during postnatal transition.126,127

Hypovolemia causes low cardiac output and hypotension by decreasing the preload. Hypovolemia can result from loss of circulating blood volume after hemorrhage (absolute hypovolemia) or from inappropriate increases in the capacitance of the blood vessels as in vasodilatory shock (relative hypovolemia). In addition, the positive intrathoracic pressure associated with positive pressure mechanical ventilation reduces venous return and hence preload and cardiac output in ventilated preterm and term neonates.128

Absolute hypovolemia in the neonate can be caused by intrapartum fetal blood loss resulting from a hemorrhage from the fetal side of the placenta, from acute fetal-maternal hemorrhage, or from acute fetal-placental hemorrhage. The latter may occur in neonates with breech presentation or a tight nuchal cord, in whom the umbilical cord comes under significant pressure.129 Postnatal hemorrhage may occur from any site and is frequently associated with endothelial damage and disseminated intravascular coagulation induced by perinatal infections or asphyxia. Acute abdominal surgical problems and conditions associated with increased capillary leak with loss of fluid into the interstitium can also lead to significant decreases in the circulating blood volume.

CVOs in the Regulation of Salt Appetite

Hypovolemia also activates salt appetite (to restore lost solute), albeit on a slower time scale than thirst. ANG and aldosterone play roles in inducing salt appetite during hypovolemia, perhaps acting synergistically. The possible mechanism of the synergism is quite elegant: aldosterone may act via a nuclear receptor to increase expression of the AT1 subtype of receptor protein in the SFO, leading to a potentiated response of SFO neurons to ANG and thus increased salt appetite. Available data also suggest an inhibitory role of AP in salt appetite because AP lesions enhance NaCl solution intake.

Hypovolemia.

Hypovolemia is common following lung transplantation due to relative fluid restriction, blood loss, interstitial (third-space) losses, and the effects of epidural analgesia. Occasionally, large fluid losses can occur into the pleural spaces and not be revealed in the chest drains or on the chest radiograph. TEE examination or chest ultrasound should be performed if intrathoracic fluid accumulation is suspected. Patients who are critically unwell with severe reperfusion injury can develop marked third-space losses and whole-body edema. Hypovolemia dramatically exacerbates hypotension caused by other conditions (e.g., raised intrathoracic pressure).

Hypovolemia

Hypovolemia may be absolute (loss of intravascular volume), relative (increased venous capacitance), or combined such as is often seen in septic shock. Hypovolemia results in cardiovascular compromise primarily by the decrease in cardiac output (systemic blood flow) caused by the decrease in preload. In addition, if blood loss is the primary cause of hypovolemia, the associated decrease in oxygen carrying capacity contributes to the development of the circulatory compromise. Hypovolemia is probably overdiagnosed in neonatology, because it is a relatively uncommon primary cause of circulatory compromise, especially during the first postnatal day. In the preterm newborn there is no evidence that hypotensive neonates as a group are hypovolemic (Barr et al, 1977; Wright and Goodhall, 1994). However, when hypovolemia occurs, it can be difficult to detect clinically.

Absolute hypovolemia in the newborn can be due to several conditions. Intrapartum fetal blood loss is usually caused by an open bleed from the fetal side of the placenta, and therefore it is likely to be detected. More difficult to diagnose is the closed bleeding of an acute fetomaternal hemorrhage or an acute fetoplacental hemorrhage. The latter can occur during delivery where the umbilical cord comes under some pressure (breech presentation or nuchal cord). Because the umbilical vein is occluded before the artery, blood continues to be pumped into the placenta, and if the cord is clamped early, this blood remains trapped in the placenta. This probably happens to some degree in all babies with tight nuchal cords who, as a group, have lower hemoglobin levels (Shepherd et al, 1985). However, in some neonates, a tight nuchal cord may also cause severe circulatory compromise (Vanhaesebrouck et al, 1987). Postnatal hemorrhage may occur from any site and is frequently associated with perinatal infections or severe asphyxia-induced endothelial damage and the ensuing disseminated intravascular coagulation. Finally, acute abdominal surgical problems and conditions associated with the nonspecific inflammatory response syndrome and subsequent increased capillary leak with loss of fluid into the interstitium can lead to significant decreases in the circulating blood volume. Iatrogenic causes of absolute hypovolemia include inadequate fluid replacement in conditions of increased insensible losses in the very preterm neonate and gastroschisis before closure of the defect, or the inappropriate use of diuretics.

Relative hypovolemia, that is, a decrease in the effective circulating blood volume, may occur in pathologic conditions leading to vasodilation such as in conditions associated with the nonspecific inflammatory response syndrome (sepsis, necrotizing enterocolitis [NEC], asphyxia, major surgical procedures, use of extracorporeal membrane oxygenation [ECMO]). In addition, the use of afterload-reducing agents (e.g., milrinone, PGE2) may cause significant vasodilation (especially venodilation), thereby decreasing the effective circulating blood volume.

Finally, absolute and relative hypovolemia most frequently occurs in conditions associated with the nonspecific inflammatory response syndrome such as sepsis, asphyxia, and major surgical procedures.