Significant loss of intravascular volume, or hypovolemia, results in decreased transport of nutrients to the cells and impaired cellular waste removal. Profound hypovolemia can result from trauma, loss of plasma water during vomiting and diarrhea, extreme venodilation from systemic inflammation, and significant hemorrhage. Hypovolemic shock occurs when the natural neuroendocrine compensatory responses fail to restore and maintain tissue perfusion. Once 40% of the intravascular volume is lost, the neuroendocrine responses to hypovolemia become ineffective and irreversible organ failure begins.

A positive outcome during hypovolemic shock resuscitation is optimized by diligent inspection and anticipation of the disease process, aggressive fluid resuscitation and hemostasis, followed by continuous monitoring and reassessment. The goal of intravascular fluid resuscitation is to rapidly restore perfusion to chosen end-points without causing volume overload and its complications. The final outcome is dependent upon restoring cellular homeostasis.

Cellular Hemostasis

Transmembrane ion pumps regulate intracellular water maintaining cellular and organelle function integrity. Energy required to drive transmembrane ion exchange is supplied by cleavage of ATP. In contrast to 38 ATP molecules that are produced during aerobic metabolism, anaerobic metabolism produces lactate and only 2 ATP molecules per glucose molecule.

Oxygen delivery to the tissues is dependant on arterial oxygen content of blood, a functioning pump (heart) and an open conduit (vascular system). Arterial oxygen content [CaO₂=(Hb x 1.34 x SaO₂) + (PaO₂ x 0.003)] is maximized by maintaining Hg>7-10g/dL, optimizing Hg oxygen saturation (SaO₂) and dissolved oxygen (PaO₂) with supplemental oxygen administration, and reestablishing and maintaining intravascular fluid volume. Reduced delivery of oxygen and substrates to the cells can result from loss of intravascular volume (Table 1) and significant vasodilation (anesthetic agents). When oxygen delivery (DO₂) fails to keep up with oxygen consumption (VO₂), signs of shock are manifested.

Stages of Hypovolemic Shock

An acute decrease in intravascular volume causes a decrease in preload (venous return), cardiac output, and stretch in the carotid bodies and aortic arch. Baroreceptors in this location send neurological impulses to the brain stem initiating a decrease in peripheral vagal tone and an increased sympathetic stimulation. Vasoconstriction of the precapillary arteriolar sphincters, increased heart rate and increased cardiac contractility initiate a compensatory response to hypovolemia by mobilizing intravascular fluid.(Table 2) Transcapillary movement of water and activation of the renin-angiotensin-aldosterone system increase intravascular volume and venous return, which improves cardiac output and arterial flow.

If hypovolemia persists, sympathetic stimulation is amplified, clinically manifesting as significant peripheral vasoconstriction and tachycardia. Vasoactive substances produced due to local tissue hypoxia at the capillary level cause local vasodilation and increased capillary permeability resulting in maldistribution of blood flow in the hypoxic tissue beds. When chemical mediators (cytokines) produced locally in hypoxic tissues enter the systemic circulation they incite a systemic inflammatory response syndrome (SIRS). Significant vasodilation and damage at the endothelial lining resulting in increased capillary permeability further depletes intravascular volume. This multilevel response places the animal in early decompensatory (middle) stage of hypovolemic shock.(Table 2)

Prolonged and severe tissue hypoxia results in the local (intrinsic) responses overriding the sympathetic-mediated vasoconstriction, called autoregulatory escape. DO₂ is unable to meet the demands for ATP production. This manifests in circulatory collapse and insufficient arterial flow to the brain and heart. The sympathetic center in the brain mal-functions, and the heart cannot sustain either a chronotropic or inotropic response. This late decompensatory stageis the final common pathway of all forms of shock.(Table 2)

RESUSCITATION FROM HYPOVOLEMIC SHOCK

An airway is established and breathing is assessed. One hundred percent oxygen is initially delivered when assisted ventilation is required. If the animal is spontaneously breathing, oxygen is administered by nasal catheter (0.5 L/kg/minute) or flow by methods (5-15 L/minute) using a mask, hood, bag or by simply holding the oxygen delivery tubing up to the nose.

Oxygen supplementation is followed by assessment of the circulation. Control of external hemorrhage is initially accomplished by direct compression or bandaging. Vascular access is established and fluid administration initiated. Life-threatening intrathoracic or intraabdominal hemorrhage may require emergency surgical intervention for hemostasis.

Vascular access is obtained by rapid catheterization of peripheral veins. If the animal is in the decompensatory stage of hypovolemic shock, and weighs over 25kg, multiple venous catheters with the largest bore, shortest length tube are placed. Intraosseous catheter placement in the proximal femur, humerus, cranial tibia or wing of the ilium may be faster and easier to place in young and small animals.

Placing the fluid bag under pressure permits rapid volume infusion and using Y-set infusion adapters allows infusion of multiple types of fluids into a single catheter. Fluid selection is based on the clinical stage of hypovolemic shock, and underlying diseases.

Fluid selection is further described in Table 3.The goal of intravascular fluid resuscitation is to rapidly restore perfusion to chosen end-points (Table 2) without causing volume overload and its complications (pulmonary, peripheral and brain edema). Buffered isotonic crystalloid solutions, such as lactated Ringer's solution, Normosol-R®, and Plasmalyte 7.4®, provide a more normal pH level, and may more rapidly and efficiently restore normal pH for this purpose, however perfusion end-points may be more difficult to reach without the complications of edema when treating decompensatory shock states.

Crystalloid volume and rate of administration depends on a number of factors that can determine the ability of the interstitial space to handle the increased fluid load.(Table 3) When large quantities of isotonic crystalloids are rapidly administered intravenously, there is an immediate increase in hydrostatic pressure, a decrease in colloid osmotic pressure (COP) and extravasation of large fluid quantities into the interstitial spaces. Extreme care must be given when correcting perfusion deficits with crystalloids alone in animals with pathology of the heart and brain, if there is significant impairment of renal function, increased vascular permeability, or if significant hemorrhage is occurring.

Hypertonic saline provides an additional osmotic attraction for water to flow from the interstitium into the vessel during resuscitation of catastrophic hypovolemic shock. Using hypertonic saline with a synthetic colloid may augment intravascular retention of volume.

By administering colloids in conjunction with crystalloids during fluid resuscitation, less total fluid volume is required, there is less tendency toward fluid overload, and resuscitation times are shorter. Plasma COP can be maintained near normal with synthetic colloids, favoring intravascular fluid retention.

When the animal requires red blood cells, clotting factors, antithrombin III or albumin, blood products are necessary. Dogs and cats receiving whole blood or a combination of packed red blood cell-colloid transfusion should be blood typed and cross-matched, time permitting. If time is a limiting factor, a universal donor (DEA 1.1 negative) should be chosen for the canine patient. Blood typing or cross matching is always recommended for the cat, but may not be feasible in the catastrophic cases.

Hemoglobin-based oxygen-carrying solutions (e.g., Oxyglobin®) contain hemoglobin that binds with pulmonary oxygen and transport it to the tissues where it is off loaded to the cells. Because of its molecular size, it is smaller than a red blood cell and able to pass through the microcirculation more readily. This may make it the ideal fluid to administer during situations of severe anemia, and/or hypovolemia caused by acute hemorrhage or maldistribution of blood flow. In addition to carrying oxygen into smaller spaces, there also may be a vasoconstricting effect that can reduce the volume required for resuscitation.

Dextrans, and hydroxyethyl starches (HES) are synthetic colloids able to attract and retain water in the intravascular space. Larger molecular weight colloids (i.e., hydroxyethyl starches and dextran 70) will retain water longer, maintaining colloid properties as they are broken down into smaller particles prior to elimination. This characteristic is advantageous when sustained volume support is required during increased capillary permeability, and when there is less tolerance of rapid intravascular volume increases (e.g., during brain and pulmonary injury, cardiac insufficiency, or in hypovolemic cats).

Hypothermia, especially in the cat, can significantly limit the cardiovascular response to fluid resuscitation. Wrapping the hypothermic animal in a blanket or plastic wrap will restrict continued loss of body heat by convective currents. Initial administration of warmed fluids (at room or normal body temperature) using a 5 ml/kg hetastarch bolus concurrently with 10-15 ml/kg warm isotonic crystalloid fluid bolus. Active external warming should occur once fluid resuscitation has been initiated. The arterial blood pressure and rectal temperature are frequently reassessed. If a hypothermic cat becomes normothermic, but the systolic blood pressure remains below 70 mmHg, cardiac function should be assessed. Small volume resuscitation efforts are continued up to a total of 40ml/kg colloid administration if no heart disease is present. If fluid resuscitation has not reestablished the arterial blood pressure >70 mmHg, or should a hypothermic cat (rectal temperature < 98 degrees F) not respond to aggressive warming efforts (generally within 1 hour), vasopressors, such as dopamine, should be considered (see below) until body temperature has been normalized.

Analgesics

Pain will exacerbate the sympathetic response occurring during hypovolemic shock, causing a tachycardia or hypertension. Other than being a humane treatment, low dose narcotics combined with low dose anxiolytics can remove additional catecholamine reaction caused by pain, providing a more accurate assessment of the baroreceptor response to hypovolemia and resuscitation. Intravenous, reversible agents such as butorphanol or fentanyl and benzodiazepines have limited adverse cardiovascular effects in the painful, hypovolemic animal. Their actions are also easily reversed with intravenous antidotes. Administering local analgesia with lidocaine or bupivacaine, or administering epidural analgesia will limit the systemic response to intravenously administered analgesics.

Vasopressors

If fluid administration alone is unsuccessful at restoring perfusion end-points during decompensatory shock, underlying causes of nonresponsive shock must be investigated and treated.(Table 4) Echocardiographic evaluation of cardiac contractility is ideal for making the decision to use positive inotropes versus vasomotor drugs.

Positive inotropic drugs such as dobutamine (dogs: 5-10mcg/kg/min; cats: 1.5-5 mcg/kg/min), dopamine (3-5 mcg/kg/min), and epinephrine (0.005-1 mcg/kg/min) increase stroke volume and cardiac output. Epinephrine will increase myocardial oxygen demand more than delivery predisposing the myocardium to arrhythmias and producing a lactic acidosis. Vasopressors such as increased dose dopamine (5-15 mcg/kg/min), phenylephrine (1-3 mcg/kg/min), norepinephrine (1-10 mcg/kg/min), and epinephrine (1-2 mcg/kg/min) may be used in catastrophic stages of hypovolemic shock.

When circulatory drugs are required to maintain cardiac output and blood pressure prognosis decreases significantly.

Glucocorticosteroids

At this time insufficient clinical evidence in companion animals exists to support the administration of high dose glucocorticosteroids in hypovolemic shock. Animals with an absolute deficiency in cortisol may benefit from physiologic doses 0.3 mg/kg every 8 hours of methylprednisone during resuscitation and recovery (e.g., hypoadrenocorticism or nonresponsive hyperdynamic septic shock).

Table 1. Causes of acute intravascular volume loss

Table 2. Clinical parameters and resuscitation endpoints monitored during resuscitation from shock

Table 3. Fluid types and doses

IV: Intravenous; IO: Intraosseous; EP: endpoint parameter; HES: hydroxyethylstarch; DEX: dextran-70; CRI Constant rate infusion; HTS: hypertonic saline; PT: prothrombin time; PTT: activated partial thromboplastin time; *up to 20ml/kg; **if EP not reached, look for causes of nonresponsive shock

Table 4. Causes of nonresponsive shock

 Inadequate intravascular volume

 Ongoing fluid losses (blood or plasma)

 Severe pain

 Cardiac arrhythmias

 Cardiac tamponade

 Myocardial depression or failure

 Electrolyte imbalances

 Acidemia/alkalemia

 Hypoglycemia

 Neurological failure

 Organ ischemia

 Hypoxemia

 Inadequate oxygen carrying ability

 Inadequate colloid osmotic pressure

 Excessive peripheral vasoconstriction

 Excessive peripheral vasodilation

 Decreased venous return