Resuscitative Fluid Therapy for Circulatory Shock

Deborah Silverstein, DVM, Diplomate ACVECC

Resuscitative fluid therapy commonly refers to the treatment of circulatory shock and utilizes intravenous fluids to help restore circulating blood volume.^1,2 

Shock is best defined as inadequate cellular energy production.³ When oxygen delivery (DO₂) to the tissues is insufficient relative to tissue oxygen consumption (VO₂), an energy deficit occurs. The Figure illustrates contributors to DO₂ and portrays how inadequacy of any of these factors can lead to shock.

Classifying Shock

In 1972, Hinshaw and Cox proposed a classification scheme for shock.⁴ The main categories were:

• Hypovolemic: Inadequate circulating volume (eg, hemorrhage)
• Obstructive: Extracardiac obstruction of blood flow (eg, cardiac tamponade)
• Distributive: Maldistribution of blood flow and volume (eg, sepsis)
• Cardiogenic: Primary cardiac pump failure.

Newer shock classifications have been proposed but all of these can be included in 1 or more of the previous 4 categories and have yet to be universally accepted:

• Metabolic (eg, hypoglycemia, mitochondrial dysfunction)
• Endocrine (eg, hypoadrenocorticism, hypothyroidism, hyperthyroidism)
• Hypoxemic (eg, severe anemia)
• Neurogenic (eg, spinal cord transection)
• Anaphylactic.

Consequences of Shock

Rapid progression of shock can be lethal due to major organ failure (eg, heart, brain). A more insidious progression causes cellular membrane dysregulation, which leads to:

• Exposure of subendothelial collagen
• Activation of platelets, clotting cascade, fibrinolytic, and kinin systems
• Bacterial translocation from the intestinal tract.

Subsequently, systemic inflammatory response, sepsis, and multiple organ dysfunctions often result. Despite adequate shock reversal, they may persist and can result in death.

Fluid Therapy Indications

To optimize the chance of a successful outcome, rapid, aggressive therapy and appropriate monitoring is warranted as soon as a state of shock is identified. While contraindicated for treatment of cardiogenic shock, intravenous fluid therapy is the cornerstone of treatment for hypovolemic and distributive shock.

Depending on the location of the obstruction, responsiveness to fluid therapy varies with obstructive forms of shock. Resuscitative fluid therapy can be attempted, but treatment of the underlying disorder is ultimately essential (ie, pericardiocentesis for pericardial effusion causing tamponade).

Types of Fluid Therapy

The arsenal of fluid types available for the treatment of shock comprises:

• Isotonic and hypertonic crystalloids
• Synthetic colloids
• Hemoglobin-based oxygen-carrying solutions
• Blood products.

The patient’s clinical condition and type of shock dictates which fluid type to employ and is further discussed in the following sections.

Crystalloid Fluids

Description

Crystalloid fluids primarily consist of water combined with sodium, chloride, and/or glucose. Depending on the type of fluid, it may also contain other electrolytes, such as potassium and calcium, and buffers, such as lactate, acetate, and gluconate.

Based on the tonicity (effective osmolality) when compared to the extracellular fluid compartment, crystalloids are further subdivided into:

• Isotonic
• Hypotonic
• Hypertonic

Isotonic Crystalloids

Isotonic crystalloids contain simple electrolytes (sodium and chloride) in proportions similar to that of plasma. Hence, they are also called replacement fluids. Examples include:

• 0.9% sodium chloride
• Lactated Ringer’s solution; contains potassium, calcium, and lactate as buffers
• Normosol-R (hospira.com) and Plasma-Lyte-A (baxter.com); both contain potassium, magnesium, acetate, and gluconate as buffers.

Indications
Isotonic crystalloids are the least expensive resuscitative fluids and are commonly used as the initial resuscitative fluid for the treatment of patients in fluid-responsive shock.

Dosing
The empirical shock dosage is the equivalent of the patient’s blood volume: 90 mL/kg in the dog and 50 mL/kg in the cat.⁵ A common dosing approach consists of administering -+ to 1/3 of the shock dose; then reassessing the patient’s cardiovascular parameters prior to further administration.

Considerations & Precautions
These fluids rapidly redistribute into the extracellular compartment following administration and approximately 25% of the delivered volume remains in the vascular space 30 minutes postinfusion.6 While this is beneficial in dehydrated patients, overzealous use should be avoided to prevent volume overload and interstitial, pulmonary, or cerebral edema.

Furthermore, large volumes of isotonic crystalloids cause hemodilution of blood constituents and may lead to cardiac and pulmonary complications, gastrointestinal dysmotility, coagulation disturbances, and immunological and inflammatory mediator dysfunction.⁷

Hypotonic Crystalloids

Because rapid intravasacular infusion of hypotonic fluids does not lead to a sustained intravascular volume increase but does lead to potentially dangerous changes in cellular osmolality, they are contraindicated as resuscitative fluids.

Hypertonic Crystalloids

Hypertonic saline is a sodium chloride solution with an osmolality greater than the patient’s plasma osmolality. The usual concentration used for fluid resuscitation is approximately 7.5%, which has an osmolality of 2400 mOsm/L.
After rapid infusion, an osmotic gradient is created that draws water from the intracellular and interstitial space into the intravascular space. Therefore, the vascular volume expansion is greater than the infused volume (approximately 3 times greater).^8,9

Indications
Hypertonic saline presents a good option for patients with traumatic brain injury or when rapid intravascular volume expansion is required. Additional benefits include increased cardiac contractility, mild peripheral arteriolar vasodilation and immunomodulatory effects.

Its use, however, is contraindicated in patients that are dehydrated, hyperosmolar, or hypokalemic and it is controversial in patients that have uncontrolled hemorrhage (eg, intracranial or intra-abdominal).¹⁰

Dosing
The usual shock dosage of hypertonic saline is 4 to 7 mL/kg in dogs and 3 to 4 mL/kg in cats, administered over approximately 10 minutes. Infusion rates greater than 1 mL/kg/min may cause a vagally mediated bradycardia, vasodilation, and bronchoconstriction.

To prolong the intravascular volume expansion effect, a hypertonic saline/synthetic colloid mixture can be administered:

• 1:2.5 ratio of 23.4% sodium chloride:hetastarch = approximately 7.5% saline mixture (44 mL of 23.4% sodium chloride in 106 mL hydroxyethyl starch)
• It should be administered in small volumes (up to 5 mL/kg) over 5 to 10 minutes.

Considerations & Precautions
As with isotonic crystalloid solutions, the infused sodium chloride solution will ultimately equilibrate between the intravascular and interstitial space. In addition, the transient hyperosmolality will cause an osmotic diuresis.

The volume expanding effect lasts approximately 30 minutes8 and subsequent isotonic crystalloid infusion is required (see Dosing). As discussed above, concurrent colloid administration prolongs the volume effect and may be beneficial.

Synthetic Colloids

Description

Synthetic colloids are large molecules (molecular weight > 20 kilodaltons [kDa]) that do not readily escape across the capillary membrane if normal permeability is present. Synthetic colloids are suspended in isotonic crystalloid-base solutions. When infused IV, the macromolecules increase the oncotic pressure, resulting in fluid movement from the extravascular into the intravascular space.

Commercialized synthetic colloids include:

• Glucose polymers (dextran)
• Gelatins
• Hemoglobin-based oxygen carriers (HBOC)
• Hydroxyethyl starches.

Glucose Polymers & Gelatins

Historically, the most commonly used and studied glucose polymer was Dextran 70; however, it is no longer commercially available. Gelatin solutions, a chemical modification of bovine collagen, have limited use due to their short duration of action and numerous side effects.

Hemoglobin-Based Oxygen Carriers

Indications
HBOC solutions may be beneficial in animals with severe anemia because they increase oxygen delivery to the tissues. HBOC may also increase perfusion of capillary beds with microvascular thrombosis due to the small size of free hemoglobin.

Considerations & Precautions
Despite the aforementioned potential benefits of HBOC and its long shelf life, it is not widely used due to inconsistent supply, undesirable side effects, and lack of clear benefit over natural blood products.

Hydroxyethyl Starches

Hydroxyethyl starches are composed of amylopectin polymers with specific chemical modifications that dictate their pharmacokinetics and elimination.

Commercially available hydroxyethyl starch products differ by their concentration, average molecular weight, and degree of substitution (see The Finer Features of Hydroxyethyl Starches) and include:

• Hetastarch
• Pentastarch
• Tetrastarch.

Indications
Although the use of hydroxyethyl starches alone have no proven benefit over the use of crystalloid solutions alone for the treatment of fluid responsive shock, they remain a good adjunct treatment, especially in patients with low colloid osmotic pressure or increased vascular permeability.

Dosing
The recommended shock dose of hetastarch is up to 20 mL/kg in dogs and up to 10 mL/kg in cats. A common practice consists of administering increments of -+ to -+ of the total shock dose, followed by reassessment of cardiovascular parameters.

Considerations & Precautions

Use of hydroxyethyl starches may lead to:

• Fluid overload and hemodilution (associated with large infused volumes)
• Coagulation abnormalities due to decreased coagulation factors VIII and von Willebrand, thrombocytopathia, and increased fibrin clot fragility.¹²

Although not contraindicated in patients with coagulopathies, caution should be exercised. Renal impairment and allergic reactions have been reported in people, but not small animals.^13,14,15

Blood Products

Fresh whole blood contains all the elements of blood:

• Red blood cells
• Coagulation factors
• White blood cells
• Immunoglobulins
• Platelets
• Albumin.

The separation of red blood cells and plasma provides various blood component products that allows for longer preservation of the units and more specific therapy. The product type should be tailored to the patient’s needs.

Packed Red Blood Cells

Indications
Packed red blood cell transfusion is indicated in patients with acute anemia (hematocrit < 25%) and persistent clinical cardiovascular instability.¹⁶

Dosing
Packed red blood cells can be administered at a dose of 10 to 15 mL/kg to raise the hematocrit by 10%.

Fresh Frozen Plasma

Indications
Fresh frozen plasma is indicated to replenish coagulation factors in patients with prolonged coagulation times. However, despite being a source of albumin, its colloidal effect is limited due to its relatively low concentration compared to synthetic colloids.

Dosing
Fresh frozen plasma can be administered at a dose of 10 to 15 mL/kg.

Fresh Whole Blood

Indications
Fresh whole blood provides the benefits of both previously mentioned products (packed red blood cells and fresh frozen plasma) but is also a source of platelets, which is beneficial in patients with:

• Severe thrombocytopenia or thrombocytopathia-induced bleeding
• Massive blood loss
• Severely thrombocytopenic patient in need of surgery.

Dosing
Fresh whole blood is administered at a dose of 20 to 25 mL/kg. Ideally, blood-typing and cross-matching are performed before any blood product transfusion.
In addition, when time allows, any blood product should be infused over 1 to 4 hours to allow for adverse reaction monitoring. However, faster administration may be warranted in patients with severe ongoing hemorrhage until hemostasis can be achieved.

Considerations & Precautions
Potential adverse events associated with transfusion therapy include:

• Acute or delayed immunologic reactions
• Electrolyte imbalances (ie, hypocalcemia, hypomagnesemia, hyperkalemia)
• Transmission of infectious agents.

Another major disadvantage of blood products is their associated cost and limited availability as compared to other types of resuscitative fluids.

Overview of Therapy

An Overview of Resuscitative Fluid Therapy table is available below.

DO₂ = oxygen delivery;
HBOC = hemoglobin-based oxygen carriers;
kDa = kilodalton; VO₂ = oxygen consumption

References

1. Parkins WN, Perlmutt JH, Vars HM. Evaluation of crystalloidal solutions in hemorrhaged dogs. Amer J Physiol 1952; 170:351.
2. Fogelman MJ, Wilson BJ. A different concept of volume replacement in traumatic hypovolemia observations on injured man and animal. Amer J Surg 1960; 99(5):694-701.
3. Chaudry IH. Cellular mechanisms in shock and ischemia and their correction. Amer J Physiol 1983; 245(2):R117-R134.
4. Hinshaw LB, Cox BG (eds). The 50 Fundamental Mechanisms of Shock. New York City: Plenum Press, 1972, p 13.
5. Day TK, Bateman S. Shock syndromes. In DiBartola SP (ed): Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice, 3rd ed. St. Louis: Elsevier, 2006, pp 540-564.
6. Griffel MI, Kaufman BS. Pharmacology of colloids and crystalloids. Crit Care Clin 1992; 8(2):235-253.
7. Cotton BA, Guy JS, Morris JA Jr, Abumrad NN. The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies. Shock 2006; 26(2):115-121.
8. Silverstein DC, Aldrich J, Haskins S, et al. Assessment of changes in blood volume in response to resuscitative fluid administration in dogs. J Vet Emerg Crit Care 2005; 15(3):185-192.
9. Kramer GC. Hypertonic resuscitation: Physiologic mechanisms and recommendations for trauma care. Trauma 2003; 54(5):S89-S99.
10. Krausz MM. Controversies in shock research: Hypertonic resuscitation—pros and cons. Shock 1995; 3(1):69-72.
11. Smith GJ, Kramer GC, Perron PR, et al. A comparison of several hypertonic solutions for resuscitation of bled sheep. J Surg Re 1985; 39:517-528.
12. Chan DL. Colloids: Current recommendations. Vet Clin North Am Small Anim Pract 2008; 38(3):587-593.
13. Niemi TT, Miyashita R, Yamakage M. Colloid solutions: A clinical update. J Anes 2010; 24(6):913-925.
14. Grundmann U, Heinzmann A, Schwering L, et al. Diagnostic approach identifying hydroxyethyl starch (HES) triggering a severe anaphylactic reaction during anesthesia in a 15-year-old boy. Klinische Padiatrie 2010; 222(7):469-470.
15. Ring J, Messmer K. Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet 1977; 1(8009):466-469.
16. De Laforcade AM, Silverstein DC. Shock. In Silverstein DC, Hopper K (eds): Small Animal Critical Care Medicine, 1st ed. St. Louis: Elsevier, 2009, pp 41-45.

Deborah Silverstein, DVM, Diplomate ACVECC, is an assistant professor of critical care in the Department of Clinical Studies at the University of Pennsylvania School of Veterinary Medicine. Her primary areas of interest include shock fluid therapy, pathogenesis of sepsis and septic shock, and microcirculatory alterations in critically ill animals. Dr. Silverstein received her DVM from University of Georgia and completed a residency in small animal emergency and critical care at University of California-Davis and an internship in small animal medicine and surgery at University of Georgia.

Alexandre Proulx, DVM, is a third-year resident in emergency and critical care at the University of Pennsylvania School of Veterinary Medicine. His interests include acid-base disturbances and extracorporeal life support. Dr. Proulx received his DVM from University of Montreal and completed a rotating small animal internship at University of Pennsylvania’s Matthew J. Ryan Veterinary Hospital.