Practical tips for fluid and colloid therapy (Proceedings)

April 1, 2010

Lauren A. Trepanier, DVM, PhD, DACVIM, DACVCP

Article

Hypovolemia vs. dehydration

A. Hypovolemia = decrease in effective circulating vascular volume

B. Dehydration = loss of total body water

Factors that affect the distribution of administered fluids

A. Sodium content of fluids

1. Fluids with a sodium content approximately equal to that of normal plasma (or about 145 meq/L) will equilibrate between plasma and extracellular tissues

2. Fluids with a sodium content much lower than plasma (e.g. 5% dextrose) will tend to "dilute" plasma sodium

a) This leads to water either entering cells or being eliminated as excess water in the urine

b) The end result is that very little of sodium-free fluid remains in the vascular space to expand blood volume

3. Fluids with a sodium content higher than normal plasma (e.g. hypertonic saline) will tend to draw water out of cells and into the vascular and extracellular spaces

a) This is beneficial for immediate treatment of a patient with a sudden drop in blood pressure

b) This is undesirable in a dehydrated patient (one who has lost total body water)

B. Colloidal content of fluids

1. Colloids, or large molecules that remain in the vascular space and "hold on" to plasma water, may take the form of proteins (especially albumin) or large synthetic sugars

2. Fluids containing colloids will draw water out of both the intracellular and interstitial spaces to expand plasma volume

a) This is beneficial in hypovolemia or edema states

Crystalloid fluid types

Isotonic replacement solutions

1. Ringer's, Lactated Ringer's solution (LRS), Normosol-R

a) Components

(1) Isotonic fluid; approximately equal sodium (130-140 mEq/L) compared to normal plasma

(2) Inadequate amounts of potassium (only 4-5 mEq/L) for maintenance therapy

(a) Although normal plasma potassium hovers around 4 mEq/L, most of total body potassium is inside cells, and is not measured in the plasma

(b) Dogs normally lose 15–20 mEq/L of potassium per day in the urine

(c) When dehydration is present, the kidney will waste even more potassium in an effort to conserve sodium (via aldosterone release

(3) Therapy with LRS or Normosol alone can "wash out" intracellular potassium stores, especially in patients with polyuria, anorexia, vomiting, or diarrhea, and particularly in cats

(4) Buffered with lactate (LRS) or acetate and gluconate (Normosol-R)

b) Fluid distribution after administration

(1) Only one–third of given volume remains in vascular space; other two–thirds enters the interstitial space

c) Indications

(1) Good choice for shock with a colloid

(2) Good fluid for rehydration and diuresis

(3) When used for diuresis or maintenance therapy, should be supplemented with at least 20 mEq/L of KCl, unless animal is not producing urine, is Addisonian, or has an unresolved urinary obstruction

d) Contraindications

(1) LRS contains calcium – not the best choice in hypercalcemic patients

(2) Not ideal in patients with suspected metabolic alkalosis

(a) Metabolic alkalosis may occur with pyloric obstruction or some cases of gastric dilatation and volvulus

(3) Isotonic replacements fluids provide more than maintenance sodium – sodium load is often excessive for patients with hypertension, hypoalbuminemia, significant heart disease, hepatic insufficiency, or edema

2. Normal saline (0.9%)

a) Contains 154 mEq/L each of sodium and chloride; slightly higher in osmolality than LRS

b) Fluid distribution after administration

(1) Like LRS, about one third of given fluid remains in vascular space

c) Indications

(1) Reasonable choice for shock therapy

(2) Fluid of choice for hypercalcemia since it is calcium–free, and high sodium content will promote calcium loss in the urine

(3) Fluid of choice for hyperkalemia, since it is potassium-free

(4) Fluid of choice for sodium–depleted states

(a) Addisonian crisis

(b) Diabetic ketoacidosis

(i) Diabetic patients with ketoacidosis are almost always depleted in sodium and potassium

(ii) Unless diabetic patient is not producing urine, should always supplement 0.9% saline with at least 20–40 mEq/L of potassium chloride

(5) Fluid of choice for vomiting due to pyloric obstruction

(a) Saline plus potassium chloride can help resolve hypokalemic, hypochloremic metabolic alkalosis that results from loss of gastric acid

d) Contraindications and side effects

(1) Will exacerbate volume overload states

(a) Do not use in patients with significant heart disease

(i) Can lead to pulmonary edema

(2) Do not use in patients with hypoalbuminemia

(a) Liver disease

(b) Proteinuria/nephrotic syndrome

(d) Vasculitis

(i) Can lead to peripheral edema

(3) Do not use in patients with documented or suspected hypertension

(a) Cushing's syndrome

(b) Renal failure

(d) Hyperthyroid cats

Maintenance solutions

1. Half strength saline plus 2.5% dextrose

a) Components

(1) Isotonic fluid, but generates "free water" (water not associated with sodium or dextrose) after dextrose is metabolized

(a) This free water is more readily excreted by kidneys than is water that is associated with sodium

(2) Only contains 65–77 mEq/L of sodium

(a) This provides daily sodium requirements without sodium overload

(3) 2.5% dextrose (glucose) provides an insignificant amount of calories (85 kcal/L), but maintains isotonicity to plasma during administration

b) Indications

(1) Useful for patients with pre–existing sodium overload

(a) Diuresis of patients with heart failure and renal failure

(b) Diuresis of geriatric, hyperthyroid cats

(i) Important to also add potassium supplementation, since hypokalemia is common in liver failure

(2) Fluid therapy in patients with hypoalbuminemia, edema, or ascites

(a) Less likely to increase hydrostatic pressure or produce vascular volume overload

(b) Ideal in combination with a colloid such as Hetastarch

c) Contraindications

(1) Not the fluid of choice for hypovolemic shock

(a) Dextrose–associated water enters cells readily; does not stay in vascular space and therefore is poor at expanding blood volume

2. Plasma–Lyte 56®

a) Formulated as "ideal" maintenance fluids

b) Hypotonic to plasma

(1) May cause hyponatremia if given acutely in large volumes

c) Lower sodium content reflects amount required to replace daily sodium losses (40–60 mEq/L)

(1) Higher potassium content (13–20 mEq/L) also designed to match daily potassium losses

d) Indications

(1) For patients on long–term maintenance fluids (e.g. diuresis of renal failure, severe pancreatitis), these low sodium isotonic fluids are ideal, if they are available, for patients that cannot tolerate a sodium load

(2) For practical purposes, LRS, when supplemented with potassium, is a reasonable maintenance fluid in a patient who is able to handle sodium normally

(3) For other patients (heart failure, liver disease, hypertension, hypoalbuminemia, edema), 1/2 strength saline plus 2.5% dextrose, also with potassium added, is a very good alternative

Other crystalloids

1. 5% dextrose in water (D5W)

a) Is hypotonic to plasma and contains no sodium

b) Minor source of calories

(1) Contains 50 grams of glucose per liter, or only 170 kcals of carbohydrate energy per liter

c) Not suitable for sole maintenance therapy

(1) Will cause hyponatremia, hypokalemia, and hypochloremia with prolonged use

d) Not suitable for hypovolemic shock

(1) Only 8% of a given volume of D5W remains in blood compartment after IV administration

(2) Enters cells along with dextrose, under influence of insulin

e) Indications (not commonly used)

(1) Administration of drug infusions (dobutamine, doxycycline, dopamine)

(2) Therapy of severe refractory hypernatremia

(a) 0.9% saline, LRS, or half strength saline first

(b) D5W only if no response (uncommonly needed!)

f) Contraindications

(1) Do not give 5% dextrose (D5W) subcutaneously

(a) Can draw electrolytes from blood compartment and lower blood pressure

(b) Low pH can be irritating to tissues

(2) Do not use large volumes IV

(a) May cause hemolysis due to water entry into RBC's

(b) May cause cerebral edema due to movement of water into CNS

2. Hypertonic saline

a) 7.2% saline (8 times more concentrated than normal saline), indicated for small volume resuscitation of shock

(1) Developed for treatment of hemorrhagic shock in humans, since smaller volumes of fluid are more easily carried by paramedics

(2) Effective for treatment of shock in horses, cows, and other large patients

b) Advantages of hypertonic saline over isotonic fluids for hypovolemic shock

(1) More rapid response to resuscitation (almost immediate)

(2) Less risk of fluid overload

(3) Smaller volume necessary (more easily transported)

(4) Longer shelf–life

c) Indications

(1) Cerebral edema without intracranial hemorrhage

(2) Hypotension from GDV (accompanied with colloids)

(3) Not commonly used; colloids preferred in most instances

d) Administration

(1) 7.2% saline can be given through peripheral veins

(2) Suggested dose: 3 to 5 mls/kg IV as slow infusion over 5-10 minutes (can use buretrol to administer)

(3) Short acting

(a) Best combined with colloids for hypotensive shock

(4) Must follow with standard isotonic fluids to maintain perfusion and address any hypernatremia or hypokalemia

e) Side effects

(1) Transient ventricular arrhythmias

(2) May cause re–hemorrhage as blood pressure rises, if site of hemorrhage is not controlled

f) Contraindications

(1) Dehydration, cardiogenic shock, ketoacidosis

(2) Hypokalemia

(3) Active hemorrhage

(a) Monitor PCV and TP every 30-60 minutes initially; if >10% drop in PCV after hypertonic saline, look for site of hemorrhage

(4) Coagulopathy, thrombocytopenia

(5) Oliguric renal failure

Colloids

Advantages of colloids over crystalloid fluids

1. Exert oncotic pressure due to protein or large polysaccharide molecules that "hold water" in vascular space

2. Since almost all of administered fluid stays in vascular compartment, smaller fluid volumes are necessary to expand vascular volume

a) Less likely to cause hemodilution and hypoproteinemia

b) Less likely to cause fluid overload

Plasma

1. The ideal (most physiologic) colloid

2. Beneficial components of plasma

a) Albumin

(1) Exerts oncotic pressure

(2) Lasts one year or more in frozen plasma (even if not frozen immediately)

b) Coagulation factors

(1) Plasma must be used or frozen within 6–8 hours for clotting factors to be active

(2) Shelf life of coagulation factors in fresh frozen plasma stored in commercial freezer is 1 year

c) Antithrombin

(1) Natural anticoagulant produced by the liver

(2) Levels of antithrombin are often depleted in patients with liver failure, DIC, or protein–losing nephropathy

(a) This can lead to thrombosis or continued consumption of clotting factors

(3) Shelf–life of antithrombin in refrigerated plasma is about 6 weeks

d) Anti–proteases

(1) Alpha–1–protease inhibitor, alpha–2–macroglobulin may bind and/or inactivate circulating trypsin that is released during pancreatitis

3. Indications for plasma

a) Any hypoalbuminemic, volume depleted patient

(1) Best response in patients with:

(a) Temporarily impaired production of albumin (e.g. acute liver disease)

(b) Limited loss of proteins (surgery, trauma)

(2) In patients with ongoing loss of protein (e.g. glomerular protein loss or protein losing enteropathy), it is difficult to give enough plasma to appreciably raise plasma albumin levels

b) Can be used just prior to liver or kidney biopsy

(1) Will provide some albumin, maintain GFR, and provide antithrombin III to help prevent thrombosis

c) For pancreatitis

(1) May help prevent complications of hypoalbuminemia and DIC

(2) May control course of disease due to trypsin–binding activity of antiproteases

(3) However, plasma does not improve outcomes in controlled trials in humans with pancreatitis

d) In patients needing clotting factors

(1) DIC

(2) Warfarin and other anticoagulant rat poisons

(3) Von Willebrands disease, or hemophilia A or B

(a) Although cryoprecipitate preferred

4. Plasma dosage

a) 6 - 10 mls/kg (cats)

b) 10 - 20 mls/kg (dogs)

5. Limitations of plasmas

a) Hospital supply may be limited

b) Cost prohibitive to give multiple units for long term therapy

c) Must be thawed prior to use (no time in emergencies)

Hetastarch (hydroxyethylstarch)

1. Synthetic high molecular weight starch polymer (amylopectin) which exerts oncotic pressure

a) Formulated as 6% solution in saline

2. Long duration of action

a) Large molecules are slowly degraded by circulating amylase into smaller, osmotically active particles

3. Indications

a) Shock therapy, along with crystalloids

b) Intraoperative or postoperative fluid replacement where blood loss or lavage of body cavities has lead to protein loss and lowered plasma oncotic pressure

c) Hypovolemia with hypoproteinemia

(1) Post–operative abdominal surgery

(2) Protein–losing nephropathy

(3) Protein–losing enteropathy

(4) Vasculitis (preferred over plasma)

(5) Liver disease (if plasma unavailable)

(6) Sepsis (if plasma unavailable)

(7) Pancreatitis (if plasma unavailable)

4. Hetastarch dosage

a) 5 mls/kg over 5-10 mins for hypovolemia (cats)

b) 10– 40 mls/kg, (dogs); rate depends on severity of hypovolemia

c) CRI: 10 – 40 mls/kg/day

5. Side effects

a) Can overexpand blood volume if given too rapidly or in large volumes

b) Contraindicated in heart failure

c) May cause restlessness, salivation in some cats

Dextrans

1. Large synthetic sugars that exert oncotic pressure

a) Dextran 70

b) Dextran 40 (smaller particles)

c) Available as solutions in D5W or saline

2. Single infusion of dextrans can increase blood volume and improve hemodynamics for more than 24 hours in humans

3. Indications

a) Most criticalists use Hetastarch in preference to dextrans

b) Can be combined with hypertonic saline (e.g. Dextran 70 plus 7% NaCl) for rapid and sustained resuscitation of shock

(1) Dextran prolongs duration of hypertonic saline's effects on blood volume

(2) Possible uses: hemorrhagic shock, traumatic shock, surgical hypovolemia, septic and endotoxic shock, volume expansion in hypoalbuminemic patients

4. Dextran dosage

a) 5 mls/kg over 5-10 mins. (cats)

b) 10– 40 mls/kg (dogs); rate depends on severity of hypovolemia

5. Contraindications and side effects

a) Avoid use of Dextran 40 in patients with coagulopathies

b) Do not use in patients with heart failure, pulmonary edema, or cardiogenic shock

c) Avoid use of Dextran 40 in renal failure

(1) Decreased GFR may cause sludging of dextrans in renal tubules, with secondary obstruction and oliguria

d) Has been reported to cause anaphylaxis in humans

(1) Dextrans are potentially quite antigenic, however, newer formulations have had lower incidence of allergic reactions

e) May increase blood glucose (due to dextran metabolism)

f) May falsely elevate total protein as read on refractometer

g) May increase rouleaux formation and interfere with accurate blood cross matching

Oxyglobin (hemoglobin glutamer 200)

1. Contains purified bovine hemoglobin that has been altered by polymerization

2. Advantages over whole blood or packed red cells

a) Can be used immediately

(1) No cross match

(2) No warming required

b) No refrigeration needed and longer shelf life (2 years) than blood products

c) No risk of disease transmission

d) No need to maintain donor animals

e) No reported immune mediated transfusion reactions

f) Oxyglobin provides better oxygen delivery to microcirculation than erythrocytes

(1) Better perfusion with smaller oxyglobin molecule

(2) Improved off-loading of oxygen

3. Disadvantages of oxyglobin

a) Risk of volume overload, especially in cats!

b) Transient oxygen delivery effect (24-48 hours)

c) Plasma and tissue discoloration interferes with some serum chemistries and with clinical evaluation of mucous membranes

4. Indications

a) Traumatic hemorrhage with hypovolemia

b) Surgical blood loss

c) Severe anemia without cross-matched blood donor

d) Anemia with prior history of transfusion reaction

e) Hemolytic anemia

f) Methemoglobinemia (e.g. acetaminophen overdose in cats)

5. Dosage

a) 2.5 to 5 mls/kg (cats)

(1) Give slowly in cats (over 3-4 hours) to avoid volume overload and pleural effusion

b) 7.5 to 30 mls/kg total dose in dogs

(1) Do not exceed 10 mls/kg/hour in dogs

6. Side effects

a) Yellow-orange discoloration of mucous membranes

b) Brown (hemoglobin) discoloration of urine

c) Red discoloration of plasma (resembling hemolysis)

d) Signs of volume overload (vomiting, tremor, tachypnea, dyspnea, pleural effusion, pulmonary edema)

7. Contraindications

a) As for other colloids, do not use in patients with heart failure, pulmonary edema, or cardiogenic shock

b) Do not use in oliguric renal failure

c) Do not use if foil package has been open more than 24 hours (results in methemoglobin)

Table 1

Table 2