A refresher on IV fluid therapy (Proceedings)

Fluids are divided into two main groups: crystalloids and colloids. Crystalloids contain solutes (variable amounts of electrolytes), water and may contain dextrose. They distribute throughout the extracellular fluid compartments rapidly, and will slowly equilibrate with the intracellular fluid compartments. They are characterized based on their tonicity (isotonic, hypotonic, hypertonic) and by their effects on acid-base status (alkalinizing or acidifying). Colloids contain large molecules that cannot (or slowly) escape from the intravascular space, thus, they have a smaller volume of distribution compared to crystalloids. The colloids are classified based on their origin (synthetic vs. natural).

Isotonic crystalloid solutions:

All of these solutions are approximately isosmolar to blood and replace electrolytes as well as water. Their volume of distribution is predominantly the extracellular space. Following administration of a crystalloid bolus, 65-75% of that fluid will leave the intravascular space and redistribute to the interstitial space within 30 minutes. This is the basis for the 3:1 rule (replace 1 part blood lost with 3 parts crystalloid). Clinical indications for isotonic crystalloid therapy are many, but the most common uses are shock resuscitation, rehydration and replacement of isotonic losses.

0.9% NaCl: This is considered an acidifying solution, but not just because it has an acidic pH. The acidifying effects are due to the high chloride concentration (154 meq/L) compared to plasma (110 meq/L) which will, over time, create hyperchloremia and thus acidosis. Because of it's high chloride and sodium content compared to plasma (see table below), it is considered the fluid of choice for Addisonian crisis and hypochloremic metabolic alkalosis (as occurs with upper GI obstruction). It is often used in management of the DKA patient as those patients are usually total body sodium depleted.

Normosol-R and Plasmalyte 148: These similar buffered solutions are considered alkalinizing as they both contain acetate and gluconate, which are broken down by a number of tissues to bicarbonate. These have similar electrolyte compositions and contain magnesium. There are no specific indications or contraindications for use of either, although research has shown that rapid blousing of acetate containing solutions in animals at a deep plane of anesthesia caused temporary hypotension.

Lactated Ringer's Solution (LRS): This is an alkalinizing solution that uses lactate as the bicarbonate precursor, a process that occurs in the liver. Therefore, end-stage liver disease is a potential contraindication as hyperlactatemia could result. LRS has the lowest osmolarity and lowest sodium concentration (130 meq/L) compared to other isotonic crystalloids. The only major contraindication for use of LRS is in-line (i.e., via the same catheter) administration with blood products. The calcium in LRS will chelate the anticoagulant in the blood products and could lead to thrombosis.

A common question is: which isotonic crystalloid is the best for the shocky patient? Millions of dollars and decades of research have been performed to answer this question. The answer is… they are all pretty much equivalent.

Hypotonic crystalloids

Examples of these include 5% dextrose in water (D5W), 0.45% NaCl (½strength), 0.45% NaCl with 2.5% dextrose (½ and ½) and Normosol-M. While some of these solutions (D5W, ½ and ½) are similar in osmolarity to blood, they are considered hypotonic solutions. This is because the dextrose is rapidly taken up by the cells, leaving a hypotonic solution. Hypotonic crystalloids rapidly redistribute within the total body water, leaving very little in the intravascular space. These fluids are used for replacing a free water loss (hypernatremia) and for maintenance fluid therapy. They should never be used for fluid resuscitation from shock, as they do not provide meaningful expansion of the intravascular volume.

0.45% NaCl (with or without dextrose): These fluids are used for maintenance fluids, or to expand free water (for the hypernatremic patient). They can also be used for patients with end-stage renal or heart failure, as they contain lower sodium concentrations (77 meq/L) and may help to prevent volume overload. They may also be used for patients receiving bromide therapy. Higher chloride containing solutions can decrease bromide levels through decreased renal retention of bromide.

5% dextrose in water: Since D5W is basically sterile water, this fluid is normally used to replace free water in the hypernatremic patient. Care should be used to not decrease sodium concentrations faster than 0.5-1.0 meq/hr as neurological sequealae may develop. D5W contains only 170 kcal/L from dextrose, and is not sufficient to meet energy requirements. For example, an average sized cat requires 220 kcal/day and would need almost 1.3L/day, or 54 ml/hr, to meet its RER.

Normosol-M: This solution is similar to Normosol-R in that it contains magnesium, and utilizes acetate and gluconate as buffers. It also has 13 meq/L of potassium, which could cause cardiovascular problems if large amounts are rapidly bloused. It is intended for maintenance fluid therapy once replacement requirements have been met.

Hypertonic solutions

7% NaCl (HTS – hypertonic saline) is used for rapid expansion of the intravascular volume. HTS pulls fluid primarily from the interstitial compartment. The advantage is that only small volumes are required to increase intravascular volume quickly. Its use is primarily for treatment of the head trauma patient and in shock resuscitation. Anti-inflammatory effects have also been documented. The volume expansion provided by HTS is short lived, as the sodium redistributes throughout the extracellular compartment quickly. HTS is available as both 7-7.5% and 23% solutions. The 23% solution MUST be diluted prior to administration. HTS should be administered no faster than 1ml/kg/min as vagally mediated bradycardia or arrest could occur.

Synthetic colloids

6% Hetastarch (HES) and Hextend: Both are made with hydroxyethyl stach, a polydispersed starch complex. Hetastarch is dissolved in 0.9% NaCl, while Hextend is dissolved in modified LRS. The volume of distribution is primarily within the intravascular space, depending on the vascular permeability. Administration increases intravascular volume by 1-1.4x, and the duration of action is almost 24 hours. Indications include volume resuscitation and oncotic support for hypoprotenemia. At doses greater than 20 ml/kg/day, a dose dependent coagulopathy has been reported. However, this has not been shown to increase risk of clinical bleeding in veterinary patients.

Voluven: For a period of time, HES was pulled from the market due to the above mentioned coagulopathy. Voluven is another form of HES with a lower C2:C6 substitution ratio. This reduces the likelihood of coagulopathy even with doses greater than 20ml/kg/day. The cost per 500ml bag is $44, compared to Pentastarch at $62/bag.

Natural colloids

Plasma and whole blood can provide clotting factors and albumin. If treating for severe hemorrhage, RBC products should be used in a 1:1 ratio with plasma. The dose for hemorrhagic shock is 20-30 ml/kg, which can be cost prohibitive in all but the smallest patients.

Human Albumin (HA): Is used to increase oncotic pressure. Albumin distributes throughout the extracellular fluid volume, so relatively large doses must be given. Initially, administration of HA results in an increase in intravascular volume of 3-5x until redistribution occurs. It has not been proven to be superior to isotonic crystalloids for shock resuscitation. Its use in veterinary medicine is controversial due to transfusion and delayed immunologic reactions.

What route of delivery should be used?

The intravenous route should be used for all patients with: cardiovascular compromise or shock, moderate to severe dehydration, or for patients with significant ongoing losses.  If venous access cannot be obtained (especially in small/pediatric patients), the intraosseus route can be used, or a vascular cutdown can be performed. The subcutaneous route should not be used in the shocky patient as peripheral vasoconstriction will severely limit absorption. In the mildly dehydrated patient, the subcutaneous route is sufficient.

How fluid should be given, and how fast?

The three phases of fluid delivery are resuscitation, replacement and maintenance.

The resuscitation phase is the rapid restoration of intravascular volume by administration of intravenous fluids. This is used to address hypovolemia, and is not required in all patients. Signs of hypovolemic shock, such as tachycardia (bradycardia in the cat), pale mucous membranes, altered mentation, cool extremities and poor pulses, indicate the need for resuscitation. For isotonic crystalloids or colloids, the shock doses should be divided into aliquots of 1/4 to 1/3 of the total volume and repeated as needed to resolve signs of shock. Shock doses are listed below:

Fluid type Shock dose Aliquot amount Isotonic crystalloid 80-90 ml/kg (dog); 40-60 ml/kg (cat) 10 ml/lb (dog); 10 ml/kg (cat) Synthetic colloid 20 ml/kg (dog); 10-20 ml/kg (cat) 5 ml/kg (dog); 2.5–5 ml/kg (cat) Hypertonic Saline 4-6 ml/kg 4-6 ml/kg

Once shock signs are alleviated, as evidenced by normalization of heart rate and pulse quality, improved mentation, pinker mucous membranes, and reduction in lactate concentrations, resuscitation therapy should cease. Shock doses should be given over a 15-20 minute period, reassessing the patient after each aliquot is given

The replacement phase is aimed at replacing the extravascular volume lost during fluid shifts that occur to maintain intravascular volume. Fluid losses, such as those that occur with vomiting, diarrhea, renal disease and excessive insensible losses will initially lead to dehydration (loss of TBW), and finally to signs of hypovolemia. Again, if signs of hypovolemia are present, fluid resuscitation should precede replacement. Isotonic crystalloids should be used for replacement. Clinical signs of dehydration include tacky mucous membranes, decreased skin turgor, sunken eye position within the orbit, and prolonged CRT. Signs of hypovolemia are almost always present in patients with >10% dehydration. To calculate dehydration, the estimated percent dehydration should be multiplied by body weight (in kg) to estimate the replacement amount in liters. This should be replaced over 8-24 hours. After replacing the estimated replacement amount, the patient should be re-assessed and fluid requirements recalculated. Fluids should always be titrated to effect. Replacement fluids should also be used for ongoing fluid losses. Ongoing losses can be estimated by weighing diarrhea or vomitus. Daily fluctuations in body weight can be very useful indicators of fluid status.

Maintenance fluids are based on the physiological fluid requirement. There are multiple formulas to calculate maintenance requirements, but allometric scaling best predicts fluid requirements in very small and very large patients. Formulas include:

• (30 x BW in kg) + 70 = ml/day

• 132 x BW0.75 = ml/day (dogs)

• 70 x BW 0.75 = ml/day (cats)

The choice of crystalloid fluids depends on the volume status and electrolyte concentrations of the patient. Hypotonic crystalloids can be used as indicated, especially in the hypernatremic or hyperchloremic patient.

0.9% NaCl

Normosol R

Plasmalyte-148

LRS

0.45% NaCl

0.45% NaCl + 2.5% Dextrose

5% Dextrose in water

7% NaCl

Tonicity

Iso

Iso

Iso

Hypo

Hypo

Hypo

Hyper

Osmolarity

308

294

278

154

297

287

2396

Na

154

140

130

77

77

-

1198

Cl

154

98

109

77

77

-

1198

K

-

5

4

-

-

-

-

Mg

-

3

-

-

-

-

-

Ca

-

-

3

-

-

-

-

pH

5.5

7.4 – 5.5

6.5

5.5

5.5

5.0

Buffer

-

Acetate

Gluconate

Lactate

-

-

-

-

Special Indications

Addisonian crisis

Metabolic alkalosis

DKA

Heart failure

End-stage renal failure

Bromide therapy

Free water replacement

Free water replacement

Head Trauma

Low volume resuscitation

Contra-indications

Hyperchloremia

Severe acidosis?

Rapid boluses under anesthesia?

Liver Disease?

In-line blood transfusions

Resuscitation

Replacement

Severe dehydration?

Indications

Resuscitation

Replacement

Rehydration

Hypernatremia

Maintenance Fluids

Resuscitation