redazione@vetpedia.it +39-0372-40-35-36/37/47
  • Disciplina: Medicina d'urgenza
  • Specie: Cane e Gatto

Fluid therapy is the administration of crystalloids and colloids in order to maintain or restore homeostasis of water, electrolytes, acid-base state and perfusion. By correcting these imbalances, reduced oxygen availability (DO2) can also be treated and prevented. Fluid therapy can also be used solely for the administration of drugs.

Water is the solvent in which organic and inorganic solutes are dissolved and constitutes 60% of the body weight of an adult. The whole volume of water present in the body is called the ‘total body water’ (TBW): in dogs and cats under 6 months old and in obese patients, the TBW is reduced because adipose tissue contains less water than the lean mass. The daily water requirements of obese subjects should be calculated on the lean mass, multiplying the body weight by 0.7.1 The TBW of an animal is distributed in three compartments (Fig. 1):

  • intracellular: 67%;
  • interstitial: 25%;
  • intravascular: 8%.

Body fluids contain, besides water, cations (sodium, potassium, calcium, magnesium and other cations not usually measured), anions (chloride, bicarbonate and other anions not usually measured), proteins, inorganic acids and buffer systems. The distribution of these constituents varies depending on the compartment (Table 1).

Ions

Extracellular fluids

Intracellular fluid

 Intravascular        Interstitial   
 (mmol/L)                  (mmol/L)

(mmol/L)

CATIONS

Na+

K+

Ca2+  (ionised)

Mg2+(ionised)

 

TOTAL

 

ANIONS

Cl-

HCO3-

HPO4-,H2PO2-

proteins-

other

TOTAL

 

 

142.0

4.3

2.5

1.1

 

149.9

 

 

104.0

24.0

2.0

14.0

5.9

 

149.9

 

 

145.1

4.4

2.4

1.1

 

153.0

 

 

117.4

27.1

2.3

0.0

6.2

 

153.0

 

 

12.0

150.0

4.0

34.0

 

200.0

 

 

4.0

12.0

40.0

54.0

90.0

 

200.0

       

Table 1. Distribution of the electrolytes in the body’s fluid compartments.

The movement of water between the various compartments is influenced by the number of particles present and the electrical charge that they have. It is useful to know the concentration of these constituents in the extracellular compartment (extracellular fluid, ECF) in order to be able to choose the most appropriate fluid and thereby promote the movement of the constituents into the desired compartment.

 

DYNAMICS OF FLUID COMPARTMENTS


The distribution of fluids in the different body compartments is determined mainly by the equilibrium present between three pressures: oncotic, osmotic and hydrostatic and by other factors that regulate transvascular flow as represented by Starling’s equation:

V=[kf(Pc−Pif)−σ(μc −μif)]−Q                                                                        (1)

(V = volume filtered; kf = filtration coefficient; Pc = capillary hydrostatic pressure; Pif = interstitial hydrostatic pressure; μc = plasma oncotic pressure; μif = interstitial oncotic pressure; Q = lymphatic drainage from the interstitial space and of albumin towards the bloodstream; σ =diameter of the membrane pores)

From this formula it can be appreciated that transvascular flow (V), that is, the passage of water across the vessel wall, depends positively on the hydrostatic pressure (P) minus the oncotic pressure (μ) and increases as the coefficient of filtration increases. The hydrostatic pressure can be estimated indirectly from the systemic blood pressure: a rise in blood pressure causes an increase in hydrostatic pressure, while a reduction in blood pressure causes a decrease in P.

The osmotic pressure is the pressure produced by the number of particles within a solution2and it exerts its effect through an osmotic gradient; that is, the water necessary to equilibrate the number of particles on both sides of a membrane diffuses from the compartment with the lower concentration of particles into the compartment with the higher concentration. The volume of water shifted because of an increase or decrease in the number of particles corresponds to a measure of the osmotic pressure. The molecules responsible for osmotic pressure are small; those usually measured in order to calculate the osmolarity are sodium, glucose and urea, as indicated in the following formula:

Osmol = 2 x [Na+] + glucose (mg/dl)/18 + BUN (mg/dl)/2.8                                        (2)

(Osmol = osmolarity, [Na+] = concentration of sodium in the blood, BUN = blood urea nitrogen)

Osmotic pressure can also be measured using a specific instrument called an osmometer, which can be useful when imbalances in sodium must be treated.

According to the law of mass action, osmolarity must be maintained equal and constant within aqueous compartments separated by a semipermeable membrane: an increase in osmolarity is responsible for movement of water, which causes an increase of pressure. This pressure is called osmotic because it is produced by the solutes and created by the water. The osmotic pressure depends on the number of particles dissolved. In normal conditions the osmolarity of blood is about 300 mOsmol/L. The tonicity of a solution is the osmotic pressure of the fluid with respect to plasma. An isotonic solution therefore contains a similar number of molecules as that in plasma. The administration of an isotonic fluid does not cause changes in the osmotic pressure of the plasma. As indicated in equation (2), sodium is the molecule which contributes most to the increase in osmotic pressure and is the molecule present in greatest quantities in extracellular fluids (intravascular and interstitial). For this reason it is the ion with the highest concentration in balanced electrolyte solutions. Sodium, like other small molecules, crosses freely through capillary walls, dragging with it the water present in the intravascular space; this effect contributes to the movement of water from the intravascular compartment into the extravascular one. Sodium cannot pass freely through the cell wall, because its concentration within cells is regulated by the sodium-potassium pump (Fig. 2).

Hypotonic (unbalanced) solutions contain fewer osmotically active molecules than the number present in plasma. Thus, when such solutions are administered by intravenous or intraosseous infusion they cause a decrease in the osmotic pressure in blood and a rapid shift of free water into the extravascular space; the administration of excessive amounts of hypotonic solutions can, therefore, cause tissue oedema. Hypotonic solutions are used to administer free water quickly. In contrast, hypertonic solutions cause an increase in osmotic pressure, drawing water present in the interstitial and intracellular compartments into the intravascular compartment, producing a rapid expansion of circulatory volume. Hypertonic solutions must not be administered subcutaneously. The higher the tonicity of a solution, the greater the amount of water shifted and the faster its passage into the intravascular compartment. The effect of hypertonic saline solutions is transient and disappears within 2-4 hours because the water and electrolytes are quickly redistributed.

It is possible to hydrate a particular compartment by exploiting the different osmotic pressures of fluids. The restoration of normal water volume in a given compartment is called rehydration, while an excess of water is called oedema. When it is the extravascular space that must be rehydrated, crystalloid solutions should be given because by about 1 hour after administration 80% of the fluid has redistributed into the interstitial and intracellular compartments. If administered rapidly, crystalloid solutions also expand the circulatory volume, but only temporarily (the expansive effect lasts about 20 minutes - 1 hour) because the water in the solutions diffuses freely across the vessel walls. Glucose, which is also osmotically active although less effective than sodium, is present in numerous crystalloid solutions. Its osmotic activity lasts only a short time because it is rapidly broken down into water and carbon dioxide. The administration of a solution of 5% glucose in water is equivalent to giving free water with the risk of causing tissue oedema particularly if excessive amounts of the solution are infused. Glucose can be useful when drugs must be given with fluid therapy because it does not increase the tonicity of the blood. Hypertonicity could cause the patient’s blood pressure to rise as, for example, in congestive heart failure; in these cases, a solution of 0.45% NaCl + 2.5% glucose can be given to reduce the tonicity. The administration of solutions containing a high concentration of glucose (30-50%) causes a rapid but transient (about 20 minutes) expansion of the circulatory volume. The glucose contained in these high-concentration solutions is also metabolised very quickly and so excessive administration of these fluids can cause not only hyperglycaemia but also tissue oedema, like the isotonic 5% glucose solution. The solution is stabilised with hydrochloric acid and its pH is about 5.4.

The capillary oncotic pressure (COP) is the pressure exerted in the intravascular compartment by molecules that do not cross the capillary wall except after their breakdown. The COP contributes to the redistribution of water between the fluid compartments. The molecules responsible for the COP are the proteins contained in the plasma, the main one being albumin which alone contributes about 70% of the COP. Some starches, such as hydroxyethyl starches, and dextrans can also exert a positive oncotic pressure. The osmotically active molecules contribute to the shift of water into the intravascular compartment through the effect of the law of mass action, which, as in the case of oncotic pressure, maintains an equilibrium between the particles present on two sides of a membrane. The aqueous solutions with a high COP, called colloidal solutions or colloids, rapidly expand the circulatory volume, raising the COP of the blood. A reduction of the COP increases the passage of water from the intravascular space into the extravascular compartment, with the risk of tissue oedema.

Colloids must not be administered subcutaneously, but only by the intravenous or intraosseous route. These solutions are administered by slow, constant rate infusion (CRI) at 1-2 ml/kg/hour in order to maintain the COP within the normal range in cases of hypoproteinaemia (e.g., protein-losing enteropathies). In normal conditions the COP is about 20-25 mmHg. The administration of a colloid by a CRI or rapid infusion (boluses of 5-20 ml/kg i.v. in 15-20 minutes) should be considered when the concentration of serum albumin falls below 2.0 g/dl or the total protein concentration is less than 5.0 g/dl. To exert their effect, colloids must contain molecules greater than 35,000 Da in size so that the molecules cannot pass through the vessel wall. The so-called iso-oncotic colloids (e.g., 5% albumin)  have the same oncotic pressure as plasma, while hyperoncotic colloids (e.g., 25% albumin) have a higher COP. The administration of hyperoncotic colloids increases the COP very quickly and attracts water into the intravascular compartment equally quickly; these solutions must be used under close haemodynamic monitoring and in the case that albumin is used the patient must also be monitored for possible allergic reactions that the high concentration solutions can provoke.2 Colloids are used mainly to expand the circulating volume rapidly in order to restore the COP, and the transvascular movement of fluid governs the movement of albumin between the intravascular space and the extravascular one (see albumin).

 

HYDRATION AND PERFUSION


A patient’s state of hydration and perfusion must be assessed in order to determine the amount of fluid to infuse and the rate at which it should administered.3 The state of hydration can be evaluated clinically or determined by measuring the concentration of sodium [Osmotic gap = equations (4) and (5)]. Some signs that indicate the severity of dehydration can be detected clinically (Table 1).

Percentage of dehydration

Clinical signs

<5

Skin within the norm and other signs of dehydration not clinically detectable

5 – 6

Reduction of skin elasticity, dry mucosae

6 – 8

Delayed recoil of a skin fold, slight increase in capillary refill time, plus the above signs

10 – 12

Skin remains in a fold, weak pulse, sunken eyes, impaired perfusion, plus all the above signs

12 – 15

Uncompensated hypovolaemic shock, life-threatening

Table 1. Dehydration and clinical signs.

States of dehydration of less than about 5% are not clinically detectable. The percentage of dehydration estimated from clinical signs must be multiplied by the patient’s weight to obtain the amount of water lost which needs to be replaced by fluid therapy, as indicated in the following equation:

Weight in kg x % dehydration = Litres of fluid to reintegrate                                    (3)

If the fluid loss has been acute, the replacement must be rapid, within 4-12 hours; vice versa, if the fluid loss is chronic, the replacement can be carried out over 24 hours. In order to quantify a patient’s dehydration by using the calculated osmolarity, the osmolar gap must be determined as follows:

first the patient’s osmolarity is calculated using the equation below:

2(Na++K+) + BUN/2.8 + Glucose/18 = mOsmol/L                                               (2)

then the osmolar gap is calculated  as indicated:                                                 

Osmolpatient - Osmolnormal = Osmolar gap                                                        (4)

Finally, the percentage dehydration can be determined:

Osmol gap/ Osmol normal = % dehydration                                                          (5)

For example, for a 10 kg dog with a calculated osmolarity of 335 Osmol/l,

  • 335 - 310 = 25 mOsmol (osmolar gap)
  • 25/310 = 0.081 = 8.1% (percentage of dehydration)
  • 10 kg = 10,000 ml x 0.081 = 810 ml (replacement volume)

The volume of fluids to infuse each day to the patient is determined by the sum of the replacement volume necessary to resolve the dehydration plus the amount of water used to maintain bodily functions (maintenance volume) and any water lost because of an ongoing pathological process (e.g., vomiting, diarrhoea, polyuria). The maintenance volume is calculated using the following equation:

30 x kg + 70 = maintenance volume (ml)                                                  (6)

The volume calculated with equation (6) must be divided by 24 to obtain the volume of fluid (in ml) to infuse per hour, as shown in equation (7).

              Maintenance volume/24 = infusion rate of the maintenance volume (ml/h)        (7)

The volume of fluids lost is calculated by summing the amount lost in each episode. For example, if an animal vomits five times in a day, and each time expels 30 ml of material, the volume of fluids lost to include in the calculation of daily fluid requirements is 150 ml/day.

The total volume to infuse each day is calculated using the following equation:

Maintenance volume + replacement volume + fluids lost                              (8)

When the patient has been rehydrated, for example the day after starting the fluid therapy or 4 hours after if the volume has been replaced more rapidly, it will be given only the maintenance volume shown in equation (6); only if fluid is still being lost is the volume of fluids lost added to the maintenance volume.

Dehydration can be classified on the basis of its tonicity, which is determined from the concentration of the fluid remaining within the body and not from the fluid lost:

  • isotonic: when the values of Na in the blood are between 140 and 150 mEq/L in the dog and between 150 and 160 mEq/L in the cat;
  • hypotonic: when the values of Na in the blood are <140 mEq/L in the dog and <150 mEq/L in the cat; this can occur, for example, in patients with diarrhoea, vomiting, congestive heart failure, or nephrotic syndrome, with loss of extracellular fluid;
  • hypertonic: when the values of Na in the blood are >150 mEq/L in the dog and >160 mEq/L in the cat; this is rare and is caused by the loss of pure water or water loss when there is an excess of solutes in the serum; in the dog it can be caused by loss of pure water in the form of water vapour in some cases of hyperventilation.

The amount of sodium present in the serum is influenced by the cells’ capacity to transport it towards the interstitial compartment; this transport is regulated by the activity of the sodium-potassium pump, which is ATP-dependent. All pathological processes that reduce the production of energy in the mitochondria (e.g. hypoxia) are associated with a flow of sodium (and, therefore, water) into the intracellular compartment, where it can cause oedema and cell death.

The assessment of tissue perfusion provides information useful for deciding the rate of infusion needed. When perfusion is impaired, the blood supply to tissues is reduced and, therefore, tissue oxygenation, nutrient supply and removal of catabolites from the cells are also reduced. A severe impairment in perfusion that is protracted over time can cause decompensated shock and the patient’s death. 

The parameters useful for assessing perfusion are:

  • heart rate and pulse (dangerous if  >200 or <60 in the dog, >260 or <150 in the cat)
  • colour of the mucous membranes (white: anaemia, decompensated shock; blue: cyanosis; brown: methaemoglobinaemia; petechiae: coagulopathy; brick red: hyperdynamic state, peripheral vasodilatation)
  • capillary refill time (<1 second: hyperdynamic state or peripheral vasodilatation; >2 seconds: insufficient perfusion);
  • arterial  blood pressure (systolic >100 mmHg, better if the mean is >80 mmHg);
  • urine output (≥1-2 ml/kg/hour);
  • blood lactate levels (normal values 0.5-2.5 mmol/L)

When more invasive monitoring is possible, the following parameters can be measured to collect objective data:

  • cardiac output;
  • oxygen availability (DO2);
  • oxygen consumption (VO2);
  • central venous haemoglobin oxygen saturation (SVO2);
  • peripheral vascular resistance;
  • central venous pressure;
  • invasively measured arterial blood pressure.

Hypovolaemic patients in whom good organ perfusion cannot be ensured must be given a rapid infusion of fluids capable of restoring an effective circulatory volume (resuscitation fluid therapy). The fluids commonly used for fluid therapy are classified on the basis of their composition into crystalloids and colloids.

 

CRYSTALLOIDS


Crystalloids are aqueous solutions containing small, osmotically active molecules, have an osmotic pressure similar to that of plasma (about 300 mOsmol/L) and can cross the vessel wall. They are divided into balanced and unbalanced solutions. The balanced solutions, also called reintegration fluids, have an electrolyte concentration similar to that of extracellular fluid; the unbalanced solutions, also called maintenance fluids, may contain electrolytes and glucose or only glucose. The balanced solutions are useful for replenishing lost fluids, while the maintenance solutions are used to infuse free water, to maintain hydration in patients unable to drink, or to administer drugs. The choice of the most appropriate fluid depends on the electrolyte and acid-base status of the patient, in that crystalloids have different electrolyte concentrations, different pH values and different buffer system precursors (e.g. sodium bicarbonate). Crystalloids are used to replace water or maintain hydration of the extravascular compartment. They can also be used to restore an effective circulatory volume, thus acting as resuscitation fluid therapy: boluses of 20 ml/kg are administered intravenously every 15-20 minutes up to a maximum of four boluses in dogs and three in cats. Colloids can be given together with crystalloids during resuscitation fluid therapy. In this case the dose of both should be reduced according to the following equation:

Crystalloids 10-30 ml/kg i.v. + Colloids 5-15 ml/kg i.v.                                                    (9)

When the perfusion parameters (at least heart rate, characteristics of the pulse, capillary refill time, arterial blood pressure and body temperature) are within the normal range, the rate of crystalloid infusion should be reduced to a maintenance level, calculated using equation (7), otherwise there would be a high risk of tissue oedema (particularly pulmonary oedema), haemodilution and reductions in the concentrations of haemoglobin and clotting factors. It is good practice to measure at least the haematocrit and concentration of total proteins before and after the administration of crystalloids in order to monitor the haemodilution.3,5 Crystalloids have different compositions, as shown in Table 2.

CRYSTALLOIDS

Solution

pH

Na

Cl-

K+

Ca++

Mg+

Osmol/l

kcal/l

Buffer

mOsmol/l

Sodium chloride 0.9%

5.0

154

154

0

0

0

308

0

 

Lactated Ringer’s solution (LRS)

6.5

131.5

111.5

5.5

3.5

0

279

0

Lactate 29

Electrolyte reintegration with sodium gluconate

5.5-7.0

140

98

5.0

0

3

 

 

Gluconate 23

Acetate 27

Plasmalyte A

7.4

140

98

5.0

0

308

312

0

Lactate 8

Acetate 47

Electrolyte rehydration III

5.5

140

103

10

5

3

306

0

Acetate 47

Ringer’s acetate

6.4

132

109.5

4

3

0

276

0

Acetate 29.5

Glucose 5%

4.0

0

0

0

0

0

252

170

0

Glucose 2.5% + ½ strength LRS

5.0

65.5

55

2

1.5

0

263

89

Lactate 14

Glucose 20%

4.0

0

0

0

0

0

1112

800

0

Glucose 50%

4.2

0

0

0

0

0

2780

1700

0

NaCl 7%

5.0

1197

1197

0

0

0

2394

0

0

Table 2. Composition of the most widely used crystalloids.

The hypertonic crystalloids rapidly expand the circulating volume drawing water from the extravascular space (interstitial and intracellular) into the intravascular compartment. This is a short-lasting effect, present for about 2-4 hours. The dose required is 2-4 ml/kg given as an intravenous bolus. By increasing the circulating volume, the cardiac output and systemic blood pressure are also increased. These solutions are, therefore, particularly indicated in resuscitation fluid therapy and in patients with head injuries to reduce cerebral oedema. The hypertonic crystalloids improve blood flow in the microcirculation as a result of reductions in the size of endothelial cells and the viscosity of the blood. The expansion of the circulatory volume usually disappears within about 4 hours following redistribution of the fluid. However, to increase the expansive effect and its duration, crystalloid solutions are often diluted with colloids (e.g. dextran 70 and  hydroxyethyl starches) forming the so-called “rescue solutions”. Given the possibility of administering small volumes of hypertonic saline solutions these solutions are also used in large animals and in heart surgery to avoid the oedema that would occur with fluid therapy with isotonic crystalloids.

After administering hypertonic saline solutions (3 – 7.5%) the patient’s electrolytes should be measured to monitor the development of any side effects, such as hypernatraemia, hyperchloraemia and hypokalaemia. Side effects are usually transient. Rapid infusions can cause ventricular arrhythmias and haemodilution and hypertonic saline solutions are obviously contraindicated in hypernatraemic patients. They must be used in severely dehydrated patients with great care and combined with fluid therapy with isotonic crystalloids to avoid cellular dehydration and potentially severe complications. Hypertonic crystalloids, such as 0.45% NaCl solution and 2.5% glucose solution, are usually mixed to obtain a single solution with a normal osmolarity but with a low content of sodium, in order to reduce fluid retention, which is particularly contraindicated in patients with heart disease or liver failure. These solutions are also used to treat hypernatraemia.

 

COLLOIDS


Colloids are aqueous isotonic solutions that contain molecules with oncotic activity because the molecules are larger than the pores of the capillary walls. Colloids attract water into the vascular compartment through the effect of the osmotic  gradient and electro-neutrality since the molecules in colloids have a negative charge and, therefore, attract cations and water.4 Since an infusion of colloids causes expansion of the circulatory volume, these solutions are also called plasma expanders. The expansion is rapid and its duration depends on the type of colloid used and the conditions of the vessel wall. For example, in systemic inflammatory response syndrome (SIRS) the pores in the vascular wall become enlarged and the expansion of the circulatory volume and the increase in COP are altered; given that it is not possible to predict the duration of the volume expansion, in these cases it is important to monitor haemodynamic parameters closely (at least systemic blood pressure and indicators of perfusion). The efficacy of a colloid and its duration of effect depend on its capacity to form bonds with water molecules and its rate of breakdown.6 Rapid expansion of the circulatory volume improves tissue perfusion and mean blood pressure in hypotensive and underperfused patients and in those with hypovolaemic and distributive shock. Colloids are, therefore, indicated in cases of hypoproteinaemia, hypoalbuminaemia, haemorrhage, fluid effusions into the third space, trauma, sepsis, burns and hypotension.

The daily dose of colloids is 10-20 ml/kg i.v. If a CRI is used, the rate should be 1-2 ml/kg/hour, again administered intravenously. A CRI is used when it is necessary to increase the COP in cases of hypoproteinaemia. In the dog, a dose of 10-20 ml/kg/day can be given as a rapid bolus injection (or with an infuser) if effective circulation must be restored, whereas the dose in the cat, which is particularly sensitive to colloids, is 5 ml/kg in intravenous boluses over 15-20 minutes. If these fluids are administered more rapidly, the patients can develop tremors of striated muscle and central nervous system excitation. Excessive use of colloids can cause haemodilution (particular care must be taken in anaemic subjects), prolongation of clotting times, due to dilution of clotting factors, and pulmonary oedema. The administration of colloids does not exclude the contemporaneous administration of crystalloids although in this case the doses of both should be reduced, as shown in equation (9).

Colloids can be divided into natural and synthetic fluids. The former include plasma, whole blood, gelatine, red blood cell concentrates, polymerised haemoglobin and human albumin. The products of natural origin can cause hypersensitivity reactions and transmit infectious diseases. The most widely used synthetic colloids are the hydroxyethyl starches and dextrans. Table 2 presents the most commonly used colloids.

COLLOIDS

Solution

pH

Na

Cl-

K+

Ca++

Mg+

Osmol/l

Kcal/l

Buffer

mOsmol/l

COP

mmHg

Duration

hours

Tetrastarch 6%

3.5-6.0

154

154

0

0

0

308

0

0

25

4-6

Hetastarch 6%

5.5

154

154

0

0

0

310

0

 0

32

24

Pentastarch 6%

3.5-6.0

154

154

0

0

0

308

0

 0

25

5

Dextran 40

3.5-7.0

154

154

0

0

0

255

0

0

40

12

Dextran 70

5.1-5.7

154

154

0

0

0

310

0

0

60

24

Gelatine

7.2-7.3

145

145

5.1

6.26

0

310

0

0

25

2-4

Succinyl gelatine

7.4

154

125

0,4

0,4

0

279

0

Nd

n.d.

2-4

Human albumin 5%

Nd

152

nd

0

0

0

nd

 

20

20

24

HBOC

7.8

150

118

4

1.4

0

300

0

Lactate 28

37

24

Plasma

7.4

145

105

5

5

3

300

 

Bicarbonate 24

17-20

24

Table 2. Colloids (COP = oncotic pressure, HBOC = haemoglobin-based oxygen carrier or bovine polymerised haemoglobin).

The hydroxyethyl starches are derivatives of amylopectin that has been hydroxylated (addition of -OH hydroxyl groups) to prolong its half-life since serum amylases degrade amylopectin very quickly. The number and position of the –OH groups on the amylopectin molecules and the molecular weight of the compounds in the solution influence the potency and duration of the effect. The degree of branching of molecules of hydroxylated amylopectin can be between 0.4 and 0.8; optimal values are around 0.4. The C2/C6 substitution ratio, determined by the position of the –OH groups, also influences the time the solution remains in the circulation and the duration of its effect; the optimal ratio is around 4 to 5. Likewise, the molecular weight (Mw) modifies the effect of the water attraction and the half-life of the solution; the Mw varies from 130,000 Da to 450,000 Da. Hetastarch has a half-life of about 24 hours, whereas the half-lives of tetrastarch and pentastarch are about 4-6 hours. The maximum daily dose is approximately 20 ml/kg/day. Colloids, particularly when given at high doses, can increase the prothrombin time and partial thromboplastin time.

Dextrans are aqueous solutions containing high molecular weight polysaccharides derived from the fermentation of glucose; these polysaccharides have fewer branches than the hydroxyethyl starches. There are two types of dextrans on the market: dextran 40, which has a Mw of 40,000 Da and exerts an oncotic pressure of 40 mmHg, while dextran 70, with a Mw of 70,000 Da, exerts an oncotic pressure of about 60 mmHg. Dextrans are metabolised by numerous organs at a rate of 70 mg/kg/24 hours.3 The effect of dextran 70 lasts about 24 hours while that of dextran 40 lasts about 2.5 hours. The dextrans are filtered freely through the renal glomeruli and enter the tubules where they can precipitate causing acute renal failure due to obstruction of the tubules. This phenomenon occurs mainly in dehydrated patients and in those with pre-existing renal disease. Dextrans have positive rheological properties, reducing adhesion between cell surfaces, improving the microcirculation during impaired perfusion and lowering the risk of thrombosis in states of hypercoagulation. The daily dose is 10-20 ml/kg administered intravenously.

The characteristics of plasma are influenced by its protein content. This natural product is species-specific. It is separated from the blood by centrifugation and marketed fresh or frozen. In the former case the plasma contains all the clotting factors, whereas in the latter case it contains only the thermostable ones. Both fresh and fresh-frozen plasma are used mainly when it is necessary to replace clotting factors in consumption coagulopathies. Plasma can also be used to treat hypoproteinaemia, but in this case large quantities are needed which increases both the risk of hypersensitivity reactions and costs. It has also been used in the management of SIRS, disseminated intravascular coagulation and pancreatitis. 

Human serum albumin is obtained from a pool of human donors and is available at concentrations of 5% and 25%. The former exerts an oncotic pressure similar to that of blood (20 mmHg), while 25% albumin exerts a pressure of about 70 mmHg. Albumin can be diluted in physiological saline, Ringer’s lactate, or 5% glucose solution. Albumin is the protein found in greatest quantities in the blood. It has a molecular weight of about 65,000 Da and is responsible for about 70% of the COP. It, therefore, plays a fundamental role in the distribution of fluid between compartments. A fall in the COP can produce tissue oedema and cell death. Besides contributing to maintaining COP, albumin has numerous other activities: it transports drugs, electrolytes, hormones, lipids and metals, removes superoxide radicals, inflammatory molecules, cations and anions, increases redox potential thus protecting the cell wall from reperfusion injury, and inhibits xanthine oxidase, which is responsible for cell death in the terminal stages of shock. Albumin is also present in the extravascular space, but at a lower concentration, thus creating an osmotic gradient and movement of albumin between the two compartments. The rate of this movement, called the transcapillary escape rate (TER) is influenced by the concentration of albumin in the plasma, by the permeability of the walls of the microcirculation and by the movement of solutes and electrolytes (positive and negative charges). When the TER is altered by syndromes such as SIRS (e.g. hypoalbuminaemia in parvovirus-induced gastroenteritis) human serum 5% albumin can be administered as a CRI at 2 ml/kg/hour for a total dose of 20 ml/kg/day in order to restore the COP and perfusion. At this rate the total amount can be infused in about 10 hours, during which there may be improvements in the TER and indicators of perfusion. Furthermore, at this rate, the author of this article never encountered life-threatening hypersensitivity reactions in dogs or cats, even when 5% albumin was infused into the same patient for several days.2 Although the most common side effect is haemodilution, patients should be monitored to detect the appearance of any signs of allergic reactions as early as possible; these signs include tremors, urticaria, anaphylaxis, sialorrhoea, hyperthermia and diarrhoea. The daily dose of human serum 5% albumin should not exceed 20 ml/kg i.v. in order to avoid hypersensitivity reactions and the rate should not be faster than 2 ml/kg/hour.

Solutions containing gelatine, for example succinyl gelatine or modified fluid gelatine, produced by thermal hydrolysis of bovine bone collagen, have a reticulated structure with urea bridges. The molecular weight of gelatines is about 3000 Da. Their plasma-expanding effect lasts about 2 hours. They cause allergic hypersensitivity reactions more frequently than dextrans. The dose for expansion of the circulatory volume is 20 ml/kg/day i.v.

Polymerised haemoglobin of bovine origin (a haemoglobin-based oxygen carrier, HNOC) has two fundamental characteristics: it is smaller than normal haemoglobin, thus diffusing better in poorly perfused or partially obstructed tissues, and it has a lower affinity for oxygen, thus releasing oxygen more readily into the tissues. It has an osmolarity of about 300 mOsmol/l, a molecular weight of 65,000-130,000 Da and a pH of 7.8. It acts as a plasma expander and an oxygen carrier. HBOC has a COP of about 20-25 mmHg and its effect lasts about 24 hours. Following its administration the serum becomes reddish coloured which hampers the reading of biochemical tests and measurement of the haematocrit. Values of the haematocrit measured after administration of an HBOC do not reflect any increases because the haemoglobin molecules in the HBOC cannot be determined by a blood cell analyser or refractometer. The administration of 15-30 ml/kg increases the haemoglobin concentration by 2.5-4 g/L. HBOC is stable at room temperature for about 3 years and cross-matching tests are not required for its administration in either dogs or cats (or indeed in exotic animals). Once the packaging has been opened, an HBOC must be used within 24 hours. These products are indicated for the management of anaemia, haemorrhage, hypovolaemic shock and ischaemia. Jaundice and haemoglobinuria may occur after the administration of an HBOC. The dose is 10-30 ml/kg/hour i.v. (in the case of severe haemorrhage it can administered several times up to a dose of 40 ml/kg/day). It is not available in Italy.

The diagram below summarises the methods of administering fluids.

                                      

References


  1. Wellman ML, DiBartola SP, KohnCW. Applied physiology of body fluids in dogs and cats. In Di Bartola SP ed. Fluid electrolyte and acid-base disorders in small animal practice. St. Louis: Saunders, Elsevier; 2006, pp.3-25
  2. Vigano’F, Perissinotto L, Bosco V. Administration of 5% human serum albumin in dogs and cats. J Vet Emerg Crit Care 2010; 20(2):237-243
  3. Tonozzi C, Rudloff E., Kirby R.Perfusion versus Hydration: impact on the fluid therapy plan. Compend Contin Educ Vet 2009;31(12):E1-E14
  4. Chan DL, Rozanski EA, Freeman LM, Rush JE, Colloid osmotic pressure in health and disease. Compend Contin Educ Pract Vet. 2001; 23(10):896-904.
  5. Viganò F. Fluidoterapia. In F. Vigano’ Ed. Medicina d’urgenza e terapia intensiva del cane e del gatto, Milano/Cremona Masson/E.V. S.r.l.; 2005, pp. 50-62.
  6. Chan DL. Colloids: current recommendations. Vet Clin North Am Small Anim Pract 2008 May;38(3):587-93,xi.