Plasma Volume Expanders

Background

Maintaining the correct fluid balance is an important part of treating patients in surgical procedures where there is blood loss or in trauma situations. In these circumstances decisions are needed to assess how much fluid a patient needs and what type of fluid to give.

The Options

Intravenous fluids options may be classified into three categories: crystalloids, colloids, and blood products. Often patients are given both colloid and crystalloid. If fluid loss is undercorrected the patient will develop hypovolaemia, which may lead to renal impairment and other complications. Overcorrection can lead to pulmonary oedema and heart failure.

In seriously ill patients it is often best to insert a central venous pressure catheter while giving fluids. This allows the measurement of central venous (right atrial) pressure which can be used to assess if too much fluid is being given. This however, may not be possible in trauma (non-elective situations) such as road traffic accidents (RTAs) or on the battle field.

Crystalloid solutions

Crystalloids are substances that form a true solution and pass freely through a semi-permeable membrane. They contain water and electrolytes and stay in the intravascular compartment for a shorter time than colloids. Around two to three times more crystalloid than colloid is therefore needed to achieve an equivalent haemodynamic response. The expansion in intravascular volume achieved by a crystalloid solution is transitory; colloid osmotic pressure is reduced and as fluid accumulates in the interstitial spaces pulmonary oedema may occur. However, crystalloid solutions are convenient to use, and have no side effects.

Crystalloids are useful in maintaining fluid balance - for example, postoperatively when a patient is not drinking - or in conjunction with colloids to replace intravascular volume rapidly after sudden blood loss. The type of crystalloid given as fluid maintenance needs to be tailored to the need of the patient and has to take into account the daily requirement, insensible losses, and measured losses of fluid and electrolytes.

Normal saline (0.9% saline) is a commonly used saline solution. It contains water and 154 mmol/l of sodium and chloride ions. It is useful for maintaining the daily requirement of salt and water or for replacing gastrointestinal losses from nasogastric suction, vomiting, or enterocutaneous fistulae. Saline solutions can also be obtained with added potassium NaCl 0.9%, KCl 0.15% or glucose (dextrose-saline).

Normal saline is usually inappropriate in the early postoperative period because of the salt and water retention caused by the metabolic response to stress. However, if there is salt loss - for example, from the gastrointestinal tract - normal saline can be used to compensate this loss. Generally, replacement of the gastrointestinal volume lost with an equal volume of normal saline is sufficient. However, there may also be a need to account for potassium loss and compensate for it.

Dextrose solutions

The most commonly used dextrose solution is 5% dextrose, which contains water and 837 kJ/l energy in the form of glucose. Dextrose or dextrose-saline (which also provides 30 mmol/l of sodium chloride) are ideal to use in the early postoperative period since they do not cause salt and water overload and also provide some energy for the patient (albeit about 10% of the average daily requirement per litre). Care is needed to ensure that this is alternated with solutions that contain enough sodium.

Hartmann's solution (sodium lactate)

Sodium lactate solution has the advantage of containing less chloride and contains 29 mmol/litre of bicarbonate ions, which are present in solution as lactate and later converted in the liver to bicarbonate. It also contains 5 mmol/l of potassium and so has an electrolyte profile similar to plasma. Some clinicians prefer to use this solution in place of normal saline (0.9% saline), claiming that it is more physiological.

Colloids

Colloids are substances that do not dissolve into a true solution and do not pass through a semi-permeable membrane. Colloid solutions tend to stay in the intravascular compartment for longer than crystalloids, and therefore less volume is needed.

Colloids also increase colloidal osmotic (or oncotic) pressure, draining water out of the interstitial spaces into the intravascular compartment. However, when capillary permeability is increased colloids may leak across the capillary membrane and increase interstitial oncotic pressure, causing oedema. This may also happen if too much colloid is given. The highest risk is in the lungs where pulmonary oedema can interfere with gas exchange.

Colloid solutions are most useful in situations where the intravascular compartment needs to be expanded rapidly - for example, in severe hypovolaemia after major trauma. It is useful in a patient with severe haemorrhage before blood is available.

Colloids can be classified into natural colloids (this will be covered under blood products), dextrans, gelatines, and hydroxyethyl starches.

Dextrans

Dextrans are polysaccharides in solution with either normal saline or 5% dextrose. Types available include: dextran 40, in which the polysaccharides have an average molecular weight of 40000, and dextran 70, in which the average molecular weight is 70000. Both solutions are hypertonic and exert a powerful osmotic effect, drawing water from the extravascular compartment into the intravascular compartment. Dextran 40 is rapidly excreted by the kidney and therefore has a shorter half life than dextran 70. Both may interfere with cross matching of blood, it is therefore prudent to take blood samples before infusing dextrans. If dextrans have already been infused the haematology department should be informed so that the red blood cells can be washed prior to cross matching.

Gelatine

The gelatines commonly used are Haemaccel and Gelofusine and have a molecular weight of 35000 and 30000 respectively. They are isotonic, but because they are readily excreted by the kidney their half life in the circulation is only two to three hours.

Hydoxyethyl starches (hetastarch)

The hetastarches most commonly available are Elohes 6% and Hespan and have a molecular weight of 200000 and 450000 respectively. They are more expensive than dextrans and gelatines but cheaper than blood products. They expand the intravascular compartment slightly in excess of the volume infused and have a half-life of about six hours. They may improve the haemodynamic status for 24 hours or longer.

Blood products

There are risks associated with the use of blood products. These include infection with HIV, hepatitis B virus and hepatitis C virus. Other risks include allergic reactions, ABO incompatibility resulting in intravascular haemolysis of recipient red cells, fluid overload, antibody formation to donor granulocytes leading to leucocyte aggregation, and acute lung injury.

Blood

Transfusion with whole blood is required when the patient has a major bleed or is acutely anaemic - for example, after an operation where there has been significant blood loss. In emergency cases transfusion with uncrossmatched blood (group O, Rhesus negative) may be needed to save a patient's life, but it is usually possible to maintain the intravascular volume with plasma expanders until crossmatched blood is available.

Packed cells are concentrated suspensions of red cells prepared by removing most of the supernatant plasma citrate from the blood after settling of the blood or centrifugation. It is preferable to give packed cells if the patient is at risk of heart failure - for example, an elderly anaemic patient. In non-emergency situations a diuretic is commonly administered with the blood to avoid fluid overload (e.g. 20 mg oral frusemide with every other unit of blood). As a guide in an average person one unit of blood will raise the haemoglobin concentration by roughly 1g.

Plasma protein fraction (human albumin solution)

Human albumin solution is a good plasma expander. It has a half life of 5-15 days and may be used for plasma replacement in severely burnt patients.

Fresh frozen plasma

Fresh frozen plasma is usually given to patients with multiple coagulation defects associated with severe liver disease, intravascular coagulation, and massive blood transfusion. It has no place as a plasma expander. Patients with coagulation defects usually require four to six units over one to two hours. The transfusion should be repeated if the prothrombin time remains deranged.

Concentrates of specific factors

Concentrates prepared from plasma are available for factor VIII deficiency (haemophilia). Concentrates for other factor deficiencies such as antithrombin III and commercially made protein C are currently being assessed for clinical use.

Treatment of Hypovolaemia

Acute hypovolaemia due to blood loss

In patients who are hypovolaemic and losing blood it is important to stem any external bleeding using pressure, set up a good peripheral intravenous line using a large cannula, take blood for cross matching and baseline haemoglobin concentration, and start rapid infusion of 500 ml of normal saline followed by a colloid solution. If the bleeding is catastrophic unmatched O negative blood (universal donor blood) should be requested. An estimate of the volume of blood lost should be made and the amount requested as whole blood (it is better to err on the side of caution and overestimate the blood loss). If the bleeding is persistent once the patient is stable (systolic blood pressure over 100 mm Hg) a central venous pressure line is frequently inserted and a urinary catheter to monitor progress. Whole blood in appropriate quantities is normally given as soon as it is available.

Gradual hypovolaemia

Gradual hypovolaemia usually arises in a patient whose fluid loss is persistent and its full extent not appreciated. The usual signs of this are tachycardia and reduced urine output. In severe cases hypotension may occur. In these cases a fluid challenge may be needed to determine if the reduced urine output is due to hypovolaemia. Give 200 ml of colloid rapidly (a central venous pressure line may be needed in patients with myocardial compromise). If this improves the urine output and blood pressure with only a transient or no improvement in the central venous pressure, then hypovolaemia is confirmed and further fluids are given as appropriate.

RescueFlow^® - a new treatment concept

RescueFlow^® is a 250 ml solution containing 7.5% sodium chloride and 6% dextran 70. It introduces the concept of ‘Small Volume Resuscitation’. This consists of combining the rapid plasma volume effect of hypertonic saline with a colloid's water-binding properties. The hypertonic properties create an osmotic gradient that allows fluid to move from the extravascular to the intravascular space.

The increase in intravascular volume provided by 250 ml of RescueFlow has been found to be two to three times the infused volume, similar to the increase in volume resulting from intravenous administration of three litres of crystalloid solution. Treatment benefits have been observed for patients with severe injuries (trauma) such as penetrating injury requiring surgery and for patients requiring intensive care.

RescueFlow^®

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