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IV fluid management: hypovolaemia and volume replacement fluids


Hypovolaemia causes poor tissue perfusion, which in turn leads to organ dysfunction and adverse clinical outcomes. The correction of hypovolaemia most often requires intravenous fluid therapy, and there are a variety of fluids which exist for this purpose

V Nagaratnam
Specialty Registrar
Anaesthesia, UCL
Hospital, London, UK
E Burdett
Clinical fellow –
Anaesthesia, UCL
Hospital, London, UK
M Mythen
Smiths Medical
Professor of Anaesthesia
and Critical Care, UCL
Director, Joint UCLH/
UCL Biomedical
Research Unit
National Clinical Lead,
Enhanced Recovery
Partnership Programme,

Lack of effective circulating blood volume is termed hypovolaemia and is common in clinical practice. Whilst its aetiology is varied, its correction requires replacement of the losses. This could be done enterally, but in practise circumstances may not allow this. In these cases, correction is performed parenterally, using intravenous fluids.

These fluids are among the most commonly prescribed drugs in the hospital setting. Crystalloids consisting of a simple electrolyte solution are easily available and cost-effective, whilst colloid solutions containing a suspension of macromolecules are available, which stay in the circulation for longer. Some fluids such as 0.9% saline are simply isotonic, whilst others such as Hartmanns solution more closely maintain normal plasma electrolyte balance.

Hypovolaemia and its significance
Hypovolaemia describes an effective inadequacy in the volume of the intravascular circulating fluid resulting in poor tissue perfusion. It can be due to loss of fluid, for example whole blood (haemorrhage), loss of a combination of salt and water (capillary leak), or a loss of water, (dehydration).[1] Hypovolaemia can also occur in the presence of a normal circulating volume, when the body’s requirement for intravascular volume to splint the circulation is increased, for example in some disease states such as sepsis.[2]

Hypovolaemia results in reduced transport of nutrients to the tissues, which can cause organ failure. In clinical practice, hypovolaemia can be recognised by elevated pulse, diminished blood pressure, and the absence of perfusion as assessed by skin signs (skin turning pale) and/or reduced capillary refill on forehead, lips and nail beds. The subject may feel dizzy,
faint, nauseated, or thirsty.

Physiological rationale for fluid therapy
Hypovolaemia strains the ability of the body to adequately perfuse the tissues. An inadequate venous return to the heart soon results in suboptimal cardiac stroke volume. This leads to activation of compensatory measures such as tachycardia and peripheral vasoconstriction as the body struggles to maintain perfusion to the central organs.

Distribution of fluid across capillary membranes in the body is influenced by Starling forces. (See diagram 1). The balance between the hydrostatic and osmotic pressures generate movement of water and dissolved solutes to and from the tissues. A correct balance of these forces and maintenance of the integrity of the capillary membrane is required to ensure that the tissues are both adequately perfused and adequately drained.

An inadequate hydrostatic pressure due to hypotension caused by hypovolaemia will result in inadequate tissue perfusion, and net movement of fluid from the tissues to the intravascular space to correct the imbalance.

Some disease processes such as sepsis and anaphylaxis can cause increased capillary permeability which in turn leads to leak. This leads to a net loss of fluid from the intravascular space, and a consequent relative hypovolaemia. Moreover, any fluid that is used in the resusciative process has the potential to leak out into the interstitial space. (See table 1)

The ideal intravenous fluid
In order to correct hypovolaemia, the ideal intravenous replacement fluid would have to maintain cardiac output and restore the balance between the hydrostatic and osmotic pressures, and thereby optimise tissue perfusion without resulting in fluid overload or tissue oedema. Some other properties of the ideal intravenous fluid are listed in Table 2.

Crystalloids in clinical usage
These are solutions of electrolytes in water. When an iso-osmotic crystalloid is infused, such as Hartmanns solution, it is distributed throughout the extracellular fluid (ECF), and therefore only one third effectively remains in the intravascular space. However, if a hypoosmolar fluid is infused, such as 5% dextrose, it is distributed throughout the total body water, and as such less than 10% of the original volume remains in the intravascular space.[3]

Saline 0.9% is a commonly used intravenous fluidand consists of sodium chloride dissolved in water. (See table 3). With an osmolarity of 308 mmol l-1, it is roughly isotonic and iso-osmotic with plasma but contains a great deal more chloride than normal extracellular fluid (ECF). As a result, administration of large volumes of normal saline cause hyperchloraemia, resulting in metabolic acidosis, which may have adverse effects on several organ systems.


Hartmann’s solution is more close in its formulation to the compositon of normal plasma. (See table 3). It contains lactate which is metabolised mainly by gluconeogenesis in the liver; a relative excess of bicarbonate ions is produced reducing acidosis in a controlled fashion. Moreover it has less chloride than saline, reducing the chances of hyperchloraemic metabolic acidosis.[4]

Dextrose 5% is not suitable for the treatment of hypovolaemia, because although at first glance it is isoosmotic weith plasma, the dextrose is rapidly metabolised and the fluid therefore functions as free water.This fluid effectvely has an osmotic pressure of 0. The net effect is that the total volume of fluid is distributed to all fluid compartments in proportion to their contribution to total body water.

Colloids in clinical usage
A colloid is a fluid which suspends larger molecules in an iso-osmotic crystalloid solution. These molecules do not cross the capillary membrane so much, exerting a colloid oncotic pressure, and encouraging fluid to remain within the intravascular space. Therefore, compared to the use of crystalloids to treat hypovolaemia, less volume is required and there is less risk of peripheral or pulmonary oedema. However, increased amounts of colloid may leak into the interstitial fluid and paradoxically increase the interstitial oncotic pressure, thus exacerbating oedema if vascular permeability is increased. Colloids have other effects: there is a risk of allergic reactions, and some have adverse effects on specific organs such as the kidney or the coagulation system. There is an increased cost in comparison to crystalloids.

Gelatins are the most commonly used type of colloid solution in Europe for volume replacement. They are polypeptide-based degradation products of animal collagen. Their time in the intravascular compartment may be longer than that of crystalloids, at 1–4 hours; and the risk of histamine reactions associated with gelatins is relatively high.

Hydroxyethyl starches are more used extensively in the USA, and composed of amylopectin that is linked with hydroxyethyl groups to make a glycogen-like polymer. They are suspended in a crystalloid solution, either saline based or balanced, and have a large range of molecular weights (MW). They stay in the intravascular space for at least 4 hours, and have a lower risk of anaphylaxis. High molecular weight straches are linked with adverse effects on renal function and coagulation; more modern starches have a lower MW and a lower degree of substitution which may reduce in these effects. There is a potential problem with long-term pruritis with the use of hydroxyethyl starch.


Dextrans are branched chain polysaccharides and available as 6–10% solutions in normal saline. Their use in the teatment of hypovolaemia has been limited by their relatively high risk of anaphylaxis, and the increased risk of bleeding due to their interaction with platelets. There may be a role for them in improving microvascular flow during free flap surgery.

Human albumin solution (HAS) is derived from pooled human plasma by fractionation. It is heat sterilised rendering the risk of infective transmission very low. It is seldom used for the treatment of hypovolaemia. A number of clinical trials showing no benefit, or even potential worsening of outcome when compared to other intravenous fluids for volume replacement has led to a diminished use. It is expensive in many countries.

Dosage and monitoring
Intravenous fluids should be used with care to achieve adequate correction of hypovolaemia without fluid overload. A dynamic approach is preferred, measuring response to repeated small boluses (the ‘fluid challenge’).[5] For the treatment of mild hypovolaemia, progress may be monitored clinically, measuring vital signs. However for the seriously ill, or those with major comorbidities, more invasive methods may be considered, which rely on measurement of filling pressures or cardiac output (See diagram 2). The response to a fluid challenge is measured, and from this an assessment of volume status is made: for example, the patient is considered to be fluid responsive if the left ventricular stroke volume rises in response to a 250 ml intravenous fluid challenge; or the central venous pressure rises by less than 3 mmHg.

Risks of fluid therapy
Intravenous fluid therapy is not physiological, and its use should be avoided where alternatives exist. Apart from the specific risks mentioned above, all intravenous fluid therapy has the potential to cause infection, phlebitis, fluid overload, electrolyte imbalances, air embolism and extravasation

It is important to correct hypovolaemia in order to maintain perfusion of vital organs. Whilst there is no ideal fluid, there are a number of strategies which may be used to treat it; the exact one depends upon the individual patient. In any case, intravenous fluid therapy should be carefully monitored and stopped as soon as appropriate.

1. Guyton AC , Hall JE. The body fluid compartments. In: Textbook of Medical Physiology. 11th ed. Elsevier 2006.
2. Parsons PE, Wiener-Kronish JP. Fluid Management In: Critical Care Secrets 4th ed. Mosby 2007.
3. Floss K, Moswela O. Basic fluid physiology and principles of fluid therapy. HPE 45 July/August 2009.
4. Burdett E, Roche AR, Mythen MG. Hyperchloremic acidosis: pathophysiology and clinical impact. Transfusion alternatives in transfusion medicine. 2008 5:4;424–30
5. Al-Khafaji M, Webb A. Fluid resuscitation. Continuing Education in Anaesthesia, Critical Care & Pain 2004;4:127–131

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