The fluid challenge - when and how much?

The mainstay of resuscitation and ongoing ICU care is fluid management. Despite its importance and the huge amount of literature on the subject the question of ‘when and how much’ has no universally accepted answer.

The ultimate goal of resuscitation with fluids, vasopressors and inotropes is to ensure adequate oxygen delivery (DO2) to prevent or treat organ dysfunction. There are some fundamental principles which must be held in mind:

Fundamental principles

DO2 = CaO2 x CO
(note this is for global DO2, individual organ perfusion is also pressure dependent ie MAP)

CO = SV x HR


SV is dependent on preload (end diastolic wall tension), contractility and afterload (end systolic wall tension).

Preload is determined by venous return which is in turn determined by the pressure gradient between the veins and the R atrium. The pressure in the veins is termed 'mean circulatory filling pressure' or 'mean systemic pressure' by different authors. This is described as the average pressure within the veins or the pressure that would be present in the vasculature if cardiac output ceased. The opposing pressure to VR is the RAP. VR is also inversely proportional to the resistance of the veins. Thus:

VR = MCFP - CVP / venous resistance

MCFP is regulated by the sympathetic nervous system’s effect on the splancnic venous system. The splancnic venous system contains 20% of total blood volume, is 30 times more compliant than the arterial circulation and is heavily innervated with ɑ receptors. It is essentially a reservoir of blood made up of capacitance vessels easily able to change in volume to maintain venous return to the heart. A useful analogy is a tank of water with an outlet 1/2 way up the tank. The fluid below the outlet is unstressed venous volume (not contributing to flow out of the tank) and the fluid above is stressed volume. The height of the liquid is equivalent to MCFP. The height of the outlet is proportional to CVP (or RAP). Lowering RAP (if nothing else changed) would increase VR. Stressed volume can be increased by giving fluid (as long as the size of the tank does not increase from reflex venodilatation) or reducing the size of the tank (giving a venopressor to convert unstressed to stressed volume). Either of these will increase the pressure gradient between MCFP and CVP and increase venous return. Fluid will also dilate the veins and reduce venous resistance. If both ventricles are preload dependent (on the steep part of the starling curve), SV will increase.


Knowing how to optimise DO2 in a patient with MOF is not straightforward especially when they have already received fluids and are on vasopressors and/or inotropes. Fluid optimisation is the 1st step - vasopressors in hypovolaemia will reduce SV via increased afterload while inotropes would cause myocardial stress via O2 demand exceeding supply with a possible resultant fall in SV. It is important to remember however that vasodilation in SIRS predominantly affects the splancnic venous circulation (which, as above, is 30 times more compliant than the arterial circulation). Vasopressors in this case will increase preload by contracting the splancnic veins and thus increase cardiac output (with no or minimal afterload increase, or even a reduction because of the increased CO -
noradrenaline has been shown to reduce afterload). It may be more appropriate and effective (as in neuraxially blocked patients in anaesthesia) to give vasopressors rather than, or along with, fluid in these circumstances. To counter this, noradrenaline has been shown to unmask or even promote LV systolic dysfunction in up to 30% of cases of septic shock by increasing afterload (patients who had underlying systolic dysfunction whose function initially appeared ok due to reduced afterload). The answer to this is to measure SV to see what effects are produced.
Giving fluid, when needed, to increase SV is clearly vitally important. Unnecessary fluid administration however causes harm via increased organ dysfunction (secondary to oedema) with prolonged weaning, length of stay, worse oxygenation index and trends towards increased mortality and requirement for RRT (ARDSnet). Despite its importance, unfortunately knowing when to five fluid and how much to give causes much confusion. Fluid loading fails to increase CO in about 50% of ICU patients or in other words half of the fluid challenges we give are unnecessary and are therefore potentially harmful.


Clinical signs are neither sensitive or specific. Traditionally, static markers to predict fluid responsiveness such as CVP and PAWP and estimation (PAC, PICCO) and measurement (ECHO) of ventricular volumes have been used - indeed the surviving sepsis guidelines advocate the use of CVP to predict fluid responsiveness. But, as stated above, preload is end diastolic wall stress and not end diastolic pressure or end diastolic volume.
Ventricular wall stress can be estimated using Laplace’s law, modified for thick walled structures. This is expressed as Lamé's equation:

σ (P1 - P2) x R / w

σ = wall stress; P1 = intraventricular pressure; P2 = extraventricular pressure; R = ventricular radius; w = wall thickness.

This is clearly impractical to use in clinical practice and has no evidence base that I know of.
Added to this is the fact that the relationship between preload and stroke volume also depends on ventricular contractility which is often impaired in critically ill patients. Hence, even in theory, the static markers mentioned should have little correlation with stroke volume or fluid responsiveness. There is some evidence to suggest that very low values for CVP/PAOP and a very small ventricular hyper dynamic LV (on echo) is correlated with fluid responsiveness but for most values there is no correlation. This is born out by a huge amount of evidence which since the 1970’s has clearly and repeated demonstrated that static markers are of no use in predicting fluid responsiveness. A recent study by Osman et al. confirmed cardiac filling pressures (CVP and PAOP) are unable to predict fluid responsiveness. They had positive and negative predictive values of 54% and 63%. In other words you might as well use a coin toss as look at CVP or PAOP values.
More recently, a number of dynamic indices have been shown to predict fluid responsiveness. These include Systolic Pressure Variation (SPV), Pulse Pressure Variation (PPV), Stroke Volume Variation (SVV), preejection period and vena cava diameter variation (SVC and IVC). These require an explanation of heart-lung interactions.
It is important to remember they are rendered inaccurate by failure of either ventricle (afterload changes), arrhythmias (apart from VC diameter), spontaneous breathing and a tidal volume of <8mls/kg. Passive leg raising (PLR) overcomes these difficulties. It effectively provides a fluid challenge of around 300 mls to the central circulation which has the advantage of being completely reversible. It has been shown to be even more accurate than PPV having a sensitivity and specificity of over 90%.
PLR can be falsely negative in severe hypovolaemia (reduced blood volume in the legs).

One thing which is vital to bear in mind is that fluid responsiveness does not necessarily mean that fluid should be given. If a fit, healthy, normovolaemic person is ventilated with a large tidal volume, the dynamic indices above may well predict fluid responsiveness. If fluid is then given, urine output and SV will likely increase.

Fluid should only be given if there are signs of fluid responsiveness
and the presence of haemodynamic failure.

Critically ill patients are commonly given far too much fluid which causes organ oedema and dysfunction. As stated above fluid loading fails to increase cardiac output in 50% of ICU patients meaning that half of the time we get it wrong. This is unacceptably poor practice and we should perform much better.

How much?

This is more difficult to answer. One proposed method is to use the dynamic change in CVP to guide the volume given. The theory of this approach is that the right ventricle is very compliant and is able to adapt its stroke volume to a large range of venous return without affecting the value of the CVP. There will come a point however where the right ventricle will no longer be able to adapt and CVP will rise. It has been proposed that this phenomenon can be used to guide volume replacement with a sustained rise in the CVP by 3 equating to the upper flat portion of the starling curve. Unfortunately, a study by Kumar et al showed there was no correlation between changes in CVP or PAOP (in response to fluid loading) and variations in cardiac performance indices.

Much more appropriate is to either:

Give fluid until the dynamic indices above no longer predict fluid responsiveness.

Give fixed volume boluses until there is no significant increase (>10%) in measured SV.
SV is more appropriate to use than CO as CO is influenced by heart rate which may compensate for changes in SV.

Changes in pulmonary hydrostatic pressure are determined by the LV pressure volume curve. Severely hypovolaemic patients will have an increase in LVEDV much more than LVEDP with fluid administration. With lesser degrees of hypovolaemia, even 'fluid responsive' patients on the steep part of the starling curve may increase their LVEDP significantly depending on their LV contractility and compliance.
Estimating PAOP pressure (easy with echo) by MV doppler indices before and after a fluid challenge can help guide when to stop.
A positive response to a fluid challenge would be an increase in SV of >10%.
A negative response would be an increase in PAOP with an increase of SV of <10%.
Note here how an increase in PAOP is used to
stop a fluid challenge rather than looking for an increase as a positive response.

Assessment of fluid responsiveness and monitoring of response with echocardiography.

Which Fluid?
The only resuscitation fluid you should use is Compound Sodium Lactate (Hartmanns). There are exceptional circumstances when 1.26% sodium bicarb is appropriate (hyponatraemic acidosis).
See crystalloids vs colloids


Giving fluids is often regarded as an art rather than a science. It is true that many factors need to be considered when deciding when and how much fluid to give, but there is much evidence available to make your decision scientific. These lessons can be summarised as some fundamental questions I consider when deciding to give fluid:

Is CO and MAP adequate for organ perfusion? - measurement of MAP, CO, SVO2,
lactate, clinical examination.
Is the patient likely to be fluid responsive? - don’t use static indices; use the dynamic indices above.
How much should I give? - give fluid until dynamic indices show not likely to be fluid responsive or SV no longer increases.
Then stop - more fluid will cause harm.
Which fluid? - Compound Sodium Lactate (Hartmanns) is the only resuscitation fluid you should use (see crystalloids vs colloids). This should only be given in boluses - it is not a maintenance fluid and to use it as one is lazy and may harm your patients (see hypernatraemia).

Crucially, all of these require clinician presence at the bedside until optimisation has occurred.


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Osman D, Ridel C, Ray P et al. Cardiac filling pressures are not appropriate to predict haemodynamic response to volume challenge, Crit Care Med. 2007;35(1):64-8.

Monnet X, Rienzo M, Osman Det al. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med. 2006;34:1402-7

The National Heart, Lung, and Blood Institute Acute Respiratory Distress
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