Fluids
Last updated 27th April 2020 - Tom Heaton
Fluids can be categorised as:
The physiology of fluids in the body is important to understand and is discussed elsewhere.
- Crystalloids
- Colloids
The physiology of fluids in the body is important to understand and is discussed elsewhere.
Crystalloids
Crystalloids are a solution of different electrolytes and small molecules.
These can pass freely through semipermeable membranes, although the different membranes in the body have important restrictions (which is important).
They can be more generally split into:
The ‘extracellular fluid replacement’ has an electrolyte composition (primarily sodium) that is close to that of extracellular fluid.
This keeps an electrochemical ‘draw’ on the administered fluid, keeping it extracellular in location.
Examples include:
Total body water replacement fluids do not have such an electrolyte composition.
This means that after administration, there is not the electrochemical drag to keep the water in the extracellular space.
This allows the water to move freely, distributing itself evenly across the body compartments.
Examples include:
Additional special solutions include:
These can pass freely through semipermeable membranes, although the different membranes in the body have important restrictions (which is important).
They can be more generally split into:
- Extracellular fluid replacement
- Total body water replacement
- Special solutions
The ‘extracellular fluid replacement’ has an electrolyte composition (primarily sodium) that is close to that of extracellular fluid.
This keeps an electrochemical ‘draw’ on the administered fluid, keeping it extracellular in location.
Examples include:
- Plasmalyte
- Hartmann’s solution
- Normal saline
Total body water replacement fluids do not have such an electrolyte composition.
This means that after administration, there is not the electrochemical drag to keep the water in the extracellular space.
This allows the water to move freely, distributing itself evenly across the body compartments.
Examples include:
- 5% Glucose
Additional special solutions include:
- Sodium bicarbonate
- Mannitol
- Alternative concentration saline (hyper or hypotonic)
- Higher concentration glucose
Normal Saline
Sodium chloride at a concentration of 0.9%.
Na+ = 154mmol/L
Cl- = 154mmol/L
Osm = 300 mOsm/L
pH = 5-6.5
Whilst described as ‘normal’ saline, it really is quite an abnormal solution compared to physiological fluids.
Whilst the osmolality is about right (and this is one of the most important features of fluids to allow administration IV), there is an excess of both sodium and chloride compared to plasma, with an absence of other key components e.g. potassium.
Advantages:
Disadvantages:
SPLIT trial - https://www.thebottomline.org.uk/summaries/icm/split/
RCT comparing Plasmalyte with 0.9% NaCl as IV fluid.
No difference in rates of AKI or mortality.
Only relatively small volumes of fluid given though and a signal towards worse outcome with NaCl 0.9%.
SALT-EM - https://www.thebottomline.org.uk/summaries/icm/salt-em/
Large RCT comparing balanced crystalloid with 0.9% as fluid for general admissions.
Increased risk of major adverse kidney events at 30 days (MAKE 30 - secondary outcome) in 0.9% NaCl group.
SMART - https://www.thebottomline.org.uk/summaries/icm/smart/
Similar to SALT-EM, but looking at ICU level patients.
Increased risk of MAKE 30 adverse outcome in saline group.
Suggestion of worse outcome in sicker sepsis subgroup (hypothesis generating only).
Supported previous suggestion that saline has an increased risk of adverse renal outcomes.
Some guidelines now suggest avoiding NaCl 0.9% unless specifically indicated:
Na+ = 154mmol/L
Cl- = 154mmol/L
Osm = 300 mOsm/L
pH = 5-6.5
Whilst described as ‘normal’ saline, it really is quite an abnormal solution compared to physiological fluids.
Whilst the osmolality is about right (and this is one of the most important features of fluids to allow administration IV), there is an excess of both sodium and chloride compared to plasma, with an absence of other key components e.g. potassium.
Advantages:
- Commonly available with higher concentration potassium
- May be the desired balance of electrolytes in some clinical scenarios e.g. hyponatraemia, hypochloraemia.
Disadvantages:
- High chloride load can lead to hyperchloraemic metabolic acidosis
- Needs additional K+ if used as maintenance
- Suggestion of risk of renal injury with use
SPLIT trial - https://www.thebottomline.org.uk/summaries/icm/split/
RCT comparing Plasmalyte with 0.9% NaCl as IV fluid.
No difference in rates of AKI or mortality.
Only relatively small volumes of fluid given though and a signal towards worse outcome with NaCl 0.9%.
SALT-EM - https://www.thebottomline.org.uk/summaries/icm/salt-em/
Large RCT comparing balanced crystalloid with 0.9% as fluid for general admissions.
Increased risk of major adverse kidney events at 30 days (MAKE 30 - secondary outcome) in 0.9% NaCl group.
SMART - https://www.thebottomline.org.uk/summaries/icm/smart/
Similar to SALT-EM, but looking at ICU level patients.
Increased risk of MAKE 30 adverse outcome in saline group.
Suggestion of worse outcome in sicker sepsis subgroup (hypothesis generating only).
Supported previous suggestion that saline has an increased risk of adverse renal outcomes.
Some guidelines now suggest avoiding NaCl 0.9% unless specifically indicated:
- BAPEN
Hartmann's Solution
A more balanced crystalloid.
Na+ 131mmol/L
Cl- = 111mmol/L
K+ = 5mmol/L
Ca2+ = 2mmol/L
HCO3- = 29mmol/L (as lactate)
Osm = 278mOsm/L
pH = 6.5
Advantages:
Disadvantages:
Na+ 131mmol/L
Cl- = 111mmol/L
K+ = 5mmol/L
Ca2+ = 2mmol/L
HCO3- = 29mmol/L (as lactate)
Osm = 278mOsm/L
pH = 6.5
Advantages:
- More balanced composition with less physiological disturbance
Disadvantages:
- Inadequate K+ for daily needs - this would require addition of K+ which is a recognised higher risk intervention.
Glucose 5%
Contains 50g of glucose per litre.
Around 205 calories.
Can be considered as pure water from a body fluid perspective, as glucose is rapidly taken up by cells, allowing diffusion of the water through all the fluid compartments.
Advantages
Disadvantages
Around 205 calories.
Can be considered as pure water from a body fluid perspective, as glucose is rapidly taken up by cells, allowing diffusion of the water through all the fluid compartments.
Advantages
- Provides water without electrolytes, which may be indicated in some clinical scenarios e.g. hypernatraemia
- Can be a source of calories
Disadvantages
- Lack of electrolytes can lead to notable electrolyte disturbances
Colloids
These contain large molecules dispersed evenly throughout the solution.
These molecules are unable to pass through cell membranes, and are generally too large to leave the intravascular space (at least initially).
As such they will tend to remain in the intravascular space, exerting an osmotic effect and keeping the fluid in this space.
They are commonly categorised into natural and synthetic.
Examples include:
Natural
These molecules are unable to pass through cell membranes, and are generally too large to leave the intravascular space (at least initially).
As such they will tend to remain in the intravascular space, exerting an osmotic effect and keeping the fluid in this space.
They are commonly categorised into natural and synthetic.
Examples include:
Natural
- Albumin
- Blood
- Dextrans
- Gelatins
- Starches
Albumin
This is a naturally occurring colloid, made from heat-treated human albumin.
It usually comes in 4-5% or 20% concentrations, in a crystalloid solution.
It is produced at a low pH but not technically sterile, thus needing to be used within 3 hours of opening.
As well as providing colloid oncotic pressure, it can also affect drug binding.
It is a highly negatively charged molecule, being repelled by the negative charge of the glycocalyx, and can result in an intravascular duration of 5-10 days (when the capillary endothelium is intact).
In health it has a number of important functions:
In keeping with this physiology it appears to have a better impact on improving CVS parameters, although the evidence of translation into improved outcomes isn’t really there.
It appears to worsen outcome in brain injury, possibly due to translocation into the brain tissue (because of a damaged blood brain barrier) where the oncotic effect is detrimental.
The key studies:
ALBIOS - https://www.thebottomline.org.uk/summaries/icm/albios-study-investigators-albumin-replacement-in-patients-with-severe-sepsis-or-septic-shock/
RCT assessing the use of 20% HAS in severe sepsis - using 300ml 20%/24h to keep albumin levels > 30g/l.
Other fluid treatment was not altered, and quite high (median 3,738ml/24h in first 7 days).
No difference in mortality (31.8% vs 32%).
Did improve CVS indices and suggestion of improved mortality in the septic shock subgroup analysis (43.6% vs 49.9%, ot statistically significant).
SAFE - https://www.thebottomline.org.uk/summaries/icm/safe/
RCT comparing 4% HAS with 0.9% NaCl for resuscitation in a wide variety of ICU patients.
No significant difference in 28 day mortality (20.9% vs 21.1%, p=0.87).
Significant increase in mortality in patients with brain injury (24.5% vs 15.1%, p=0.009, post hoc analysis).
Other indications for HAS include:
It usually comes in 4-5% or 20% concentrations, in a crystalloid solution.
It is produced at a low pH but not technically sterile, thus needing to be used within 3 hours of opening.
As well as providing colloid oncotic pressure, it can also affect drug binding.
It is a highly negatively charged molecule, being repelled by the negative charge of the glycocalyx, and can result in an intravascular duration of 5-10 days (when the capillary endothelium is intact).
In health it has a number of important functions:
- Maintaining oncotic pressure
- Transport molecule
- Hormones
- Unconjugated bilirubin
- Acidic drugs
- cations
- Hormones
- Buffer function
In keeping with this physiology it appears to have a better impact on improving CVS parameters, although the evidence of translation into improved outcomes isn’t really there.
It appears to worsen outcome in brain injury, possibly due to translocation into the brain tissue (because of a damaged blood brain barrier) where the oncotic effect is detrimental.
The key studies:
ALBIOS - https://www.thebottomline.org.uk/summaries/icm/albios-study-investigators-albumin-replacement-in-patients-with-severe-sepsis-or-septic-shock/
RCT assessing the use of 20% HAS in severe sepsis - using 300ml 20%/24h to keep albumin levels > 30g/l.
Other fluid treatment was not altered, and quite high (median 3,738ml/24h in first 7 days).
No difference in mortality (31.8% vs 32%).
Did improve CVS indices and suggestion of improved mortality in the septic shock subgroup analysis (43.6% vs 49.9%, ot statistically significant).
SAFE - https://www.thebottomline.org.uk/summaries/icm/safe/
RCT comparing 4% HAS with 0.9% NaCl for resuscitation in a wide variety of ICU patients.
No significant difference in 28 day mortality (20.9% vs 21.1%, p=0.87).
Significant increase in mortality in patients with brain injury (24.5% vs 15.1%, p=0.009, post hoc analysis).
Other indications for HAS include:
- Prophylaxis/management of hepatorenal syndrome
- To ‘cover’ for ascitic drainage
- As a fluid replacement during plasmapheresis
Gelatins
These are high molecular weight proteins produced by collagen hydrolysis.
They are probably the only synthetic colloid still used (for now).
They have a risk of anaphylaxis associated with them but do not interfere with clotting.
An advantage is their long shelf life.
They are relatively smaller molecules (35 kDa) and so fairly rapidly excreted by the kidneys (plasma half life around 2.5 hours).
Advantages:
Disadvantages:
They are probably the only synthetic colloid still used (for now).
They have a risk of anaphylaxis associated with them but do not interfere with clotting.
An advantage is their long shelf life.
They are relatively smaller molecules (35 kDa) and so fairly rapidly excreted by the kidneys (plasma half life around 2.5 hours).
Advantages:
- Easy storage - Long shelf life, no refridgeration
- Reduced infection risk compared to natural colloids
- Lower volume of infusion compared to crystalloids
Disadvantages:
- Anaphylaxis risk
- Higher cost compared to crystalloids
- No evidence of benefit compared to crystalloids
Dextrans
E.g. Macrodex
As the name suggests, these are high molecular weight sugars (40-70 Da), produced from sucrose by bacteria.
It has a duration of action of 6-8 hours.
Disadvantages
As the name suggests, these are high molecular weight sugars (40-70 Da), produced from sucrose by bacteria.
It has a duration of action of 6-8 hours.
Disadvantages
- Anaphylaxis risk
- Interfere with haemostatic pathways (due to VWBF interference)
- Interfere with blood cross matching.
Starches
The hydroxyl-ethyl starches (HESs) are no longer really used due to their adverse effects.
They have a risk of anaphylaxis, cause kidney injury and accumulate in the reticuloendothelial system.
The key studies:
CHEST - https://www.thebottomline.org.uk/summaries/icm/chest/
RCT by ANZICS group comparing HES with normal saline fluid resuscitation in critically ill patients requiring fluid therapy.
Double blinded with 7000 patients recruited.
Critically ill patients with a few groups excluded - burns, ICH, cardiac surgery
No difference in primary end point of all cause 90 day mortality (18% vs 17%, p 0.26).
Increased use of RRT in HES group (7.0 vs 5.8%, p 0.04).
6S - https://www.thebottomline.org.uk/summaries/icm/6s/
RCT comparing HES with Ringer’s acetate fluid resuscitation in patients with severe sepsis.
Double blinded with 804 patients recruited.
Significant increase in death or RRT dependence at 90 days with HES (51% vs 43%, p 0.03).
Increased use of RRT in HES group (22% vs 16%, p 0.04).
CRISTAL - https://jamanetwork.com/journals/jama/fullarticle/1752245
RCT comparing crystalloid vs colloid for fluid in hypovolaemic ICU patients.
Of note, mostly used starches (69%) with gelatins for 35%, albumin 4% in 6% and albumin 20% in 14%.
No difference in 28 mortality but improved 90 mortality in colloid group.
Also small improvements in time on a ventilator and vasopressor time.
It seems interesting given the conflicting results from the specific trials with starches and thus what the effects would look like if these weren’t used.
They have a risk of anaphylaxis, cause kidney injury and accumulate in the reticuloendothelial system.
The key studies:
CHEST - https://www.thebottomline.org.uk/summaries/icm/chest/
RCT by ANZICS group comparing HES with normal saline fluid resuscitation in critically ill patients requiring fluid therapy.
Double blinded with 7000 patients recruited.
Critically ill patients with a few groups excluded - burns, ICH, cardiac surgery
No difference in primary end point of all cause 90 day mortality (18% vs 17%, p 0.26).
Increased use of RRT in HES group (7.0 vs 5.8%, p 0.04).
6S - https://www.thebottomline.org.uk/summaries/icm/6s/
RCT comparing HES with Ringer’s acetate fluid resuscitation in patients with severe sepsis.
Double blinded with 804 patients recruited.
Significant increase in death or RRT dependence at 90 days with HES (51% vs 43%, p 0.03).
Increased use of RRT in HES group (22% vs 16%, p 0.04).
CRISTAL - https://jamanetwork.com/journals/jama/fullarticle/1752245
RCT comparing crystalloid vs colloid for fluid in hypovolaemic ICU patients.
Of note, mostly used starches (69%) with gelatins for 35%, albumin 4% in 6% and albumin 20% in 14%.
No difference in 28 mortality but improved 90 mortality in colloid group.
Also small improvements in time on a ventilator and vasopressor time.
It seems interesting given the conflicting results from the specific trials with starches and thus what the effects would look like if these weren’t used.
Links & References
- LITFL. Part one. Intravenous fluids. http://www.partone.lifeinthefastlane.com/intravenous-fluids.html
- Hill, S. Intravenous fluids. e-LFH. 2016. https://portal.e-lfh.org.uk/Component/Details/433187
- British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients (GIFTASUP). 2018. https://www.bapen.org.uk/resources-and-education/education-and-guidance/bapen-principles-of-good-nutritional-practice/giftasup
- Myburgh, J. et al. CHEST Trial. NEJM. 2012. 367: 1901-1911. https://www.nejm.org/doi/full/10.1056/NEJMoa1209759#t=article
- ALBIOS. https://www.nejm.org/doi/full/10.1056/NEJMoa1305727#t=article
- Flavin, K. et al. Questions for the final FFICM structured oral examination. 2018. Cambridge University Press.
- Fluid Book. AnaesthesiaMCQ.com. http://www.anaesthesiamcq.com/FluidBook/fl7_3.php
- Wong, A. SPLIT. The Bottom Line. 2015. https://www.thebottomline.org.uk/summaries/icm/split/
- Magee, F. SALT-EM. The Bottom Line. 2018. https://www.thebottomline.org.uk/summaries/icm/salt-em/
- Bradford, C. SMART. The Bottom Line. 2018. https://www.thebottomline.org.uk/summaries/icm/smart/
- Chambler, D. ALBIOS. The Bottom Line. 2014. https://www.thebottomline.org.uk/summaries/icm/albios-study-investigators-albumin-replacement-in-patients-with-severe-sepsis-or-septic-shock/
- Slessor, D. SAFE Study. The Bottom Line. 2014. https://www.thebottomline.org.uk/summaries/icm/safe/
- Chambler, D. CHEST. The Bottom Line. 2015. https://www.thebottomline.org.uk/summaries/icm/chest/
