• Third space

• Fluid deficit
• Balanced salt solutions
• Colloids

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 Time out

Think about your body

weight...

...what percentage of this

do you think is made up of
water?

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3
Time out

40–60% of adult body

weight is made up of
water (fluid)1

Mullins RJ. Shock, electrolytes, and fluid. In: Townsend CM, et al. (eds). Townsend: Sabiston Textbook of Surgery. 18th ed. Philadelphia, PA: Elsevier Saunders; 2007.

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4
How the body's fluid is distributed
Body fluids exist in two major ‘compartments’

Cell
1. Intracellular fluid (ICF)
= Inside the cells
Intracellular Blood
2. Extracellular fluid (ECF) fluid (in capillaries)
Outside the cells
§ interstitial fluid
(ISF, surrounds all cells) Intravascular
Interstitial fluid
§ intravascular fluid
fluid
(in plasma in the vascular/ circulatory
system)
Cell

Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed. Philadelphia: Elsevier Saunders; 2005.

5
The body’s fluid compartments

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 Body fluid distribution
70kg
TOTAL BODY FLUID
42 litres
60% of total body weight

Intracellular fluid (ICF) Extracellular fluid (ECF)

28 litres 14 litres
40% of body weight 20% of body weight

Intravascular fluid Interstitial fluid

3 litres 11 litres

Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed. Philadelphia: Elsevier Saunders; 2005.

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 Composition of body fluids
All body fluids are dilute solutions of water (solvent) and dissolved substances (solutes)1

Intravascular fluid Interstitial fluid

Membrane
Na+
CI–
Protein Electrolytes
• Solutes can be electrolytes
(electrically charged) or Magnesium
non-electrolytes1 CI– Protein Na+ Sodium
PO43–
K+ Chloride
Protein Potassium
Mg2+
• The major solutes are present PO43–

in all fluids but in differing Protein Phosphate

HCO3–
K+
quantities2 HCO3– Bicarbonate
Mg2+ Calcium
Ca2+
Ca2+

1. I.V. Therapy Made Incredibly Easy. 4th ed. Lippincott Williams & Wilkins; 2009.
2. Bianchetti MG, et al. Ital J Pediatr 2009;35:36.
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Fluid spaces of the body

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Composition of the body compartments.

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 Indications for IV fluid therapy
Required where patient is incapable of taking fluid by other means or where rapid effects
are required

A wide range of conditions require treatment with IV

fluids following fluid and blood loss, including:
Trauma Vomiting Uncontrolled diabetes Excess diuretics

Surgery Diarrhoea Renal failure Fractures

Burns Sweating Infection Septicaemia

Haemorrhage Hypoxia Peritoneal irritation Shock

Fluids & Electrolytes Made Incredibly Easy. 4th ed. Lippincott Williams & Wilkins; 2009.
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 Movement of fluid: osmosis
Osmosis is the movement of water across a
semi-permeable membrane

Solution
Semipermeable containing • From an area of lower solute
membrane a solute Increase in
volume due to concentration to one of higher solute
osmosis
concentration

• Osmosis stops when the

concentration on both sides of the
membrane is equal

• Fluid and some small molecules pass

freely but proteins do not

Change in liquid level due to osmosis

Fluids & Electrolytes Made Incredibly Easy. 4th ed. Lippincott Williams & Wilkins; 2009.

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 Effect of fluid movement in Red Blood Cells

http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__how_osmosis_works.html

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 Assessment of fluid balance

The concentration of solutes in body fluids is expressed as:

Osmolarity: the number of solute particles in one litre of solution (a mixture of
one or more solutes dissolved in a solvent)1
• Expressed in units of mOsmol/L

Cations & Anions maintain Osmolarity

1. Erstad BL. Pharmacotherapy 2003;23:1085–6. 2. Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed. Philadelphia: Elsevier Saunders; 2005. 3.
Nolan J. Br Med Bull 1999;55:821–43.

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 Plasma constituents

mEq/L Osmolarity

Na+ K+ Ca++ Mg++ CI- Acetate Lactate Gluconate (mOsmol/L)

Plasma2,8 136–145 3.5–5.0 4.4–5.2 1.6–2.4 98–106 Bicarbonate 21–30 280–300

1. Sodium Chloride SmPC, 2010.

2. Powell-Tuck J, et al. British Consensus Guidelines on Intravenous Fluid 4. Ringer's Lactate PI, 2006.
Therapy for Adult Surgical Patients – GIFTASUP. 2011. Available at: 5. Ringer's Acetate PI, 2009.
http://www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf (accessed 6. Ringer's Solution SmPC, 2011.
September 2012). 7. Plasma-Lyte SmPC, 2010.
3. Hartmann's Solution PI, 2005. 8. Kratz A, et al. N Engl J Med 2004;351:1548–63.
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18
 Tonicity of fluids

Tonicity describes the osmotic pressure of solutions relative to each other and to
blood plasma1

• Water will move by osmosis from the hypotonic solution

(lower concentration) to the hypertonic solution
• IV solutions may be classified in three ways
according to their tonicity
1. Isotonic: same osmolarity as plasma (e.g.
Sodium Chloride 0.9%, Plasmalyte)
2. Hypotonic: osmolarity is less than plasma
(e.g. Sodium Chloride 0.45%,
154 mOsm/L, Ringer lactate)
3. Hypertonic: osmolarity is higher than
plasma (e.g. Sodium Chloride 3%,
1025 mOsm/L)

1. I.V. Therapy Made Incredibly Easy. 4th ed. Lippincott Williams & Wilkins; 2009.

For Baxter Internal Use Only. 2012-10-10 MD-IV-203

Osmolarity & tonicity: what’s the difference?
Osmolarity Tonicity
Measure of osmotic pressure of a Refers to relative concentration of
solution electrolytes (solute particles) inside a
cell with respect to concentration
outside the cell

Both penetrating as well as A state created by non-penetrating

non-penetrating solute molecules solute only
are taken into consideration

à another way of expressing the à tonicity is effective osmotic

concentration of a solution pressure

Bianchetti MG, et al. Ital J Pediatr 2009;35:36.

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20
 Key take home points

• Concentration of solutes in body fluids is expressed

as osmolarity

• Osmosis – movement of water across a semi-

permeable membrane from a low solute concentration
to a high solute concentration

• Isotonic Fluids: Plasmalyte, 0.9% Normal saline

• Hypotonic Fluids: Ringer’s lactate

21
Stewart: Strong Ion Difference

SIMPLIFYING ignoring minor effects of plasma

protein (ATOT):

SID is the major determinant of

plasma pH
Na+, K+, Cl- are strong ions
SID » Na++ K+ - Cl-

Stewart PA Modern quantitative acid-base chemistry

Can J Physiol Pharmacol 1983;61:1444-61
Physiological solutions (those causing
neither acidosis nor alkalosis) require
SID approximately 40-42 mEq/L

Story D and others Qualitative physical chemistry analysis

of acid-base disorders in critically ill patients
Anaesthesia 2001;56:530-533
q SID of NaCl 0.9%:SID = 154 Na+ – 154 Cl- = 0
mEq/L

q SID of RL =SID (131 Na++ 4 K+) – (111 Cl-) =

24 mEq/L

q SID of Plasmalyte = SID (140 Na++ 5 K+) – (98

Cl-) = 47 mEq/L

Morgan TJ and others. Crystalloid strong ion difference determines metabolic acid-base change during in
vitro hemodilution Crit Care Med 2002;30(1):157-160
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Which fluids are in use?
Fluid Therapy& specific treatments

Colloids Crystalloids Other fluids

Dextran
Glucose 5%
Electrolyte solutions like:
Albumin
Mannitol
NaCl 0.9%/ 0,45%
Gelatin

Ringer’s solution
Electrolyte concentrates

HES Lactated Ringer’s

(Hydroxyethyl starch)
Plasmalyte/
etc.
sterofundin
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Evolution of Crystalloids

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 Plasma-Lyte profile is closer to normal plasma than several
commonly-used solutions1

mEq/L Osmolarity

Cations Anions

Na+ K+ Ca++ Mg++ CI- Acetate Lactate Gluconate (mOsmol/L)

NaCI 0.9%1 154 – – – 154 – – – 309

Hartmann's Solution2,3 131 5.0 4.0 – 112 – 28 – 275

Ringer's Lactate4 130 4.0 3.0 – 109 - 28 – 273

Ringer's Acetate5 130 4.0 4.0 2.0 110 30 – – 277

Stereofundin
(pH 5.1)
145 4.0 2.5 1.0 127 24 - Malate 5.0 309

Plasma-Lyte A
140 5.0 0 3.0 98 27 – 23 295
(pH 7.4)

Plasma2,8 136–145 3.5–5.0 4.4–5.2 1.6–2.4 98–106 Bicarbonate 21–30 280–300

28
 mEq/L Osmolarity

Cations Anions

Na+ K+ Ca++ Mg++ CI- Acetate Lactate Gluconate (mOsmol/L)

NaCI 0.9%1 154 – – – 154 – – – 309

Hartmann's Solution2,3 131 5.0 4.0 – 112 – 28 – 275

Ringer's Lactate4 130 4.0 3.0 – 109 - 28 – 273

Ringer's Acetate5 130 4.0 4.0 2.0 110 30 – – 277

Stereofundin
(pH 5.1)
145 4.0 2.5 1.0 127 24 - Malate 5.0 309

Plasma-Lyte A
140 5.0 0 3.0 98 27 – 23 295
(pH 7.4)

Plasma2,8 136–145 3.5–5.0 4.4–5.2 1.6–2.4 98–106 Bicarbonate 21–30 280–300

29
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How do various crystalloid IV solutions
compare with plasma?
Ringer's Lactate solution1
• Hypotonic relative to plasma, containing lower sodium levels than plasma
• Contains lactate which needs a functioning liver to convert to bicarbonate
• Contains calcium so cannot be co-administered with some blood products containing citrate

Sodium Chloride (saline)1,2

• Contains high chloride (154 mEq/L), can lead to hyperchloraemic acidosis
• Can lead to acid–base disturbances and renal vasoconstriction – this can be misinterpreted
as worsening perfusion, leading to more infusion
• Can lead to fluid overload, oedema and worsening acidosis

Plasma-Lyte 148 (pH 7.4)3

• Physiologically balanced, containing sodium, potassium, magnesium and chloride but no
calcium
• Contains the bicarbonate precursors, acetate and gluconate

1. Zander R. EJHP Practice 2006;12:60–2. 2. Mathes DD, et al. Anesthesiology 1997;86:501–3. 3. Plasma-Lyte SmPC, 2010.

34
Causes of metabolic acidosis

Metabolic acidosis has many causes1,2

• Lactic acidosis
• Hyperchloraemic metabolic acidosis (HCMA)

The acid-base balance in body fluids is a factor in

selection of replacement fluids

• Some IV fluids (such as 0.9% Normal Saline) do not contain

substances that can replace bicarbonate3.

1. Merck Manual Professional. Metabolic acidosis. 2008. 2. Cocchi MN, et al. Emerg Med Clin N Am 2007;25:623-42.
3. Zander R. EJHP Practice 2006;6:60–2. 4. Scheingraber S. et al. Anesthesiology 1999;90:1265–70.

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35
 Acetate Gluconate Lactate Malate

Onset of action Slow, longer duration

(Bicarbonate Rapid (15 min) Delayed Delayed
production)

Bicarbonate 1 mole 1 mole 1 mole 2 mole

production/mole
Acid-base correction
(time of onset) Peaks at 40 min >2.5 hr 2 hrs delayed

>80% eliminated All tissues (muscles)

Metabolism By all tissues unchanged in urine Liver

à Can cause No clinical trial in

Hyperglycemia à (Plasmalyte has been hyperglycemia diabetic patients
studied in DKA without
any evidence of
hyperglycemia)
Starches- Generations

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 Synonyms for HES

• HES 130/0.42 or 130/0.40 is generically

referred to as tetrastarch

• HES 200/0.5 and 250/0.45 are generically

referred to as pentastarch

• HES 450/0.7 is generically referred to as

hetastarch

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Characteristics of HES – Hydroxylethyl starch

• Mean molecular weight (Mw)

• Molar substitution (MS)

• C2/C6 ratio

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 Molecular weight of HES

• Refers to the size and weight of the HES molecule

• e. g. the MW of the HES molecules in Venofundin® varies
from 115,000 to 145,000 Dalton, with mean MW 130,000

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Molar substitution (MS)

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Molar substitution - influence on metabolism/ degradation

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C2 : C6 ratio

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C2 : C6 ratio - influence on metabolism/ degradation

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• 25 countries/single day in 2007
• 1,955 of 5,274 (37.1%) patients received resuscitation fluid

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 The superiority of colloids remain
unproven……

Perel: Cochrane collaboration 2009

• There is no evidence from RCTs that

resuscitation with colloids reduces the
risk of death, compared to resuscitation
with crystalloids, in patients with trauma,
burns or following surgery
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 Recommendation

• We recommend not to use HES with

molecular weight C200 kDa and/or degree
of substitution[0.4 in patients with severe
sepsis (grade 1B) and recommend not to
use these HES solutions in other intensive
care patients with increased risk for AKI
(grade 1C).

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Scandinavian Starch for Severe Sepsis/Septic Shock (6S)
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Crystalloid versus Hydroxyethyl Starch Trial (CHEST)

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Recommendation

• We suggest not to use gelatin in ICU

patients who are at increased risk for
renal failure or bleeding outside the
context of clinical trials
• grade 2C

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Gelatin……?

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 Gelatins……

• Despite over 60 years of clinical

experience with its use, the safety of
gelatin in all settings in which it is used
cannot be reliabl assessed and
confirmed. We suggest the need to
investigate and establish such safety.

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• There is no evidence from RCTs that
resuscitation with colloids reduces the risk of
death, compared to resuscitation with
crystalloids,in patients with trauma, burns or
following surgery.

• As colloids are not associated with an

improvement in survival, and as they are more
expensive than crystalloids, it is hard to see
how their continued use in these patients can
be justified outside the context of RCTs

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Effect on mortality
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 1:1.3
1:1.6
1:1.3
1:1.2

Saline versus Albumin Fluid Evaluation

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The absence of harm is not the
same as
proof of benefit..!!

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 • Conservative strategy of fluid management
improved lung function and shortened the duration
of mechanical ventilation and intensive care without
increasing nonpulmonary-organ failures

Fluids and Catheters Treatment Trial

(FACTT)
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 The 5 Rs Resuscitation

• IV fluids may need to be given urgently to restore

circulation
• Routine maintenance For patients who cannot take oral or
enteral fluids but will have on-going routine requirements
• Replacement Fluids in addition to routine maintenance to
meet existing deficits or on-going losses, such as
insensible losses in fever, GI losses and drain losses
• Redistribution To account for internal fluid distribution,
such as oedema seen in sepsis or liver disease
• The 5 th R Reassessment: a crucial part of IV fluid therapy

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 The clinical principles can be approached as a
series of questions:

1. Does the patient need IV fluid resuscitation?

2. What are the patient’s routine maintenance needs?
3. Can the patient meet fluid and electrolyte needs by
the oral route? 4. Does the patient have existing losses
that need replacement?
5. What is the patient’s current fluid and electrolyte
status?
6. Does the patient have problems with internal
redistribution?
7. What fluid shall I prescribe

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 Standard principles for IV fluid therapy

• Patient’s fluid and electrolyte needs should be

assessed and managed at every ward review
• Skilled and competent professionals should prescribe
and administer IV fluids, and assess and monitor
patients receiving IV fluids
• Therapy should be prescribed with reference to the
“5 Rs”
• IV therapy should be provided as part of a protocol
• Prescriptions must include the type, rate and volume
of fluid to be administered. Fluid and
• electrolyte prescription must be recorded in the IV
fluid management plan for the next 24hours

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 Intravenous Fluids: Do Not Drown in Confusion!

1. Assessment of intravenous fuid need: Only the three major

indications need to be examined thoroughly for the purpose
of a clinical audit: resuscitation; maintenance; and
replacement or redistribution.
2. Clear prescription: Every intravenous uid prescription has
to be detailed to ensure correct administration and that a
uid management plan is available to warrant the continuity of
care.
3. Quality standards: The information in the hospital’s uid
guideline or bundle is used to create different quality
standards.
4. Appropriateness: These standards represent the necessary
elements to do a full and qualitative check of appropriateness

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• Third space is a fiction
• Colloid usage is changing alogside
the evidence base
• Artificial colloids are looking less
and less favourable
• In ICU patients colloids may be
asociated with harm and are more
expensive
• Is this different in perioperative
practice??
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 LCFM

O
S

LGF
FM

R
EA ESS PHASE
E
FLOW PHASE
R
Minutes Hours Days Weeks Time
SAVE

Initial Global
Ischemia Risk of
insult Increased
reperfusion hypoperfuson
Permeability
Syndrome
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