IV FLUIDS IN INTENSIVE CARE

Vineel Bezawada MBBS MS.

 BODY FLUIDS

total volume of body fluids : 60% of lean body weight in men

50% of lean body weight in women.

The volume of whole blood is 6.0 to 6.6% of lean body weight

(or 60 to 66 mL/kg)
which means that only 11 to 12% of the total body fluid volume
is in the intravascular compartment

80-kg Man 60-kg Woman

Total body fluids 48 L 30 L

Whole blood 5.3 L 3.6 L
Plasma 3.2 L 2.2 L
Erythrocytes 2.1 L 1.4 L
 History
In 1861,
Crystalloids passed readily
Thomas Graham's
through the membrane,
investigations on diffusion

whereas colloids did not.

classified
( Greek word - glue)
substances as
crystalloids or colloids
IV fluids are similarly classified
based on their ability to pass
based on their ability to through barriers separating
diffuse through a body fluid compartments,
parchment membrane.
i.e
intravascular and extravascular
(interstitial) fluid compartments
 CRYSTALLOIDS
The principal component of
crystalloids is NaCl.
Na is the most abundant
solute in the ECF.
Because 75 to 80% of the
extracellular fluids are
located in the interstitial
space, a similar proportion of
the total body sodium is in
the interstitial fluids.
Exogenously administered
sodium follows the same
distribution,
so 75 to 80% of the volume
of sodium-based intravenous
fluids are distributed in the
interstitial space.
predominant effect of
volume resuscitation with
crystalloid fluids is to expand
the interstitial volume rather
than the plasma volume.
infusion of 1 L of 0.9% Nacl

adds 275 mL to the Note : the total volume

plasma volume expansion (1100 mL)
slightly greater than the
infused volume.
and
This is the result of a fluid
shift from the ICF to
825 mL to the extracellular space,
interstitial volume
because isotonic saline is
actually hypertonic to the
Plasma
 CRYSTALLOIDS
Dext Na K Cl Acet Lact NH4C Ca Mg HPO Citr Mos
gm/dl l 4 m/lt

5% 50 - - - - - - - - - - 278
D
0.9% - 154 - 154 - - - - - - - 308
NS

5%D, 50 77 - 77 - - - - - - - 432
0.45
% NS

DNS 50 154 - 154 - - - - - - - 586

RL - 130 4 109 - 28 - 3 - - - 274
Isolyt 50 63 17 150 - - 70 - - - - 580
e-G

Isolyt 50 40 35 40 20 - - - - 15 - 410
e-M

Isolyt 50 25 20 22 23 - - - - 3 3 368
e-P

Isolyt 50 140 10 103 47 - - 5 3 - 8 595

e-E
 ISOTONIC SALINE
(0.9% NaCl )

Also called Normal saline. The term is inappropriate

because a one normal (1 N) NaCl solution contains 58 g
NaCl per lt,
whereas isotonic (0.9%) NaCl contains only 9 g NaCl per
liter.
 Disadvantages
isotonic saline has higher concentrations of Na and Cl than
plasma.

it is slightly hypertonic to plasma.

The pH is considerably lower than the plasma pH.

The chloride content is high relative to plasma

(154 mEq/L versus 103 mEq/L, respectively),
so hyperchloremic metabolic acidosis is a potential risk with
large-volume isotonic saline resuscitation.
 LACTATED RINGER'S

Ringer's solution : introduced in 1880 by

Sydney Ringer (UK)
who studied mechanisms
of cardiac contraction .

The solution was designed to promote the contraction of

isolated frog hearts, and contained Ca and K in a sodium
chloride diluent.
 In the 1930s, Alexis Hartmann
(American pediatrician )
proposed the addition of sodium lactate
buffer to Ringer's solution for the
treatment of metabolic acidoses.

The lactated Ringer's solution is also known as Hartmann's

solution
 Advantages
potassium and calcium in concentrations approximate the
free (ionic) concentrations in plasma.

The addition of these cations requires a reduction in sodium

concentration for electrical neutrality,
so lactated Ringer's solution has less sodium than
isotonic saline.

similarly the addition of lactate (28 mEq/L) requires a

reduction in chloride concentration,
the chloride in lactated Ringer's more closely
approximates plasma chloride
 Disadvantages

The calcium in lactated Ringer's can bind to certain drugs

and reduce their bioavailability and efficacy
Eg : Amphoteresin, Ampicillin,
Thiopentone etc.

calcium binding to the citrated anticoagulant in blood

products can inactivate the anticoagulant and promote the
formation of clots in donor blood .

For this reason, lactated Ringer's solution is contraindicated

as a diluent for blood transfusions .

( American association of blod banks,

Technical manual , 1990 ; 368.)
 DEXTROSE SOLUTIONS
(5%,10%,25%,50%)

originally intended to supply nonprotein calories and thus

provide a protein-sparing effect.

5% D : (50 g dextrose per liter) - 170 kcal per liter (3.4 kcal/g
dextrose).

However, total enteral and parenteral nutrition is now the

standard of care for providing daily energy requirements, and
the use of 5% dextrose solutions to provide calories is obsolete.

5% dextrose-in-water solution is not an effective volume

expander.
 Disadvantages

The addition of dextrose increases osmolarity

(50 g of dextrose adds 278 mosm/lt )

when 5% dextrose is added to

RL , Total Osmolality= 525 mOsm/L

or

0.9% NS , Total Osmolality =560 mOsm/L.

 When glucose gets utilized, only water remains,

Distribution :
< 10% remains in Intra vascular space
<30% in Interstitium
and
> 50% in Intra cellular space
- Cellular swelling

If glucose use is impaired (as is common in critically ill

patients), the infused glucose accumulates and creates an
undesirable osmotic force that can promote
- cell dehydration.
 Disadvantages

Lactate Production

The proportion of a glucose load that contributes

to lactate formation
5% in healthy subjects
85% in critically ill patients

Thus, in patients with circulatory compromise,

abnormal glucose metabolism can transform
glucose from a source of useful energy to a
source of toxin production
 Disadvantages

Glucose infusions in critically ill patients :

enhanced CO2 production
(which can be a burden in ventilator-dependent
pts)

Hyperglycemia :

Increased risk of infection,Neuropathy

(VandenBerghe et al, Intensive Insulin Therapy in Critically ill. NEJM,2001;345)

Aggravation of ischemic brain injury

( Sieber et al, Glucose and brain, Crit.Care.Med,1992,20)

Increased mortality
(Finney et al, Glucose control and mortality in critically ill, JAMA,2003;290)
 Many disadvantages in critically ill pts, combined
with a lack of documented benefit,
the recommendation is that

the routine use of 5% dextrose infusions

be abandoned in critically ill patients,
especially for resuscitation.
COLLOIDS
 colloids are large molecules that do not
pass across diffusional barriers as readily as
crystalloids.

Have a greater tendency to stay put and

enhance the plasma volume than do
crystalloid fluids.
 ALBUMIN
Transport protein. Synthesised by liver (10gm / day)

Responsible for 75% of the oncotic pressure of plasma .

Acts as buffer, Antioxidant, transport protein, maintains blood fluidity

by inhibiting platelet aggregation

Heat-treated preparations of human serum albumin are commercially

available as
5% solution (50 g/L)
20% solution (200 g/L)
in an isotonic saline diluent.

Because the accompanying sodium load is small, 20% albumin is also

called salt-poor albumin.
 5% albumin solution
COP = 20 mm Hg

similar in oncotic activity to plasma.

Approximately half of the infused volume of 5% albumin

stays in the vascular space

The oncotic effects of albumin last 12 to 18 hours

 20% albumin solution

COP of 70 mm Hg

expands the plasma volume by 4 to 5 times the volume

infused.

Thus, infusion of 100 mL of 20% albumin can increase the

plasma volume 400 to 500 mL .
This plasma volume expansion occurs at the expense of the
interstitial fluid volume

should not be used for volume resuscitation in hypovolemia.

It is intended for shifting fluid from the interstitial space to

the vascular space in hypoproteinemic conditions,
 Complications

Allergic reactions

coagulopathies - most are dilutional and not accompanied

by bleeding

Because albumin preparations are heat-treated,

there is no risk of viral transmission (including human
immunodeficiency virus).
Safety
of
ALBUMI
N
 Cochrane Injuries Group AlbuminReviewers
BMJ 1998;317:235-240 (25July)

Design: Systematic review of randomised controlled trials

comparing albumin or plasma protein fraction or crystalloid
solution in critically ill patients

Subjects: 30randomised controlled trials including

1419randomised patients.

Main outcome measure: Mortality from all causes

 Cochrane Injuries Group
AlbuminReviewers
BMJ 1998;317:235-240 (25July)

Results:

For hypovolaemia the relative risk of death after albumin

administration was 1.46(95% confidence interval 0.97to
2.22)
for burns the relative risk was 2.40(1.11to 5.19)
for hypoalbuminaemia it was 1.69(1.07to 2.67).
Pooled difference in the risk of death with albumin was 6%
(95% confidence interval 3% to 9%)

These data suggest that for every 17critically ill patients

treated with albumin there is one additional death.
 No Increased mortality with
Albumin
Choi et al ,crystalloids vs colloids in fluid
resuscitation, a systematic review , Crit.care.Med.
1999;27

Wilkes et al,Patient survival after human albumin

administration, a metaanalysis of RCTs, Ann Int
Med 2001;135
 SAFE STUDY
A comparison of albumin and saline for fluid resuscitation in
the intensive care unit.
Finfer S, Bellomo R, Boyce N, French J, Myburgh J,
N Engl J Med. 2004 May 27;350(22):2247-56.

a multicenter, randomized, double-blind trial

resuscitation with albumin or saline in a heterogeneous

population of patients in the ICU.

METHODS: patients who had been admitted to the ICU to receive

either 4 percent albumin or normal saline for intravascular-fluid
resuscitation during the next 28 days.

The primary outcome measure was death from any cause during
the 28-day period after randomization.
 SAFE STUDY

RESULTS: Total 6997 patients underwent randomization,

3497 were assigned to receive albumin
3500 to receive saline
the two groups had similar baseline
characteristics.
Mortality :

There were 726 deaths in the albumin group,

and 729 deaths in the saline group
(relative risk of death, 0.99; 95 percent
confidence interval, 0.91 to 1.09; P=0.87).
 SAFE STUDY
New single-organ and multiple-organ failure was similar in
the two groups (P=0.85).
There were no significant differences between
numbers of days spent in the ICU ( P=0.44),
days spent in the hospital P=0.30),
days of mechanical ventilation (P=0.74),
days of renal-replacement therapy ( P=0.41).

CONCLUSIONS: In patients in the ICU, use of either 4

percent albumin or normal saline for fluid resuscitation
results in similar outcomes at 28 days
 Albumin is safe

Vincent et al,
Morbidity in
hospitalised patients
receiving Albumin,
a metaanalysis of
RCTs,
Crit.Care.Med,2004;32
 Current Evidence

Albumin solutions are no more dangerous than

any other colloid or crystalloid solutions.

If adverse effects are evaluated instead of deaths

, Albumin solutions are safer than crystalloid
solutions
 Hydroxyethyl starch
preparations (HES)
Amylopectin - rapidly
hydrolysed
- renally excreted

Hydroxyethyl groups:
- @ C2&C6

metabolic
Degradation

Stored in RES.
 HES
Characteristics :
Concentration
The wt-averaged mean
molecularwt[Mw]
The number- averaged mol wt [Mn]
Molar substitution [MS]
Degree of substitution

Concentration: 3%, 6% and 10%

Molec. wt: low, medium, high
MS : low, moderate, high

The ratio of C2 : C6
hydroxyethylation
pharmacokinetic behaviour,
side effects (eg.Accumulation)
Tetrastarch (Voluven)
6%HES (130/0.4) in isotonic saline sol,
Isooncotic, vol effect approximately 100%
I.V half life 3hrs, Vol stabilization 4-6hrs
blood loss during major surgery
 HETASTARCH

synthetic colloid

available as a 6% solution in isotonic saline.

Contains amylopectin molecules that vary in size from a

few hundred to over a million daltons.
3 types 1. High MW ( 450,000 daltons)
2. Medium MW ( 200,000 daltons)
3. Low MW ( 70,000 daltons )

The High MW Hetastarch has the greatest oncotic activity ,

but also higher adverse events

The main advantage of hetastarch over albumin is its lower

cost
 Features

Hetastarch is slightly more potent than 5% albumin as a

colloid.

It has a higher COP than 5% albumin

(30 versus 20 mm Hg, respectively)

causes a greater plasma volume expansion

(up to 30% greater than the infused volume).

long elimination half-life (17 days)

but
The oncotic effects of hetastarch disappear within 24 hours
 Disadvantages of HES

Hyperamylasemia :

Hetastarch molecules are constantly cleaved by amylase in

the bloodstream before their clearance by the kidneys.

Serum amylase levels are often elevated (2 to 3 times

above normal levels) for the first few days after hetastarch
infusion, and return to normal at 5 to 7 days after fluid
therapy

Anaphylactic reactions : rare (incidence as low as

0.0004%)
 Disadvantages of HES
Coagulopathy :

Inhibition of factor VII,VWF and

impaired platelet adhesiveness

Predominently with High MW Starchs

Absent with Low MW starches

Limited by : infusion < 1500 / 24 hrs

and avoiding in coagulopathy pts

Chronic administration : pruritis

due to extra vascular starch deposits
 PE N TAS TAR CH

A low-molecular-weight-derivative of hetastarch

Available as a 10% solution in isotonic saline.

Not currently approved for clinical use in many countries

Pentastarch contains smaller but more numerous starch

molecules than hetastarch, and thus has a higher colloid
osmotic pressure .

It is more effective as a volume expander than hetastarch.

The oncotic effects dissipate after 12 hours

Less tendency to interact with coagulation proteins than

hetastarch
 Gelatins
Polypeptides

Mol wt 30-35 kDa

Effect on i.v. volume is low

Renal function and haemostasis -

unimpaired.

Anaphylactoid reactions: direct

histamine liberation

Types
Cross linked(eg.Gelofundiol)
Urea linked (eg. Hemaccel)
Succinylated (eg. Gelofusine)
 THE DEXTRANS

Glucose polymers produced by a bacterium

(Leuconostoc) incubated in a sucrose medium.

The two most common dextran preparations are

10% dextran-40 & 6% dextran-70,
both diluted in isotonic saline

Both dextran preparations are hyperoncotic to

plasma
(COP = 40 mm Hg).
Greater increase in plasms volume than
5% albumin or 6% hetastarch

Dextran-70 is the preferred preparation because

of its prolonged action ( 12hrs ) (Dextran-40 : 6
hrs )
 Disadvantages
Bleeding tendency :
by inhibiting platelet aggregation,
reducing activation of Factor VIII
promoting fibrinolysis
Dose-related
Minimized by limiting the daily dextran dose to
20 mL/kg

Anaphylactic reactions :
originally reported in as many as 5%
The current incidence of anaphylaxis is 0.032%
(because of improvements in antigen detection and
desensitization and improvements in preparation purity)
 Disadvantages

Dextrans coat the surface of red blood cells

interfere with the ability to cross-match blood
also increase the erythrocyte sedimentation rate

Acute renal failure

( ? Due to hyperoncotic state with reduced filtration pressure)

(Drumi et al , Dextran-40,Eevated plasma oncotic pressure and acute renal failure,

NEJM1988,318)

However, this mechanism is unproven,

and renal failure occurs only rarely in association with dextran infusions
 COMPOSITION OF COLLOIDS
Colloid Vol. Mol Wt Osm C pH Duration
Effec (kDa) (mOs O of action
t(%) m/kg) P (hr)
5% albumin 100 69 330 19 7.4 24-36
Dextran 40 120 41 255 40 4.0 4-6
Dextran 70 150 70 70 4.0 24
6% Hetastarch 100 69-200 310 30 5.9 24-36

Pentastarch 140 120 308 40 3.5- 18-24

6.5
Gelofusine 80 22.6 274 40 7.2 2-3
Haemaccel 140 35 302 35 7.3 48
 HEXTEND
6% Hetastarch suspended in multielectrolyte solution
instead of isotonic saline

( Na : 143, Cl :125, K :3 , Ca :5,

Mg : 0.9 , Lactate : 28, Glucose : 5 )

Same MW, same starch concentration and equivalent

efficacy as 6% Hetastarch
 HEXTEND

Claimed to have no effect on coagulation and no

hyperchloremic acidosis

Kellum JA: Fluid resuscitation and hyperchloremic acidosis in experimental

sepsis: improved short-term survival and acid-base balance with Hextend
compared with saline. Crit Care Med 30:302-305, 2002

One small study in humans

(Gan et al, Hextend for large volume use in major surgery, Randomized
phase 3 trial, Anesth & Analg,1999;88 )

No strong evidence
 RESUSCITATION
COLLOID
or
CRYSTALLOID
 CRYSTALLOID ORIGINS

The early popularity of crystalloid fluid resuscitation in hypovolemia

stems from two observations made about 40 years ago

Mild hemorrhage - involves a shift of fluid from the interstitial space to

the vascular space.
crystalloid fluids fill primarily the interstitial space

(Moore et al, Effects of haemorrhage on composition,

NEJM,1965;273)

In animal model of hemorrhagic shock,

survival was much improved if a crystalloid fluid was given along with
reinfusion of the shed blood volume .

(Shires et al ,Fluid therapy in hemorrhagic shock, Arch Surg.,1964;88)

 CRYSTALLOID ORIGINS

The combination of these two observations

- interpreted as indicating that the major
consequence of hemorrhage
is an interstitial fluid deficit,

and

replacement of interstitial fluid with crystalloid fluids

is important for survival
 COLLOID PERFORMANCE

The interstitial fluid deficit is predominant

only when blood loss is mild ( < 15% of the blood volume).
In this situation
no volume resuscitation is necessary
(because the body is capable of fully
compensating for the loss of blood volume).

When blood loss is more severe ( >15% )

the priority is to keep the vascular space filled
and thereby support the cardiac output.

colloid fluids are about 3 times more potent than crystalloid fluids for
increasing vascular volume and supporting the cardiac output
 COLLOID PERFORMANCE

colloid fluids are more effective than crystalloid fluids

for volume resuscitation in moderate to severe blood loss
and in patients who are actively bleeding.

Logically the fluid of choice in Hemorrhagic shock

[Crystalloid resuscitation can achieve the same endpoint as

colloid resuscitation, but larger volumes (about 3 times ) must be
used]
 EXPENSE

The biggest disadvantage of colloid

resuscitation is
- the higher cost

Using equivalent volumes of

250 mL for colloid fluids and 1000 mL for
crystalloid
the cost of colloid resuscitation is

3 times as high (if hetastarch is used)

6 times as high (if albumin is used)
than volume resuscitation with isotonic
saline.
Comparative costs of parenteral fluids

Solutions Rs. (INDIA)

Isotonic Crystalloids
0.9% NaCl (500ml) 17
Lactated Ringer's (500ml) 17
Human Albumin
5% albumin (1 U) 2500-4000
25% albumin (1 U) 2500-4000
Colloids (500ml)
3% Hetastarch 175
6% Hetastarch 315
Dextran 40 400
Gelofusine 165
Haemaccel 165
 EDEMA

crystalloids distribute primarily in the interstitial space

- edema

Colloids :
over half of the albumin in the human body is in the
interstitial fluid .
Therefore, a large proportion of infused albumin
eventually finds its way into the interstitial fluid

Edema is also a risk with colloid fluid resuscitation

Especially when capillary permeability is disrupted Eg. Sepsis

Despite this risk, troublesome edema (e.g., pulmonary edema) is

not common with either type of fluid resuscitation when capillary
hydrostatic pressure is not excessive
 SURVIVAL Benefit ?

Despite the superiority for expanding plasma volume,

colloid fluid resuscitation does not confer a higher survival
rate in patients with hypovolemic shock

crystalloids vs colloids in fluid resuscitation, a systematic review , Choi et al

Crit.care.Med. 1999;27

Patient survival after human albumin administration, a metaanalysis of RCTs,

Wilkes et al Ann Int Med 2001;135

A comparison of albumin and saline for fluid resuscitation in the intensive

care unit. SAFE STUDY
Finfer et al, N Engl J Med. 2004 May 27;350(22):2247-56.

Morbidity in hospitalised patients receiving Albumin, a metaanalysis of RCTs,

Vincent et al ,Crit.Care.Med ,2004;32
 HYPERTONIC RESUSCITATION

first report of its successful use in 1980

hypertonic saline has been shown repeatedly to be safe and
effective in the early resuscitation of hypovolemia.

Administration of 250 mL 7.5% NS

- the total volume expansion is 1235 mL
(The volume increments in both fluid compartments is similar to
those produced by 1 L of 5% albumin.)

equivalent volume expansion to colloid fluids with one-fourth the

infused volume

The additional volume comes from intracellular fluid that moves

out of cells and into the ecf.

complications of hypertonic resuscitation: cell dehydration.

 HYPERTONIC RESUSCITATION
Evidence ?

There is little evidence that hypertonic resuscitation is

superior to standard volume resuscitation in Hemorrhagic
shock

(Chiara et al , Resuscitation from hemorrhagic shock, Experimental model

comparing Normal saline, Dextran and Hypertonic saline.
Crit.care.med,2004;31)

No advantage in Prehospital resuscitation of TBI Pts

(Cooper et al, Prehospital Hypertonic resuscitationof patients with

hypotension and traumatic brain injury. JAMA 2004;291)
RESUSCITATION

in

SEPSIS
 SEPSIS Pathophysiology
Intravascular volume depletion

Peripheral vasodilation with hypotension

Abnormal distribution of blood flow

 Aggressive volume resuscitation is
the best initial therapy for the cardiovascular instability of
sepsis
Hypotension can often be reversed with fluid
administration alone

Rackow EC, Astiz ME: Pathophysiology and treatment of septic

shock. JAMA 266, 1991

Ognibene FP: Hemodynamic support during sepsis. Clin Chest Med

17:279, 1996
 Despite sepsis-induced myocardial
depression,
the cardiac index will improve by
25% to 40%
during fluid resuscitation

Packman MJ, Rackow EC: Optimum left heart filling pressure

during resuscitation of patients with hypovolemic and
septic shock. Crit Care Med 11:83, 1983
 Early Goal-Directed Therapy (EGDT)

fluid requirements in severe sepsis and septic shock :

5 L crystalloid in the first 6 hours

and mean of 14 L over the first 72 hours.

Fluid resuscitation is best initiated with

1 to 2 L of 0.9% NaCl

until the serum potassium is available,

followed by 500 mL boluses of lactated Ringer's solution .

Rivers E, Nguyen B, Havstad S, et al: Early goal-directed therapy in the treatment

of severe sepsis and septic shock. N Engl J Med 345, 2001
 Fluid administration should be titrated to clinical end points
such as
MAP
HR
urine output
CVP
Base deficit
SCVO2
serum lactate etc.

In approximately 50% of septic patients who initially present with

hypotension, fluids alone will reverse hypotension and restore
hemodynamic stability.

Marik PE: The assessment of intravascular volume: a comedy of errors. Crit

Care Med 29:1635-1636, 2001.
 choice of IVF
crystalloid or colloid

Remains a controversial issue .

Dellinger RP, Carlet JM, Masur H, et al: Surviving sepsis campaign

guidelines for management of severe sepsis and septic shock.
Crit Care Med 32:858-873, 2004.

Crystalloids have generally been recommended as the

volume expander of first choice

Currently normal saline is the most commonly used

resuscitation fluid in patients with sepsis.
 Normal saline in SEPSIS
large volumes of saline infusion have been shown to
cause
hyperchloremic metabolic acidosis

Kellum JA, Bellomo R, Kramer DJ, et al: Etiology of metabolic acidosis

during saline resuscitation in endotoxemia. Shock 9:364-368, 1998.
Scheingraber S, Rehm M, Sehmisch C, et al: Rapid saline infusion produces
hyperchloremic acidosis in patients undergoing gynecologic surgery.
Anesthesiol 90:1265-1270, 1999.

Rehm M, Orth V, Scheingraber S, et al: Acid-base changes caused by 5%

albumin versus 6% hydroxyethyl starch solution in patients undergoing
acute normovolemic hemodilution: a randomized prospective study.
Anesthesiol 93:1174-1183, 2000.
Kellum JA: Fluid resuscitation and hyperchloremic acidosis in experimental
sepsis: improved short-term survival and acid-base balance with Hextend
compared with saline.
Crit Care Med 30:300-305, 2002
 Do colloids
not cause Metabolic
acidosis ?

After all ,
they also contain Na and Cl
 Acid-base changes caused by 5% albumin versus 6% hydroxyethyl starch
solution in patients undergoing acute normovolemic hemodilution: a randomized
prospective study.
Rehm M, Orth V, Scheingraber
Anesthesiology. 2000 Nov;93(5):1174-83.

CONCLUSIONS :
Preoperative acute normovolemic hemodilution with
5% albumin or 6% hydroxyethyl starch solutions
led to metabolic acidosis.
A dilution of extracellular bicarbonate or changes in strong ion
difference and albumin concentration offer explanations for
this type of acidosis.

hyperchloremic metabolic acidosis and may decrease renal and

splanchnic blood flow
Is hyperchloremic
acidosis SAFE in
SEPSIS ?
 Normal saline induced hyperchloremia in SEPSIS

It may possibly contribute to

increased morbidity and mortality in the critically ill
The hyperchloremia

decrease splanchnic mucosal perfusion

decrease glomerular filtration
and cause coagulopathy

Wilcox CS: Regulation of renal blood flow by plasma chloride.

J Clin Invest 71:726-735, 1983.
Wilkes NJ, Woolf R, Mutch M, et al: The effects of balanced versus saline-based
hetastarch and crystalloid solutions on acid-base and electrolyte status and
gastric mucosal perfusion in elderly surgical patients.
Anesth Analg 93:811-816, 2001.
Ekseth K, Abildgaard L, Vegfors M, et al: The in vitro effects of crystalloids and
colloids on coagulation. Anaesthesia 57:1102-1108, 2002.
 COLLOIDS in SEPSIS

In sepsis
the interstitial volume is increased
due to increase in capillary permeability
and resuscitation with crystalloid solutions
will further increase the interstitial fluid volume

Ernest D, Belzberg AS, Dodek PM: Distribution of normal saline and

5% albumin infusions in septic patients.
Crit Care Med 27:46-50, 1999
 COLLOIDS in SEPSIS
In sepsis,
colloid fluids may be advantageous and may limit the degree of
third space loss

Sibbald WJ, Fox G, Martin CM: Abnormalities of vascular reactivity in sepsis

syndrome. Chest 100[suppl]:S155-159, 1991.

Marik PE, Iglesias J, Maini B: Gastric intramucosal pH changes after volume

replacement with hydroxyethyl starch or crystalloid in patients undergoing
elective abdominal aortic aneurysm repair.
J Intensive Care Med 12:51-55, 1997.

Marik PE, Iglesias J: Would the colloid detractors please sit down!
Crit Care Med 28:2652-2654, 2000.

Albumin and hydroxyethyl starch (HES) solutions are the colloidal

solutions most commonly used in patients with sepsis.
 HES in SEPSIS
HES has a number of theoretical advantages over albumin.

These solutions remain largely intravascular

Maintain osmotic gradient for up to 200 hours postinfusion

Korent VA, Conhaim RL, McGrath AM, et al: Molecular distribution of

hetastarch in plasma and lung lymph of unanesthetized sheep.
Am J Respir Crit Care Med 155:1302-1308, 1997.
 HES in SEPSIS
HES solutions have been demonstrated to have

Antiinflammatory properties
Inhibit endothelial activation and endothelial-associated
coagulation,
resulting in less tissue oedema &
better preserved micro capillary integrity
than crystalloid solutions

Oz MC, Fitz Patrick MF, Zikria BA, et al: Attenuation of microvascular permeability
dysfunction in postischemic striated muscle by hydroxyethyl starch.
Microvasc Res 50:71-79, 1995
Tian J, Lin X, Guan R, et al: The effects of hydroxyethyl starch on lung capillary
permeability in endotoxic rats and possible mechanisms.
Anesth Analg 98:768-774, 2004.
Boldt J, Ducke M, Kumle B, et al: Influence of different volume replacement strategies on
inflammation and endothelial activation in the elderly undergoing major abdominal
surgery.
Intensive Care Med 30:416-422, 2004.
 Albumin in sepsis

In septic patients,

albumin redistributes into the interstitium,

expanding the interstitial volume
equal to the volume of infused albumin

Ernest D, Belzberg AS, Dodek PM:

Distribution of normal saline and 5% albumin infusions in septic
patients.
Crit Care Med 27:46-50, 1999
 Albumin in sepsis
HISTORY :
20th Century

The use of albumin in critically ill patients has

been controversial.

Cochrane Injuries Group AlbuminReviewers

BMJ 1998;317:235-240 (25July)

for every 17critically ill patients treated with

albumin there is one additional death.
 ALBUMIN in 21st
Century
No increased mortality

Choi et al ,crystalloids vs colloids in fluid resuscitation, a systematic

review
Crit.care.Med. 1999;27
Wilkes et al, Patient survival after human albumin administration, a
metaanalysis of RCTs
Ann Int Med 2001;135
Fimfers, Bellomo, A comparison of albumin and saline for fluid
resuscitation in the intensive care unit. SAFE study
N Engl J Med. 2004 May 27;350(22):2247-56
Vincent et al, Morbidity in hospitalised patients receiving Albumin, a
metaanalysis of RCTs,
Crit.Care.Med ,2004;32
 Favorable Futere for Albumin?
Suggestion of SAFE study

4% albumin Vs saline in 6,997 heterogeneous ICU patients

No significant differences between the groups in mortality

In the subgroup of patients with severe sepsis,

the relative risk of 28-day mortality in albumin group as opposed to
saline group was 0.87,
as compared with a corresponding relative risk of 1.05
among patients without severe sepsis (p = 0.06)

Conclusion :
This study provides evidence that albumin is not harmful in
critically ill patients with a suggestion that this volume expander
may be preferable to saline in patients with sepsis.
 Can we use Albumin ?
Recent Metaanalysis
Intern Emerg Med. 2006;1(3):243-5.
Human albumin solution for resuscitation and volume expansion in
critically ill patients. Meta analysis
Liberati A, Moja L, Moschetti I, Gensini GF, Gusinu R.
OBJECTIVES: Effect on mortality of human albumin administration
in critically ill

SEARCH STRATEGY: searched the Cochrane Injuries Group trials

register, Cochrane Central Register of Controlled Trials, Medline,
Embase and BIDS Index to Scientific and Technical PROCEEDINGS:.
The search was last updated in August 2004.

SELECTION CRITERIA: Randomised controlled trials comparing

albumin with a crystalloid solution, in critically ill patients with
hypovolaemia, burns or hypoalbuminaemia.
 MAIN RESULTS:
32 trials , 8452 trial participants

For hypovolaemia, the relative risk of death with albumin was

1.01 (95% CI 0.92-1.10).
This estimate was heavily influenced by the results of the SAFE
trial, which contributed 91% of the information (based on the
weights in the meta-analysis).

For burns, the relative risk was 2.40 ( CI 1.11-5.19)

For hypoalbuminaemia the relative risk was 1.38 (CI 0.94-2.03).

There was no substantial heterogeneity between the trials in the

various categories (chi2 = 21.86, df = 25, p = 0.64).

The pooled relative risk of death with albumin administration was

1.04 ( CI 0.95-1.13).
 For patients with hypovolaemia there is no evidence that albumin
reduces mortality when compared with saline.

There is no evidence that albumin reduces mortality in critically ill

patients with burns and hypoalbuminaemia.

The possibility that there may be highly selected populations of

critically ill patients in which albumin may be indicated remains open
to question.

The review of trials found no evidence that albumin reduces the risk
of dying. Albumin is very expensive in which case it may be better to
use cheaper alternatives such as saline for fluid resuscitation.
How do I
resuscitat
e
Patients
in Septic
shock
Suggested Fluid Resuscitation Algorithm for
Hemodynamic Instability of
Severe Sepsis and Septic Shock

1 L N/S 15-20 minutes

1 L Ringers 30 minutes

Start Norepinephrine if MAP < 70 mm Hg

1 L Hextend/Hespan 30-40 minutes

1 L Ringers 30-40 minutes
1 L Hextend/Hespan 30-40 minutes
Ringers lactate 200cc/h
Bolus 500cc Hextend/Hespan as required

Irwin and Rippe's Intensive Care Medicine,

6th Edition2008
 RESUSCITATION

in

Hemorrhagic shock
 Traditionally :

crystalloids are given initially while awaiting blood products

from the blood bank,
500 mL to 1,000 mL bolus during 15 to 20 minutes and
repeated as necessary.

Certainly by the time 3 L of crystalloid have been used for

resuscitation, blood product replacement should be given
at similar rates of infusion.

All fluids should be infused via a warming device to

alleviate or prevent hypothermia.
 Hypertonic saline (7.5%)
flux of water from the interstitial space and from the cells
to augment the blood volume.

rapid restoration of intravascular volume.

Infusions of small amounts of these solutions lead to

hemodynamic responses equivalent to much larger
volumes of crystalloid solutions.

rapidity of the response

May be used for -Pre hospital resuscitation

Risk of Hypernatremia & Intracellular dehydration

Complications of massive transfusion of
crystalloids or colloids

Dilutional Coagulopathy
Dilutional Anaemia
Edema
Hypothermia
Abdominal compartment Syndrome
SIRS - MODS
Rhee P, Burris D, Kaufmann C, et al:
Lactated ringers resuscitation causes neutrophil activation after
hemorrhagic shock. J Trauma 44:313, 1998 .
Damage Control
Resuscitation
 Damage Control Resuscitation

Two components:

1. Hypotensive resuscitation

2. Hemostatic resuscitation

. McMullin NR, Holcomb JB, Sondeen J: Hemostatic resuscitation, Yearbook of

Intensive Care and Emergency Medicine 2006. Berlin, Springer-Verlag, 2006,
p 265.

. Hess JR, Holcomb JB, Hoyt DB: Damage control resuscitation: the need for
specific blood products to treat the coagulopathy of trauma. Transfusion
46:685, 2006
 Hypotensive resuscitation :

a military concept that dates from World Wars I and II.

Aim is to maximize the resuscitation benefit to the

mitochondria
while at the same time minimizing rebleeding by not
popping the clot

Hemostatic resuscitation :
Surgical
or Correction of coagulation
 The damage control philosophy focuses on :
restoring normal coagulation
minimizing crystalloid and even initial packed RBC
resuscitation

Both traditional resuscitation products further dilute the already

deficient coagulation factors and can increase multiple organ
failure

Kiraly LN, Differding JA, Enomoto TM, et al: Resuscitation with normal saline (NS) vs.
lactated ringers (LR) modulates hypercoagulability and leads to increased blood loss
in an uncontrolled hemorrhagic shock swine model. J Trauma 61:57, 2006.

Todd AR, Malinoski D, Muller PJ, et al: Hextend attenuates hypercoagulability after
severe liver injury in swine. J Trauma 59:589, 2005.

Alam HB, Stanton K, Koustova E, et al: Effect of different resuscitation strategies on

neutrophil activation in a swine model of hemorrhagic shock.
Resuscitation 60:91,2004.
Process of Damage Control
Resuscitation

The first element is :

rapid diagnosis and surgical control of named vessels and

gauze packing (standard damage control surgery)
Damage control surgery has improved outcomes in
severely injured trauma patients
Holcomb JB, Hirshberg A, Helling TS:
Military, civilian, and rural application of the damage control philosophy.
Milit Med 166:490, 2001.

Second is early (in the ED) use of rFVIIa - if INR is

abnormal
 rFVIIa in Hemorrhagic sock

early administration of rFVIIa decreased packed RBC use by

23%

Animals treated with rFVIIa demonstrated an increase in

the systolic blood pressure at which arterial rebleeding
occurs, suggesting the formation of a tighter, stronger fibrin
plug in the presence of high concentrations of rFVIIa

Sondeen JL, Pusateri AE, Hedner U, et al:

Recombinant factor VIIa increases the pressure at which rebleeding occurs
in porcine uncontrolled aortic hemorrhage model.
Shock. 22:163, 2004.
 rFVIIa in Hemorrhagic sock

Seven prospective, randomized surgical trials have

documented the safety of this drug
including one prospective randomized trauma study

Boffard K, Riou B, Warren B, et al: Recombinant factor VIIa as

adjunctive therapy for bleeding control in severely injured trauma
patients: two parallel randomized, placebo-controlled, double-
blind clinical trials. J Trauma 59:8, 2005

Many case reports relate clinical descriptions of efficacy

 rFVIIa in Hemorrhagic sock

The clinical goal is

a subnormal prothrombin time or INR
ensuring that if bleeding is still occurring
then surgical intervention is required

McMullin NR, Kauvar DS, Currier HM, et al:

The clinical and laboratory response to recombinant factor viia in
trauma and surgical patients with acquired coagulopathy.
Curr Surg 59:8, 2006.
 Optimal fluid in Hemorrhagic shock

Fresh Whole Blood (FWB) is the optimal resuscitation fluid

for hemorrhagic shock

Barbee RW, Kline JA, Watts JA: A comparison of resuscitation with packed
red blood cells and whole blood following hemorrhagic shock in canines.
Shock 12:449, 1999

Other crystalloids and colloids cause significant neutrophil

activation, which is not seen with FWB resuscitation.

FWB resuscitation improves the coagulation status of

combat casualties
Spinella PC, Grathwohl K, Holcomb JB, et al: Fresh warm whole blood use
during combat. Crit Care Med 33:146S, 2006.
 Mixture of
one packed RBC unit (335 mL) with a hematocrit of 55%,
one unit of platelet concentrate (50 mL) with 5.5* 1010platelets
and one unit of FFP (275 mL) with 80% coagulation factor activity.
This combination results in 660 mL of fluid with a hematocrit of 29%,
88,000 platelets per L, and 65% coagulation factor activity

A 500-mL unit of FWB has

a hematocrit of 38% to 50%,
150,000 to 400,000 platelets per L,
and 100% activity of clotting factors
diluted only by the 70 mL of anticoagulant

Armand R, Hess JR: Treating coagulopathy in trauma patients.

Transfus Med Rev 17:223, 2003.
 In addition, the viability and flow characteristics of fresh RBC are
better than their stored counterparts that have undergone
metabolic depletion and membrane loss.

FWB has been demonstrated to reverse dilutional coagulopathy

a single unit of FWB has a hemostatic effect

similar to 10 units of platelets

Lozano ML, Rivera J, Gonzalez-Conejero R, et al: Loss of high-affinity

thrombin receptors during platelet concentrate storage impairs the
reactivity of platelets to thrombin. Transfusion 37:368, 1997.

Mohr R, Goor DA, Yellin A, et al: Fresh blood units contain large potent
platelets that improve hemostasis after open heart operations.
Ann Thorac Surg 53:650, 1992
 Indications for rFVIIa

Hypotensive from blood loss (SBP <90 mm Hg)

Have a base deficit >-6
Hypothermic ( <96F)
Coagulopathic (clinically or an INR >1.5)
Have a Hgb <11
Have weak or absent radial pulse character
Have more than one major amputation
Have major truncal injury with a positive FAST examination
Abnormal mental status from trauma or CT scan with
intracranial injury
Have >1,000 mL immediately out of a chest tube or >200
mL h
Anticipated and actual transfusion of >four units of PRBCs
Require damage control maneuvers
Require fresh whole blood
Guidelines for administration of rFVIIa

rFVIIa at dose of 90-120 mcg/kg IV push.

If coagulopathic bleeding continues 20 minutes after infusion
. Administer two additional units fresh whole blood
or
4 units FFP, 10 packs of cryoprecipitate and 6 packs of
platelets
. Redose rFVIa 90-120 mcg/kg IV push.

Administration limits
. Four doses (typically 12 vials) within a 6-h period.

. If bleeding persists after four doses ,Consult the senior

surgeon before administering more rFVIIa.
Best IV Fluid for Rsuscitation in
ICU
 Optimal IV Fluids for SHOCK in
ICU

SEPSIS :
HYPOVOLEMIA :
CRYSTALLOIDS &
CRYSTALLOIDS COLLOIDS

HEMORRHAGE :

CRYSTALLOIDS,
FWB